Temporal patterns of hiatus hernia recurrence and hiatal failure: quality of life and recurrence after revision surgery.

Antireflux and paraesophageal hernia repair surgery is increasingly performed and there is an increased requirement for revision hiatus hernia surgery. There are no reports on the changes in types of failures and/or the variations in location of crural defects over time following primary surgery and limited reports on the outcomes of revision surgery. The aim of this study is to report the changes in types of hernia recurrence and location of crural defects following primary surgery, to test our hypothesis of the temporal events leading to hiatal recurrence and aid prevention. Quality of life scores following revision surgery are also reported, in one of the largest and longest follow-up series in revision hiatus surgery. Review of a single-surgeon database of all revision hiatal surgery between 1992 and 2015. The type of recurrence and the location of crural defect were noted intraoperatively. Recurrence was diagnosed on gastroscopy and/or contrast study. Quality of life outcomes were measured using Visick, dysphagia, atypical reflux symptoms, satisfaction scores, and Gastrointestinal Quality of Life Index (GIQLI). Two-hundred eighty four patients (126 male, 158 female), median age 60.8(48.2-69.1), underwent revision hiatal surgery. Median follow-up following primary surgery was 122.8(75.3-180.3) and 91.6(40.5-152.5) months after revision surgery. The most common type of hernia recurrence in the early period after primary surgery was 'telescope'(42.9%), but overall, fundoplication apparatus transhiatal migration was consistently the predominant type of recurrence at 1-3 years (54.3%), 3-5 years (42.5%), 5-10 years (45.1%), and >10 years (44.1%). The location of crural defects changed over duration following primary surgery as anteroposterior defects was most common in the early period (45.5% in <1 year) but decreased over time (30.3% at 1-3 years) while anterior defects increased in the long term with 35.9%, 40%, and 42.2% at 3-5 years, 5-10 years, and >10 years, respectively. Revision surgery intraoperative morbidity was 19.7%, mainly gastric (9.5%) and esophageal (2.1%) perforation. There was a 75% follow-up rate and recurrence following revision surgery was 15.4%(44/284) in unscreened population and 21%(44/212) in screened population. There was no difference in recurrence rate based on size of hiatus hernia at primary surgery, or at revision surgery. There were significant improvements in the Visick score (3.3 vs. 2.4), the modified Dakkak score (23.2 vs. 15.4), the atypical reflux symptom score (23.7 vs. 15.4), and satisfaction scores (0.9 vs. 2.2), but no difference in the various domains (symptom, physical, social, and medical) of the GIQLI scores following revision surgery. Revision hiatal surgery has higher intraoperative morbidity but may achieve adequate long-term satisfaction and quality of life. The most common type of early recurrence following primary surgery is telescoping, and overall is wrap herniation. Anterior crural defects may be strong contributor to late hiatus hernia recurrence. Symptom-specific components of GIQLI, but not the overall GIQLI score, may be required to detect improvements in QOL.

Early experience of tomotherapy-based intensity-modulated radiotherapy for breast cancer treatment.

AIMS: New technology - specifically intensity-modulated radiotherapy (IMRT) - is now being applied to breast radiotherapy and a recent dosimetric analysis confirmed the advantages of IMRT over 'wedge-only' plans. Such application to everyday practice raises new issues and here we present the early experience of IMRT-based breast irradiation in a single centre. MATERIALS AND METHODS: We present cases of breast cancer treated by Tomotherapy-based IMRT, where the perceived advantages of IMRT are considerable. Cases presented are bilateral disease, left breast irradiation, pectus excavatum, prominent contralateral prosthesis and internal mammary chain disease. We discuss the practicalities of such treatment and the advantages over standard breast irradiation techniques. RESULTS: Advantages include better conformity of treatment with lowering of dosages to underlying organs at risk, for example ipsilateral lung and heart. There is improved coverage of the planning target volume, including regional nodes, without field junction problems. Planning, quality assurance and treatment delivery are more time consuming than for standard breast irradiation and the low dose 'bath' is increased. CONCLUSIONS: The standard radiotherapy tangential technique for breast/chest wall treatments has not significantly changed over many decades, whereas across many other tumour sites there have been great advances in radiotherapy technology. The dosimetric advantages of IMRT are readily apparent from our early experience. The wider spread of the lower dose zone (the low dose 'bath' of radiation) is a potential concern regarding late oncogenesis and methods to minimise such risks should be considered.

