Radiotherapy for benign disease; assessing the risk of radiation-induced cancer following exposure to intermediate dose radiation

Most radiotherapy (RT) involves the use of high doses (>50 Gy) to treat malignant disease. However, low to intermediate doses (approximately 3–50 Gy) can provide effective control of a number of benign conditions, ranging from inflammatory/proliferative disorders (e.g. Dupuytren''s disease, heterotopic ossification, keloid scarring, pigmented villonodular synovitis) to benign tumours (e.g. glomus tumours or juvenile nasopharyngeal angiofibromas). Current use in UK RT departments is very variable. This review identifies those benign diseases for which RT provides good control of symptoms with, for the most part, minimal side effects. However, exposure to radiation has the potential to cause a radiation-induced cancer (RIC) many years after treatment. The evidence for the magnitude of this risk comes from many disparate sources and is constrained by the small number of long-term studies in relevant clinical cohorts. This review considers the types of evidence available, i.e. theoretical models, phantom studies, epidemiological studies, long-term follow-up of cancer patients and those treated for benign disease, although many of the latter data pertain to treatments that are no longer used. Informative studies are summarized and considered in relation to the potential for development of a RIC in a range of key tissues (skin, brain etc.). Overall, the evidence suggests that the risks of cancer following RT for benign disease for currently advised protocols are small, especially in older patients. However, the balance of risk vs benefit needs to be considered in younger adults and especially if RT is being considered in adolescents or children.     

Current utility of endoanal ultrasound in the diagnosis of benign proctological disease

Endoanal ultrasound is undoubtedly one of the major advances that has taken place in the evaluation of anorectal disease and pelvic floor disorders in the last decade. The main indications for endoanal ultrasound are evaluation of the morphology of the sphincteric apparatus in patients with fecal incontinence, the localization of perianal abscesses and fistulas, the staging of anal cancer and follow-up of squamous cell carcinoma after conservative treatment, and the study and morphological confirmation of lateral internal sphincterotomy in patients with fissure-in-ano, amongst others. In this article we review the main indications and use of endoanal ultrasound in the diagnosis of benign proctological disease.     

Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring

OBJECT: An intracranial pressure (ICP) monitor, from which cerebral perfusion pressure (CPP) is estimated, is recommended in the care of severe traumatic brain injury (TBI). Nevertheless, optimal ICP and CPP management may not always prevent cerebral ischemia, which adversely influences patient outcome. The authors therefore determined whether the addition of a brain tissue oxygen tension (PO2) monitor in the treatment of TBI was associated with an improved patient outcome. METHODS: Patients with severe TBI (Glasgow Coma Scale [GCS] score < 8) who had been admitted to a Level I trauma center were evaluated as part of a prospective observational database. Patients treated with ICP and brain tissue PO2 monitoring were compared with historical controls matched for age, pathological features, admission GCS score, and Injury Severity Score who had undergone ICP monitoring alone. Therapy in both patient groups was aimed at maintaining an ICP less than 20 mm Hg and a CPP greater than 60 mm Hg. Among patients whose brain tissue PO2 was monitored, oxygenation was maintained at levels greater than 25 mm Hg. Twenty-five patients with a mean age of 44 +/- 14 years were treated using an ICP monitor alone. Twenty-eight patients with a mean age of 38 +/- 18 years underwent brain tissue PO2-directed care. The mean daily ICP and CPP levels were similar in each group. The mortality rate in patients treated using conventional ICP and CPP management was 44%. Patients who also underwent brain tissue PO2 monitoring had a significantly reduced mortality rate of 25% (p < 0.05). CONCLUSIONS: The use of both ICP and brain tissue PO2 monitors and therapy directed at brain tissue PO2 is associated with reduced patient death following severe TBI.     

Results of four-corner arthrodesis using dorsal circular plate fixation

PURPOSE: Four-corner arthrodesis with scaphoid excision has been used to reduce pain and preserve functional range of motion for patients with radioscaphoid arthritis. Early results of 4-corner arthrodesis with scaphoid excision using dorsal circular plate fixation are compared with reported results in the literature. METHODS: We reviewed retrospectively the first 18 four-corner arthrodeses performed with this system by 4 hand surgeons. Two patients had revision surgery for nonunions before the study that were considered failures. Eight patients returned for final radiographs, objective examination, and functional questionnaire. The average follow-up period was 20 months (range, 13-33 mo). These results were compared with reported results in the literature using alternate fixation methods. RESULTS: Radiographic union was achieved in only 3 wrists. Range of motion was 46% that of the opposite normal wrist and grip strength compared with the opposite wrist was 56%. Five patients would have the procedure again and 6 of 8 have returned to their original employment. CONCLUSIONS: Four-corner arthrodesis with scaphoid excision using a circular internal fixation plate produced a high number of nonunions. Grip strength and range of motion results also were inferior to those reported in the literature.     

Psychosocial Evaluation for Bariatric Surgery: The Boston Interview and Opportunities for Intervention

The process of psychosocial evaluation for weight loss surgery (WLS) is one that goes beyond serving the function of information-gathering (Bauchowitz et al. in Surg Obes Relat Dis 3:554–558, 2007; Friedman et al. in Surg Obes Relat Dis 3:376–382, 2007; Lanyon and Maxwell in Obes Surg 17:321–328, 2007; Sogg and Mori in Obes Surg 14:370–380, 2004; Sogg and Mori in Surg Obes Relat Dis 4:455–463, 2008). This process offers myriad opportunities for delivering significant and powerful interventions that can enhance the patient’s success in the WLS process. A discussion of the unique opportunities for psychosocial intervention afforded by the pre-surgical evaluation process is presented, using The Boston Interview for Bariatric Surgery (Sogg and Mori in Surg Obes Relat Dis 4:455–463, 2008) as the organizing framework.     

