A potential biomarker of radiosensitivity in metastatic hormone sensitive prostate cancer patients treated with combination external beam radiotherapy and radium-223.

PURPOSE: The ADRRAD trial reported the safety and feasibility of the combination of external beam radiotherapy and radium-223 in the treatment of de novo bone metastatic prostate. This study aimed to determine if any biomarkers predictive of response to these treatments could be identified. EXPERIMENTAL DESIGN: 30 patients with newly diagnosed bone metastatic hormone sensitive prostate cancer were recruited to the ADRRAD trial. Blood samples were taken pre-treatment, before cycles 2 to 6 of radium-223, and 8 weeks and 6 months after treatment. Mononuclear cells were isolated and DNA damage was assessed at all timepoints. RESULTS: DNA damage was increased in all patients during treatment, with bigger increases in foci observed in patients who relapsed late compared to those who relapsed early. Increases in DNA damage during the radium-223 only cycles of treatment were specifically related to response in these patients. Analysis of hematology counts also showed bigger decreases in red blood cell and hemoglobin counts in patients who experienced later biochemical relapse. CONCLUSIONS: While some patients responded to this combination treatment, others relapsed within one year of treatment initiation. This study identifies a biomarker based approach that may be useful in predicting which patients will respond to treatment, by monitoring both increases in DNA damage above baseline levels in circulating lymphocytes and decreases in red blood cell and hemoglobin counts during treatment.

A novel tool for improving the interpretation of isotope bone scans in metastatic prostate cancer.

OBJECTIVES: The isotope bone scan (IBS) is the gold-standard imaging modality for detecting skeletal metastases as part of prostate cancer staging. However, its clinical utility for assessing skeletal metastatic burden is limited due to the need for subjective interpretation. We designed and tested a novel custom software tool, the Metastatic Bone Scan Tool (MetsBST), aimed at improving interpretation of IBSs, and compared its performance with that of an established software programme. METHODS: We used IBS images from 62 patients diagnosed with prostate cancer and suspected bone metastases to design and implement MetsBST in MATLAB by defining thresholds used to identify the texture and size of metastatic bone lesions. The results of MetsBST were compared with those of the commercially available automated Bone Scan Index (aBSI) with regression analysis. RESULTS: There was strong agreement between the MetsBST and aBSI results (R2 = 0.9189). In a subregional analysis, MetsBST quantified the extent of metastatic disease in multiple bone sites in patients receiving multimodality therapy (radium-223 and external beam radiotherapy) to illustrate the differences in bone metastatic response to different treatments. CONCLUSION: The results of MetsBST and the commercial software aBSI were highly consistent. MetsBST introduces novel clinical utility by its ability to differentiate between the responses of different bone metastases to multimodality therapies. ADVANCES IN KNOWLEDGE: MetsBST reduces the variability in assessment of tumour burden caused by subjective interpretation. Therefore, it is a useful aid to physicians reporting nuclear medicine scans, and may improve decision-making in the treatment of metastatic prostate cancer.

(223)Ra and other bone-targeting radiopharmaceuticals-the translation of radiation biology into clinical practice.

Osseous metastases are a source of significant morbidity for patients with a variety of cancers. Radiotherapy is well established as an effective means of palliating symptoms associated with such metastases. The role of external beam radiotherapy is limited where sites of metastases are numerous and widespread. Low linear energy transfer (LET) radionuclides have been utilized to allow targeted delivery of radiotherapy to disparate sites of disease, with evidence of palliative benefit. More recently, the bone targeting, high LET radionuclide (223)Ra has been shown to not only have a palliative effect but also a survival prolonging effect in metastatic, castration-resistant prostate cancer with bone metastases. This article reviews the different radionuclide-based approaches for targeting bone metastases, with an emphasis on (223)Ra, and key elements of the underlying radiobiology of these that will impact their clinical effectiveness. Consideration is given to the remaining unknowns of both the basic radiobiological and applied clinical effects of (223)Ra as targets for future research.

Congenital cleft foot deformity.