Fundoplication for laryngopharyngeal reflux despite preoperative dysphagia.

INTRODUCTION Fundoplication for laryngopharyngeal disease with oesophageal dysmotility has led to mixed outcomes. In the presence of preoperative dysphagia and oesophageal dysmotility, this procedure has engendered concern in certain regards. METHODS This paper describes a consecutive series of laryngopharyngeal reflux (LPR) patients with a high frequency of dysmotility. Patients were selected for surgery with 24-hour dual channel pH monitoring, oesophageal manometry and standardised reflux scintigraphy. RESULTS Following careful patient selection, 33 patients underwent fundoplication by laparoscopy. Surgery had high efficacy in symptom control and there was no adverse dysphagia. CONCLUSIONS Evidence of proximal reflux can select a group of patients for good results of fundoplication for atypical symptoms.

Increased oxidative damage to DNA in ALS patients.

Although the cause of amyotrophic lateral sclerosis (ALS) is unknown, substantial evidence indicates that oxidative toxicity is associated with neuronal death in this disease. We examined levels of a well-established marker of oxidative damage to DNA, 8-hydroxy-2'-deoxyguanosine (8OH2'dG) in plasma, urine, and cerebrospinal fluid (CSF) at a single time point from subjects with ALS, other neurological diseases, or no known disorders. We also measured the rate of change of 8OH2'dG levels in plasma and urine from ALS and in urine from control subjects over 9 months and examined the relationship to disease severity. In each fluid, 8OH2'dG levels were significantly elevated in the ALS group as compared to control subjects. In all subjects, the plasma and CSF 8OH2'dG levels increased with age, providing further evidence for a role of oxidative damage in normal aging. Plasma and urine 8OH2'dG levels increased significantly with time in the ALS group only. The rate of increase in urine 8OH2'dG levels with time was significantly correlated with disease severity. These findings are consistent with the hypothesis that oxidative pathology accompanies the neurodegenerative process in ALS and suggest that 8OH2'dG may provide a useful tool for monitoring therapeutic interventions in this disease.

Warfarin-associated hemorrhage and cerebral amyloid angiopathy: a genetic and pathologic study.

BACKGROUND: Intracerebral hemorrhage (ICH) is the most feared complication of warfarin therapy. The pathogenesis of this often-fatal complication remains obscure. Cerebral amyloid angiopathy (CAA) is a major cause of spontaneous lobar hemorrhage in the elderly and is associated with specific alleles of the APOE gene. OBJECTIVE: To assess the role of CAA in warfarin-associated ICH. METHODS: Clinical characteristics and APOE genotype were compared between 41 patients with warfarin-related ICH (from a cohort of 59 consecutive patients aged > or = 65 years with supratentorial ICH on warfarin) and 66 randomly selected individuals aged > or = 65 years without ICH taking warfarin. In addition, all neuropathologic specimens from ICH patients were reviewed for the presence and severity of CAA. RESULTS: Hemorrhages tended to be in the lobar regions of the brain, and most (76%) occurred with an international normalized ratio of < or = 3.0. The APOE epsilon2 allele was overrepresented among patients with warfarin-associated lobar hemorrhage (allele frequency 0.13 versus 0.04 in control subjects; p = 0.031). After controlling for other variables associated with ICH, carriers of the epsilon2 allele had an OR of 3.8 (95% CI, 1.0 to 14.6) for lobar ICH. CAA was pathologically diagnosed as the cause of lobar hemorrhage in 7 of 11 patients with available tissue samples. CONCLUSIONS: CAA is an important cause of warfarin-associated lobar ICH in the elderly. Although diagnosis of CAA before hemorrhage is not yet possible, these data offer hope that future patients at high risk for hemorrhage may be identified before initiation of warfarin therapy.

MRI detection of new hemorrhages: potential marker of progression in cerebral amyloid angiopathy.

The authors used serial gradient-echo MRIs to detect new small hemorrhages in patients with previous lobar hemorrhage. Of 24 lobar hemorrhage patients (17 diagnosed with probable and 7 with possible amyloid angiopathy) who prospectively underwent repeat MRI 1.5 years after initial study, 9 (38%) demonstrated additional hemorrhages at follow-up. Interrater agreement was high. New hemorrhages were more frequent in patients with probable amyloid angiopathy (8 of 17, 47%) with more hemorrhages at baseline (p < 0.01). These results suggest a role for gradient-echo MRI in assessing disease progression in amyloid angiopathy.

