Sentinel lymph node status in vulval cancer: systematic reviews of test accuracy and decision-analytic model-based economic evaluation.

BACKGROUND: Vulval cancer causes 3-5% of all gynaecological malignancies and requires surgical removal and inguinofemoral lymphadenectomy (IFL). Complications affect > 50% of patients, including groin wound infection, lymphoedema and cellulitis. A sentinel lymph node (SLN) is the first groin node with the highest probability of malignancy. SLN biopsy would be useful if it could accurately identify patients in whom cancer has spread to the groin, without removing all groin nodes. SLNs can be identified by isosulfan blue dye and/or technetium-99 ((99m)Tc) radioactive tracer during lymphoscintigraphy. The blue dye/(99m)Tc procedure only detects SLN, not metastases - this requires histological examination, which can include ultrastaging and staining with conventional haematoxylin and eosin (H&E) or immunohistochemistry. OBJECTIVES: To determine the test accuracy and cost-effectiveness of the SLN biopsy with (99m)Tc and/or blue dye compared with IFL or clinical follow-up for test negatives in vulval cancer, through systematic reviews and economic evaluation. DATA SOURCES: Standard medical databases, including MEDLINE, EMBASE, Science Citation Index and The Cochrane Library, medical search gateways, reference lists of review articles and included studies were searched to January 2011. METHODS: For accuracy and effectiveness, standard methods were used and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were to January 2011, with no language restrictions. Meta-analyses were carried out with Meta-Disc version 1.4 (Javier Zamora, Madrid, Spain) for accuracy; none was appropriate for effectiveness. The economic evaluation from a NHS perspective used a decision-tree model in DATA TreeAge Pro Healthcare 2001 (TreeAge Software, Inc., Williamstown, MA, USA). Six options (blue dye with H&E, blue dye with ultrastaging, (99m)Tc with H&E, (99m)Tc with ultrastaging, blue dye/(99m)Tc with H&E, blue dye/(99m)Tc with ultrastaging) were compared with IFL. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: For accuracy, of the 26 included studies, most evaluated (99m)Tc/blue dye combined. Four studies had clinical follow-up only for test negatives and five had clinical follow-up for all and IFL for test negatives. Numbers with no SLN found were difficult to distinguish from those with negative SLN biopsies. The largest group of 11 studies using (99m)Tc/blue dye, ultrastaging and immunohistochemistry had a pooled sensitivity of 95.6% [95% confidence interval (CI) 91.5% to 98.1%] and a specificity of 100% (95% CI 99.0% to 100%). Mean SLN detection rates were 94.6% for (99m)Tc, 68.7% for blue dye and 97.7% for both. One study measured global health status quality of life (QoL) and found no difference between SLN biopsy and IFL. One patient preference evaluation showed that 66% preferred IFL rather than a 5% false-negative rate from SLN biopsy. For effectiveness, of 14,038 references, one randomised controlled trial, three case-control studies and 13 case series were found. Approximately 50% died from vulval cancer and 50% from other causes during follow-ups. Recurrences were in the ratio of approximately 4 : 2 : 1 vulval, groin and distant, with more recurrences in node-positive patients. No studies reported QoL. For cost per death averted, IFL was less costly and more effective than strategies using SLN biopsy. For morbidity-free survival and long-term morbidity-free survival, (99m)Tc with ultrastaging was most cost-effective. Strategies with blue dye only and H&E only were never cost-effective. The incremental cost-effectiveness ratio for (99m)Tc with ultrastaging compared with IFL was £4300 per case of morbidity-free survival and £7100 per long-term morbidity-free survival. LIMITATIONS: The main limitations of this study include the lack of good-quality evidence on accuracy, effectiveness and QoL. A large project such as this takes time to publish, so the most recent studies are not included. CONCLUSIONS: A sensitive and specific combined metastatic SLN detection test and information on generic QoL in vulval cancer is urgently required. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Development of an affordable dye-stained microalbuminuria screening test.

BACKGROUND: A simple spot test was developed, which allows quantification of microalbuminuria. Evaluation was carried out according to the ISO 15189 guidelines. METHODS: Urine was spotted on cellulose acetate strips and stained using different sensitive protein binding dyes (nigrosin, Coomassie Blue R-250, amido black). The colour intensity of the stained spots was quantified using a Kodak Image 450 station. RESULTS: Analytical sensitivity of the Coomassie Blue based method (18 mg/L) was better than that for nigrosin (50 mg/ L) or amido black (100 mg/L) based methods. Within-run coefficient of variation (CV) and between-run CV of the Coomassie blue assay were, respectively, 8.4% and 9.7% (50 mg/L), and 3% and 4.5% (400 mg/L). For nigrosin, these data were, respectively, 8.4 and 9.4 (50 mg/L), and 3.4 and 6.4% (400 mg/L). Coomassie Blue showed a preferential binding selectivity towards albumin. The method was found to be linear between 20 and 600 mg/L. A good correlation (r2 = 0.89) was obtained between Coomassie Blue based and immunonephelometric measurements. Immuno-unreactive albumin (prepared by protease treatment) could be detected by the spot test, which offers an advantage of the method versus immunochemical tests. Ammonium sulphate precipitation could further increase the specificity of the assay by eliminating effects of free light chains. CONCLUSION: The described method is very simple and extremely cheap, which makes it potentially suited for screening programmes, particularly in third world countries.

Methylene blue dye as an alternative to isosulfan blue dye for sentinel lymph node localization.

Isosulfan blue dye has been used with increasing frequency in localizing sentinel lymph nodes in breast cancer patients. Few alternative types of dye have been investigated. In a prospective study of 30 patients, methylene blue dye was used instead of isosulfan blue dye to localize the sentinel lymph node. The methylene blue dye localization technique was successful in 90% of patients. These results are similar to those for isosulfan blue dye. This study describes methylene blue dye localization as a successful alternative to isosulfan dye in identifying the sentinel node in breast cancer patients. The methylene blue dye technique offers a substantial cost reduction.

A comparative study on the reliability of the fluorescence microscopy and Ziehl-Neelsen method in the diagnosis of pulmonary tuberculosis.

Pulmonary tuberculosis (PTB) is the most common presentation of tuberculosis (TB) in Kenya. For the diagnosis of PTB the sputum smear is used because it is technically simple, non-invasive and cheap. The reliability of direct smear examination for the diagnosis of TB has however frequently been questioned. To address this problem, a study comparing the reliability of fluorescence microscopy (FM) and Ziehl-Neelsen (ZN) staining method for examination of direct smear in the diagnosis of PTB was carried out at the Respiratory Disease Research Unit Laboratory, Nairobi, Kenya. A total of 1480 sputum specimens collected from patients with suspected PTB were analyzed. Two direct smears were prepared from each specimen, one stained using FM and the other using the ZN method. Culture results were used as the gold standard for assessment. Specificity was 97% and 96% for FM and ZN methods, respectively. The sensitivity of the FM method was 80% and that of the ZN method 65% (p < 0.001). Overall agreement was 86.8%. Positive smears which were missed on the ZN stained smears (15%) contained low density bacilli on both FM stained smears and on culture. The use of FM greatly improves the diagnostic value of the sputum smear especially in patients with a low density of bacilli who are likely to be missed on ZN stained smears. The method is economical in both time and expense and is recommended for laboratories handling large numbers of sputum specimens.