Cleft foot or ectrodactyly is a rare congenital anomaly. It is often associated with cleft hands. Most early authors advised non-operative treatment but more recently surgical treatment has been advised. However the last two decades have seen a trend towards surgical management of these deformities. Most authors agree that whilst cosmesis is an important consideration, the main aim of correction is to provide feet which could fit into normal shoes and to provide or maintain a normal functional foot. We describe our experience with five feet in three patients treated surgically as a one step procedure as opposed to a staged approach.

The effect of trainee involvement on procedure and list times: A statistical analysis with discussion of current issues affecting orthopaedic training in UK.

INTRODUCTION: Training surgeons adds time to the duration of procedures and operation lists. This is not accounted for in the finance received to perform the operation by the hospital in the Payment by Results (PbR) system. PURPOSE OF THE STUDY: To find out: 1. The effect on the duration of a procedure and the number of procedures performed on the list when a trainee is involved. 2. The percentage of orthopaedic cases with trainee involvement. 3. The effect of European working time directive (EWTD) on the trainee involvement in cases from theatre data in 2008 versus logbook data from 2004 - 2008. METHODS: Data was taken from two different sources. Firstly, the Operating Room Information System (ORMIS) and patient operation notes. The second source was a consultant's logbook comprising 227 primary total knee replacements performed between 2004 and 2008. RESULTS: The data produced trends suggesting trainees took longer to perform procedures than consultants. In orthopaedic operations, 92% of cases had trainees present and of these 17% of cases were performed by trainees in 2008. Before the implementation of the EWTD, trainees performed more procedures when compared with current logbook data (38% versus 17% cases). Time taken by a trainee to perform the procedure under direct consultant supervision was significantly higher in comparison to procedures performed by a consultant alone (P = < 0.0001). Analysing the ORMIS and logbook data gave similar conclusions. DISCUSSION & CONCLUSION: Hospitals should be given financial recognition for training. In this debate, we should remain focused on the provision of quality training for the next generation of surgeons.

Portable mass spectrometry for measurement of anaesthetic agents and methane in respiratory gases.

Monitoring the composition of gases breathed by anaesthetised patients requires measurement methods with fast responses, high accuracy and good reliability. There is also an increasing demand for systems to be able to monitor more than one target analyte simultaneously, but some gas analysers can be sensitive to the presence of methane gas in exhaled breath, consequently leading to inaccurate measurements of the anaesthetic agent. This study investigated the feasibility of employing portable quadrupole mass spectrometry to monitor volatile anaesthetic agents (halothane, isoflurane and sevoflurane), methane accumulation in anaesthetic rebreathing systems, and inspired and exhaled carbon dioxide and oxygen concentrations during equine anaesthesia in a clinical setting. The volatile anaesthetic agents were easily measurable and methane was detectable. The instrument had an advantage over short wavelength infrared absorption spectrometry analysers because it could monitor anaesthetic agents and other respiratory gases simultaneously and at extremely low concentrations, although further optimisation is required.

Sporting and physical activity following Oxford medial unicompartmental knee arthroplasty.

The purpose of this study was to evaluate and assess the sporting and physical activities of patients who had undergone an Oxford medial unicompartmental knee arthroplasty (UKA). Seventy-six patients who underwent a UKA between 2000 and 2003 were reviewed. Demographic data such as age, sex and comorbidities were recorded. University of California Los Angeles (UCLA) activity level ratings and Oxford knee scores were determined for each patient. The sporting and physical activities of all patients' pre- and post-operatively were recorded. The mean age of patients was 64 years (range 49-81) at surgery and 66 years (range 53-82) at review. The mean follow up time was 18 months (range 4-46). Following surgery there was a significant improvement in UCLA activity level scores from 4.2 to 6.5 (Wilcoxon Matched-pairs Signed-rank Test, p<0.01). Forty-two patients (64%) regularly participated in sport before they became symptomatic with significant knee pain, and thirty-nine patients (59%) regularly participated in sports after surgery. In total 93% of patients successfully returned to their regular sporting and physical activities following surgery. The published long-term survivorship of the Oxford UKA has given surgeons increasing confidence to use the prosthesis on a younger generation of patients. Our study has demonstrated that this population of patients is extremely active. A more detailed study is required to evaluate the long-term effects of sporting activity on the Oxford UKA.

Changes in arthroscopic findings in the anterior cruciate ligament deficient knee prior to reconstructive surgery.