Increased CSF F2-isoprostane concentration in probable AD.

OBJECTIVE: To quantify F2-isoprostane levels in CSF obtained from the lumbar cistern of patients with AD, ALS, and controls. BACKGROUND: Studies of human postmortem tissue and experimental models have suggested a role for oxidative damage in the pathogenesis of several neurodegenerative diseases, especially AD and ALS. F2-isoprostanes are exclusive products of free-radical-mediated peroxidation of arachidonic acid that have been widely used as quantitative biomarkers of lipid peroxidation in vivo in humans. Recently, we showed that F2-isoprostane concentrations are significantly elevated in CSF obtained postmortem from the lateral ventricles of patients with definite AD compared with controls. METHODS: F2-isoprostanes were quantified by gas chromatography/negative ion chemical ionization mass spectrometry. RESULTS: CSF F2-isoprostanes were increased significantly in patients with probable AD, but not in ALS patients, compared with controls. CONCLUSIONS: Increased CSF F2-isoprostanes are not an inevitable consequence of neurodegeneration and suggest that increased brain oxidative damage may occur early in the course of AD.

Plasma beta-amyloid peptide, transforming growth factor-beta 1, and risk for cerebral amyloid angiopathy.

Despite the documented association between apolipoprotein E genotype and cerebral amyloid angiopathy (CAA), a substantial proportion of CAA-related hemorrhages occur in patients without known risks for this disorder. Two other factors implicated in the pathogenesis of CAA are the amyloid-beta peptide (preferentially deposited in vessels as a 40-amino acid species) and the multifunctional cytokine transforming growth factor-beta 1 (a specific promoter of vascular amyloid deposition in transgenic models). We measured plasma concentrations of these factors in a series of 25 patients diagnosed with probable or definite CAA-related hemorrhage and compared them with 21 patients with hemorrhage due to probable hypertensive vasculopathy and 42 elderly control subjects without hemorrhage. We found no differences among the groups in concentrations of the 40- or 42-amino acid species of beta-amyloid or either the active or latent form of transforming growth factor-beta 1. While the data do not exclude important roles for these molecules as risks for CAA, they indicate that plasma measurements are not useful in its diagnosis.

Priming reveals attentional modulation of human motion sensitivity.

Although recent fMRI and single unit recording studies have shown that attention modulates neural activity in motion sensitive areas of extrastriate cortex, these approaches cannot reveal qualitative or quantitative effects of attention on perception of motion. To investigate this, we asked observers to select one of two orthogonal directions in a brief, transparent dot display (prime) and then measured their sensitivity to global directional motion in a second uni-directional dot display (probe) presented a short time later. When probe direction matched the attended prime direction, sensitivity was degraded. But, when probe direction matched the ignored prime direction, sensitivity was enhanced, even though both components were of equal physical strength. Sensitivity was unchanged for directions opposite to either previously seen direction. Neither sensory adaptation nor opponent direction mechanisms can account for these data. Rather, processes initiated by visual selection must underlie these dramatic changes in motion sensitivity.

Magnetic resonance imaging with even-echo rephasing sequences in the assessment and management of giant intracranial aneurysms.

The role of magnetic resonance imaging in the assessment of giant intracranial aneurysms was compared with angiography and contrast-enhanced computed tomography (CT) in 18 patients. The use of T1- and T2-weighted spin-echo (SE) sequences demonstrated both the presence and the evolution of thrombus within these lesions. High-velocity flow within the parent vessels and still-patent lumen could be defined as an area of absent signal. The use of even-echo rephasing (EER) sequences provided a rapid technique for demonstrating and confirming the presence of luminal flow, which is shown as areas of high signal. The combination of SE and EER techniques proved superior to CT in the assessment of thrombus and flow patterns in these lesions, as well as enabling superior demonstration of the patency of the parent vessel following surgical ligation. Computed tomography remains the most accurate method of defining the presence and location of associated calcification.

Service user involvement in nurse education: perceptions of mental health nursing students.

