Laparoscopic removal of a synthetic retropubic mid-urethral sling (tension-free vaginal tape): step-by-step technique.

INTRODUCTION AND HYPOTHESIS: The synthetic mid-urethral sling (MUS) has been the pre-eminent surgical treatment option for stress urinary incontinence (SUI) in women in recent times. However, increasing numbers of patients are now requesting mesh removal, secondary to persisting symptoms attributed to their sling. We present a video demonstrating a combined vaginal and laparoscopic approach to this procedure; along with supporting information outlining essential pre-operative assessment, counselling, and governance considerations. METHODS: A 60-year-old woman presented with a 4-year history of pelvic pain. She ascribed this to her retropubic MUS (a tension-free vaginal tape). Following extensive work-up, the mesh was removed using the technique described. RESULTS: On review, 3 months post-operatively, the patient reported improvement in the vaginal discomfort she had experienced prior to the procedure-albeit with concomitant deterioration in her SUI. CONCLUSIONS: An open or laparoscopic approach can be employed to dissect out the retropubic arms of an MUS. The latter provides a superior view of the retropubic space and confers potential advantages regarding recovery and cosmesis. The surgical technique detailed is safe and effective, especially when augmented by thorough preparation and patient counselling.

Oncocytic lesions of the ocular adnexa: A review of the histopathology with a brief discussion of the pathogenesis.

Oncocytic lesions may be metaplastic, hyperplastic, or neoplastic and occur in a variety of tissues, including those of the ocular adnexa. Oncocytes are enlarged epithelial cells with abundant eosinophilic granules in the cytoplasm, which represent large mitochondria with distorted cristae. The causes of oncocytic lesions remain uncertain, although in some sites such as the lacrimal sac, chronic inflammation may be a factor. Oncocytic neoplasms in all adnexal sites are generally benign (oncocytoma/oncocytic adenoma) and oncocytic adenocarcinomas are uncommon. Research into oncocytic neoplasms, particularly of the kidney and thyroid, has shed some light on the complicated genomic and metabolic changes that are associated with mitochondrial dysfunction in such neoplasms. The major driver event is mutation of mitochondrial DNA-encoding subunits of complex I in the respiratory chain. The subsequent metabolic events may promote tumorigenesis and inhibit malignant transformation. This review discusses the histopathology and histogenesis of two examples of oncocytoma in the ocular adnexa and presents a simplified synopsis of the genomic and metabolic changes that are significant in the pathogenesis of these neoplasms.

Basal cell carcinosarcoma of the eyelid with osteosarcomatous transformation.

A carcinosarcoma is a neoplasm with malignant epithelial and mesenchymal components. It is thought to arise by mesenchymal transformation of the epithelial elements. The cutaneous form of carcinosarcoma is rare and is associated with sun exposure; most cases arise in the head and neck. The epithelial component may be a basal cell carcinoma, a squamous cell carcinoma, or an adnexal carcinoma. The mesenchymal component may be an osteosarcoma, a pleomorphic undifferentiated sarcoma, or another type of sarcoma. Only a few cases of cutaneous carcinosarcoma have been described in the periocular skin. We present a case of basal cell carcinosarcoma with osteosarcoma and pleomorphic undifferentiated sarcoma arising in the lower eyelid of an elderly man.

Evaluation of uncertainties in in situ and ex situ gamma measurements on land areas with low contamination levels.

Previous work on the characterisation of land areas with moderate contamination levels showed that in situ measurements made with a gamma detector can achieve lower levels of the random component of uncertainty than laboratory measurements of extracted samples. This was found when the variance caused by small-scale lateral heterogeneity of contaminants was included in the uncertainty estimation. The present paper documents the results of applying the same techniques of uncertainty estimation to an area with contamination levels that were lower by a factor of 10. If the same counting times were used, it would be expected that both measurement types would be affected by higher levels of random uncertainty in the individual measurements because of increased uncertainty from counting statistics and other factors such as interpretation of gamma spectra. However, when uncertainty due to sampling was included, it was found that both measurements methods were subject to similar combined uncertainties at individual locations. Using an assumption of the depth distributions of radionuclides that was supported by ex situ measurements, in situ measurements were able to produce averaging estimates with an approximate reduction of 50% in the standard error on the mean at ~50% of the cost of the ex situ measurements.

Optimising in situ gamma measurements to identify the presence of radioactive particles in land areas.

High-coverage in situ surveys with gamma detectors are the best means of identifying small hotspots of activity, such as radioactive particles, in land areas. Scanning surveys can produce rapid results, but the probabilities of obtaining false positive or false negative errors are often unknown, and they may not satisfy other criteria such as estimation of mass activity concentrations. An alternative is to use portable gamma-detectors that are set up at a series of locations in a systematic sampling pattern, where any positive measurements are subsequently followed up in order to determine the exact location, extent and nature of the target source. The preliminary survey is typically designed using settings of detector height, measurement spacing and counting time that are based on convenience, rather than using settings that have been calculated to meet requirements. This paper introduces the basis of a repeatable method of setting these parameters at the outset of a survey, for pre-defined probabilities of false positive and false negative errors in locating spatially small radioactive particles in land areas. It is shown that an un-collimated detector is more effective than a collimated detector that might typically be used in the field.