We retrospectively compared the arthroscopic findings of 75 patients at the time of diagnosis of ACL rupture and the findings at the time of ACL reconstruction. We found that in the ACL deficient knee the deterioration in meniscal tears and osteochondral lesions was statistically greater with increased interval between diagnosis of ACL rupture and reconstruction. This study implies that in those patients where ACL reconstruction is indicated, a delay in reconstructive surgery can have a deleterious effect on the articular surface of the knee.

Postoperative blood loss into plaster casts after clubfoot surgery: an experimental model.

With major surgery in mind, a simple experimental model was used to study the potential blood loss into plaster of Paris casts. Three lower limb models were used to represent a 3-year-old, a 1-year-old, and a 6-month-old. Two thicknesses of plaster were compared in terms of blood volume required to produce staining on the surface of the cast. Whole blood from the laboratory was infused onto the plaster models at various rates. While allowing for the limitations of the model, the blood volume required before staining through the plaster when three plaster rolls were used was an average of 160 mL in the 6-month-old model and 310 mL in the 3-year-old modal, representing 31.4% and 29.5% of total blood volume, respectively. When only two rolls of plaster of Paris were used, an average of 80 mL in the 6-month-old and 180 mL in the 3-year-old model were lost, representing 15.7% and 17% of total blood volume, respectively. This potential blood loss should be borne in mind during major pediatric foot surgery. The use of drains, releasing the tourniquet before wound closure, and casting with two rather than three rolls of plaster are suggested precautions.

Dislocation of the Austin Moore hemiarthroplasty: is closed manipulation justified?

In a retrospective study the outcome of 13 patients who underwent manipulation under anaesthesia (MUA) following dislocation of an Austin Moore hemiarthroplasty was determined. Nine patients died within 4 weeks of an MUA. Seven patients had a successful MUA, two patients without further complication. Six patients had an unsuccessful MUA. Four patients were discharged from hospital. The outcome following MUA of a dislocated uncemented hemiarthroplasty is poor. Subjecting elderly patients to an anaesthetic for a closed manipulation is a procedure of little clinical benefit. We were unable to define any selection criteria to improve the result.

Complications of metalwork removal.

A total of 188 patients who had metalwork removed were reviewed. There was an overall 20 per cent complication rate. The highest complication rate of 42 per cent was seen with forearm fractures. Infection was the most common complication, and was particularly high in those fractures which were originally open (43 per cent) and where infection developed after the initial internal fixation (32 per cent). We suggest using prophylactic antibiotics for these two groups. All nerve injuries were permanent and were produced by junior surgeons.

Group G streptococcal septic arthritis.

The Lancefield group G streptococcus is known to be a cause of serious infective illness. However, few cases of septic arthritis are recorded. Only one report of this infection, following total joint replacement, has appeared in the orthopaedic literature. Here we describe a further case of infection in a previously normal joint that presented with unusual clinical findings and radiographic changes. We stress the importance of accurate bacteriological investigation and aggressive treatment.

Back pain in childhood.

Sixty-one children with back pain presented to the authors' department between 1978 and 1984, accounting for less than 2% of referrals in this age group. Approximately 50% had serious spinal disease, yet clinical findings could be unreliable in distinguishing such patients. In the absence of compelling physical signs, children with normal radiographs, white cell count, and sedimentation rate can be treated symptomatically and observed for some months before more invasive investigations are considered.

The function, pathology, and surgery of the meniscus.

The menisci are vital for normal function of the knee joint and appear to protect the articular surfaces. Meniscal tears are very common, although often they may be asymptomatic. The diagnosis of tears on clinical grounds alone is unreliable, but the advent of arthrography and arthroscopy has made assessment much more accurate. Care should be taken in the ascription of symptoms to minor tears so discovered. The traditional view that meniscal tears cause osteoarthritis is hard to substantiate, and torn menisci may coexist with articular cartilage in excellent condition, whereas grossly degenerate joints may contain amazingly normal menisci. Total meniscectomy is followed by abnormal stress transfer across the joint, and ultimately degenerative changes frequently occur. Partial meniscectomy will relieve mechanical symptoms while preserving a rim capable of some function. Arthroscopic meniscectomy gives excellent results rapidly and is very efficient for both the patient and the surgeon.