Open reduction of medial epicondyle fractures: operative tips for technical ease

In the pediatric population, medial humeral epicondylar fractures account for nearly 12% of all elbow fractures. There is ongoing debate about the surgical management of medial epicondyle fracture cases. Our technique in the operative management of medial epicondyle fractures uses the external application of an Esmarch bandage, as well as provisional fixation with needle rather than K-wire fixation. This technique decreases the need for soft-tissue release and, therefore, theoretically, maintains soft-tissue vascularity of the small fracture fragments. Moreover, it preserves the soft-tissue tension medially. It involves the use of a bandage that is universally available in orthopedic operating rooms, including those in developing nations. It is easy to apply by either the principal or assisting surgeon. With practice, it cuts down operative time and can help substitute for an assistant. This relatively simple operative technique makes for a more seamless operative process, improved reduction, and key preservation of soft-tissue vascularity.     

Designing a workplace return-to-work program for occupational low back pain: an intervention mapping approach

Background  

Despite over 2 decades of research, the ability to prevent work-related low back pain (LBP) and disability remains elusive. Recent research suggests that interventions that are focused at the workplace and incorporate the principals of participatory ergonomics and return-to-work (RTW) coordination can improve RTW and reduce disability following a work-related back injury. Workplace interventions or programs to improve RTW are difficult to design and implement given the various individuals and environments involved, each with their own unique circumstances. Intervention mapping provides a framework for designing and implementing complex interventions or programs. The objective of this study is to design a best evidence RTW program for occupational LBP tailored to the Ontario setting using an intervention mapping approach.     

High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats

OBJECT: Ibuprofen is an antiinflammatory drug that disrupts leukocyte-endothelial cell interactions by limiting expression of endothelial adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), also known as CD54. The authors hypothesized that ibuprofen could reduce the size of the infarct associated with transient focal ischemia by inhibition of ICAM-1 expression, and they evaluated its effects in rats treated with middle cerebral artery (MCA) occlusion. Ibuprofen treatment was compared with mild systemic hypothermia, which is known to be neuroprotective and is commonly used during neurosurgical procedures. METHODS: The maximum ibuprofen dose (240 mg/kg/day) that could be tolerated with no systemic toxicity was established in the initial experiments. In the efficacy experiment, rats were pretreated with vehicle, ibuprofen, or hypothermia (33 degrees C) prior to 2 hours of MCA occlusion; then their brains were harvested at 24 hours of reperfusion for histological studies. End-ischemic cerebral blood flow (CBF) was evaluated using [14C]iodoantipyrine autoradiography in additional cohorts. Expression of ICAM-1 within ischemic compared with nonischemic caudate nucleus and putamen (striatum) or cortex was evaluated using immunohistochemical studies. Compared with vehicle treatment, ibuprofen produced a 46.2% reduction (p = 0.01) in striatal infarcts, which was comparable to hypothermia (48.7% reduction, p = 0.02). Ibuprofen did not alter end-ischemic CBF in any region studied, and the ibuprofen treatment group had the lowest proportion of animals with marked ICAM-1 staining. CONCLUSIONS: Ibuprofen given in maximum tolerated doses reduces the striatal infarct size after focal cerebral ischemia. The neuroprotective mechanism does not work through preservation of intraischemic CBF and is consistent with inhibition of ICAM-1 expression; however, at the doses used in this study, other effects of ibuprofen on platelet and endothelial function are possible.     

L-arginine supplementation accelerates renal fibrosis and shortens life span in experimental lupus nephritis

BACKGROUND: Inducible, high-output nitric oxide (NO) production has been identified as a central mediator of cell injury in immune-mediated renal disease. In acute anti-thy-1 glomerulonephritis prefeeding with the NO precursor L-arginine increases mesangial cell injury and the subsequent fibrosis. The present study tested the hypothesis that L-arginine supplementation may also be detrimental in chronic, NO-mediated murine lupus nephritis. METHODS: Groups (N = 18) of female MRL/lpr mice with lupus nephritis were fed the following diets: (1) normal protein (22% casein); (2) normal protein and 1.0% L-arginine in the drinking water; (3) low protein (6% casein); (4) low protein + 0.4%l-arginine; and (5) low protein + 1.0% L-arginine. After 40 days mouse survival, albuminuria, matrix accumulation, inflammatory cell infiltration, immunoglobulin G (IgG) deposition, expression of transforming growth factor-beta 1 (TGF-beta 1), fibronectin and plasminogen activator inhibitor-1 (PAI-1) mRNA and protein, anti-DNA antibody titer, inducible nitric oxide synthase (iNOS) mRNA expression, blood amino acid levels, blood urea nitrogen (BUN) concentrations and blood and urinary NOx (nitrite + nitrate) levels were assessed. RESULTS: L-Arginine supplementation increased mortality significantly (P < 0.02). The death rate increased from 0% in the lowest to 50% in the highest L-arginine intake group (normal protein + 1.0% L-arginine). L-Arginine administration increased albuminuria, renal matrix accumulation, TGF-beta 1, fibronectin, PAI-1, blood L-arginine, L-citrulline, BUN and blood and urine NOx levels, while protein restriction reduced these parameters. Renal cell infiltration and iNOS mRNA expression were decreased in the low protein group only. Anti-ds DNA-IgG and renal IgG deposition were comparable in all groups CONCLUSIONS: Increasing L-arginine intake increases the severity of renal fibrosis and the likelihood of death in MRL/lpr mice. The results appear to be at least in part mediated through enhanced cytotoxic NO generation via iNOS. The data suggest that L-arginine restriction should be considered in human immune-mediated renal diseases.