Increasingly providers of mental health nurse education are required to demonstrate user involvement in all aspects of these programmes including student selection, programme design and student assessment. There has been limited analysis of how nursing students perceive user involvement in nurse education programmes. The aim of this study has been to explore mental health nursing student's perceptions of involving users in all aspects of pre-registration mental health nursing programme. Researchers completed a number of focus group interviews with 12 ex-mental health nursing students who had been recruited by purposeful sampling. Each focus group interview was recorded and analysed using a series of data reduction, data display and verification methods. The study confirms many of the findings reported in earlier user participation in education studies. Three main themes related to user involvement have been identified: the protection of users, enhanced student learning and the added value benefits associated with user involvement.

An improved method for constructing tissue microarrays from prostate needle biopsy specimens.

BACKGROUND: Prostate cancer diagnosis is routinely made by the histopathological examination of formalin fixed needle biopsy specimens. Frequently this is the only cancer tissue available from the patient for the analysis of diagnostic and prognostic biomarkers. There is, therefore, an urgent need for methods that allow the high-throughput analysis of these biopsy samples using immunohistochemical (IHC) markers and fluorescence in situ hybridisation (FISH) analysis based markers. METHODS: A method that allows the construction of tissue microarrays (TMAs) from diagnostic prostate needle biopsy cores has previously been reported. However, the technique only allows the production of low-density biopsy TMAs with a maximum of 20 cores per TMA. Here two methods are presented that allow the rapid and uniform production of biopsy TMAs containing between 54 and 72 biopsy cores. IHC and FISH techniques were used to detect biomarker status. RESULTS: Biopsy TMAs were constructed from prostate needle biopsy specimens taken from 102 patients entered into an active surveillance trial and 201 patients in a radiotherapy trial. The detection rate for cancer in slices of these biopsy TMAs was 66% and 79% respectively. Slices of a biopsy TMA prepared from biopsies from active surveillance patients were used to detect multiple IHC markers and to score TMPRSS2-ERG fusion status in a FISH-based assay. CONCLUSIONS: The construction of biopsy TMAs provides an effective method for the multiplex analysis of IHC and FISH markers and for their assessment as prognostic biomarkers in the context of clinical trials.

Re-defining rectal volume and DVH for analysis of rectal morbidity risk after radiotherapy for early prostate cancer.

Improved prostate cancer cure rates have been attributed to higher radiotherapy dose prescriptions delivered more safely by modern conformal/intensity-modulated radiotherapy (IMRT) methods. As the dose becomes more concentrated conformally on the prostate, the volume of the rectum "at risk" for damage becomes smaller and more focal on the anterior rectal wall between the upper and lower axial limits of the planning target volume (PTV). The rectal dose-volume histogram (DVH) traditionally studies the whole volume of the rectum, and such definition for "avoidance" planning presupposes that rectal tolerance depends on "whole organ" radiation tolerance (as might, for example, lung or kidney). However, rectal morbidity with modern prostate radiotherapy is determined by anterior rectal wall tolerance between the superior and inferior limits of the PTV; this, we argue, is not dependent on whole organ tolerance. Recent published studies attempting to improve rectal DVH definition have studied the rectal wall only and concluded that rectal wall DVH is more relevant than whole rectum. In this manuscript, it is first demonstrated that a large and more relevant difference exists when comparing whole rectal DVH to "PTV limits" rectal DVH. Secondly, when considering "PTV limits" rectal DVH, the wall vs whole perimeter comparison differs little. Furthermore, by adopting a "PTV limits" DVH, the inferior right quartile of the DVH accurately reflects the dose distribution to the most vulnerable section of the anterior rectal wall. With improving IMRT technologies, scrutiny of this part of the rectal DVH will most accurately predict rectal sparing - reflected in this manuscript by the less precipitous decline of the TomoTherapy DVH vs the three-dimensional conformal DVH towards the maximum dose point received by the rectum.

PET scanning and Gamma Knife radiosurgery in the early diagnosis and salvage "cure" of locally recurrent nasopharyngeal carcinoma.

"Gamma Knife radiosurgery" is high-dose conformal radiation therapy used for the treatment of small target lesions in the head. It is a minimally invasive technique of multiple fixed, precisely aimed cobalt beams, and relies upon strict patient immobilization via a pinned stereotactic frame to deliver treatment to a precisely located target within a coordinated mapping system. This technique has been widely validated for the treatment of intra-cranial neoplasms and arteriovenous malformations. In this manuscript, two cases of early diagnosed, locally recurrent (persistent) nasopharyngeal carcinoma, successfully treated by Gamma Knife, are described. In one of these, early diagnosis by PET scanning may have improved the chance of cure.