Comparison between in situ and ex situ gamma measurements on land areas within a decommissioning nuclear site: a case study at Dounreay.

Measurements made in situ with gamma detectors and ex situ measurements of soil samples in a laboratory can have complementary roles in the assessment of radioactively contaminated land on decommissioning nuclear sites. Both in situ and ex situ methods were used to characterize (137)Cs contamination within an area at the Dounreay site in Scotland. The systematic difference (bias) between estimates of the mean activity concentration was found to be non-significant when in situ measurements were interpreted using a linear depth model, based on ex situ measurements made at two different depths. An established method of evaluating the random components of measurement uncertainty was used. The random component of analytical uncertainty in the in situ measurements, made in field conditions, was found to exceed that for the ex situ measurements, made in the controlled conditions of a laboratory. However, contamination by the target radionuclide was found to be heterogeneous over small spatial scales. This resulted in significantly higher levels of random sampling uncertainty in individual ex situ measurements. As in situ measurements are substantially less costly, a greater number of measurements can be made, which potentially reduces the uncertainty on the mean. Providing the depth profile of contaminants can be modelled with confidence, this can enable estimates of mean activity concentration over an averaging area to be made with lower overall uncertainties than are possible using ex situ methods.

The determination of urinary free and conjugated cortisol using UPLC-MS/MS.

BACKGROUND: To develop an UPLC-MS/MS method to replace the in-house immunoassay for the analysis of urinary cortisol. RESULTS: Cortisol was extracted from human urine by ethyl acetate and analyzed on a Waters ACQUITY TQD system using a BEH C18 column. Linear calibration curves were generated over the range of 27.6 to 1380 nmol/l and exhibited consistent linearity and reproducibility with a correlation coefficient greater than 0.9950. Intra-day coefficients of variation were between 3.74 and 5.10% and inter-day coefficients of variations were between 4.22 and 6.73%. The extraction recovery of cortisol was greater than 83%. CONCLUSION: An accurate, rapid and robust UPLC-MS/MS method for the determination of urinary cortisol has been developed and validated. With a lower flow rate (0.4 ml/min), a shorter running time per sample and a simple and cost-effective sample preparation, this method is a desirable option for clinical laboratories.

A rapid and accurate UPLC/MS/MS method for the determination of benzodiazepines in human urine.

A rapid, sensitive, and specific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) assay method for simultaneous determination of 13 benzodiazepine compounds in human urine was developed and validated. Aliquots of 0.5 mL of urine specimens were used for the analysis and the benzodiazepines were extracted by single step methanol (containing 0.2% formic acid) precipitation and then separated on a BEH C18 (50 mm × 2.1 mm, 1.7 µm) analytical column with the temperature maintained at 45°C. The mobile phases consisted of methanol and water (both containing 0.2% formic acid) and the flow rate was 0.4 mL/min. The TQ detector, equipped with an electrospray ionization ion source, was set up with a positive mode. The acquisitions were performed in multiple-reaction monitoring (MRM) and the limit of quantification was 20 ng/mL for all of the 13 compounds. The low limits of detections (LODs) of the benzodiazepines in this method were between 0.5 and 2 ng/mL. The chromatographic separation time was 4 min and calibration curves in human urine were generated over the range of 20-2000 ng/mL. The method validation parameters such as accuracy, precision, carryover, recovery, stability, and specificity for all of the 13 compounds were within the acceptable range. This method is suitable for the high throughput screening of benzodiazepines in clinical laboratories.

Therapeutic drug monitoring of clozapine and norclozapine in human serum using ultra-performance liquid chromatography- tandem mass spectrometry.

A rapid, sensitive, and specific method was developed and validated using ultra-performance liquid chromatography- tandem mass spectrometry (UPLC-MS-MS) for simultaneous determination of clozapine and its major metabolite norclozapine in human serum. The compounds were extracted from serum by a single step protein precipitation and analyzed using a UPLC-triple-quadrupole detection (TQD) system. Separation of compounds was achieved on a BEH C18 (50 mm x 2.1 mm, 1.7 microm) analytical column using methanol and water (both containing 0.2% ammonium hydroxide) as the mobile phase at a flow rate of 0.40 mL/min. The compounds were ionized in the electrospray ionization ion source of the TQD and were detected in the multiple reaction monitoring (MRM) mode. The MRM transitions m/z 327 --> 270 and m/z 313 --> 192 for clozapine and norclozapine, respectively, were used for the quantification ions. Clozapine transition 327 --> 192 and norclozapine transition 313 --> 270 were used as confirmation ions. Linear calibration curves in human serum were generated over the range of 10-2000 ng/mL for both clozapine and norclozapine with a correlation coefficient (r(2)) > 0.9970. Calibration curves exhibited consistent linearity and reproducibility. Interassay coefficients of variation (CV) (n = 20) were 3.04-4.94% for clozapine and 2.84-6.07% for norclozapine. Intra-assay CVs (n = 6, 20 days) were 0.61-1.26% and 1.62-2.21% for clozapine and norclozapine, respectively. The extraction recoveries were larger than 95% for both clozapine and norclozapine. The method was applied to the quantification of clozapine and norclozapine in the sera of schizophrenic patients, and the data revealed that the concentrations of two compounds varied significantly in the patients treated with clozapine.