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INTRODUCTION The aim of this study was to determine the clinical significance of focal incidentally detected colorectal abnormalities on 18 F- Fluoro-2-Deoxy-D-Glucose (FDG) PET-CT scans. METHODS Retrospective audit of PET-CT scans performed at our institution between 2009 and 2014. Demographic and clinical details were retrieved from electronic patient records. An advanced adenoma was defined as: ≥1 cm in size, tubullo-villous histology, or displaying high grade dysplasia. A high-risk lesion (HRL) was defined as an advanced adenoma or colorectal cancer (CRC). RESULTS Of the 1911 PET-CT eligible scans, focal incidental colorectal FDG uptake was detected in 99 (5.2%) patients. Colonoscopy was undertaken in 43 (43.4%) patients and 45 FDG-avid sites were evaluated. The commonest site of abnormal FDG uptake was the rectosigmoid region, with 34 (75.6%) of the 45 foci being located in this area. Overall, 23 (53.5%) of these patients had clinically significant pathology. Of the 45 focal PET-CT abnormalities evaluated, 17 (37.8%) were adenomas, of which 11 (24.4%) were advanced adenomas, and six (13.3%) were cancers, with a total of 17 (37.8%) HRLs. Five of the six patients with CRC underwent surgical resection, whilst one had endoscopic resection. The overall survival for the entire cohort was 18 months (range 1-72 months) with those that underwent colonoscopy having higher overall survival compared to those that did not (38 vs. 13.5 months). CONCLUSION Incidental colorectal abnormalities on PET-CT scans are often clinically significant. However, careful selection for colonoscopy is important due to the poor survival in these patients related to the underlying primary malignancy.

Objectives The authors have previously reported on the technical feasibility of subthalamic nucleus deep brain stimulation (STN DBS) under general anesthesia (GA) with microelectrode recording (MER) guidance in Parkinsonian patients who continued dopaminergic therapy until surgery. This paper presents the results of a prospective cohort analysis to verify the outcome of the initial study, and report on wider aspects of clinical outcome and postoperative recovery. Methods All patients in the study group continued dopaminergic therapy until GA was administered. Baseline characteristics, intraoperative neurophysiological markers, and perioperative complications were recorded. Long-term outcome was assessed using selective aspects of the unified Parkinson’s disease rating scale motor score. Immediate postoperative recovery from GA was assessed using the “time needed for extubation” and “total time of recovery.” Data for the “study group” was collected prospectively. Examined variables were compared between the “study group” and “historical control group” who stopped dopaminergic therapy preoperatively. Results The study group, n = 30 (May 2014–Jan 2016), were slightly younger than the “control group,” 60 (51–64) vs. 64 (56–69) years respectively, p = 0.043. Both groups were comparable for the recorded intraoperative neurophysiological parameters; “number of MER tracks”: 60% of the “study group” had single track vs. 58% in the “control” group, p = 1.0. Length of STN MER detected was 9 vs. 7 mm (median) respectively, p = 0.037. A trend towards better recovery from GA in the study group was noted, with shorter “total recovery time”: 60 (50–84) vs. 89 (62–120) min, p = 0.09. Long-term improvement in motor scores and reduction in l-dopa daily equivalent dose were equally comparable between both groups. No cases of dopamine withdrawal or problems with immediate postop dyskinesia were recorded in the “on medications group.” The observed rate of dopamine-withdrawal side effects in the “off-medications” group was 15%. Conclusions The continuation of dopaminergic treatment for patients with PD does not affect the feasibility/outcome of the STN DBS surgery. This strategy appears to reduce the risk of dopamine-withdrawal adverse effects and may improve the recovery in the immediate postoperative period, which would help enhance patients’ perioperative experience.

Microelectrode recording (MER) plays an important role in target refinement in deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson’s disease (PD). Traditionally, patients were operated on in the ‘off-medication’ state to allow intraoperative assessment of the patient response to direct STN stimulation. The development of intraoperative microelectrode recording (MER) has facilitated the introduction of general anaesthesia (GA). However, the routine withdrawal of dopaminergic medications has remained as standard practice. This retrospective review examines the effect of continuing these medications on intraoperative MER for subthalamic DBS insertion under GA and discusses the clinical implication of this approach. Retrospective review of PD patients who had bilateral STN DBS insertion was conducted. A cohort of seven patients (14 STN microelectrodes) between 2012 and 2013, who inadvertently underwent the procedure while ‘on medication’, was identified. This ‘on-medication’ group was compared to all other patients who underwent the same procedure between 2012 and 2013 and had their medications withdrawn preoperatively, the ‘off-medication’ group, n = 26 (52 STN DBS). The primary endpoint was defined as the number of microelectrode tracks required to obtain adequate STN recordings. A second endpoint was the length of MERs that was finally used to guide the DBS lead insertion. The Reduction of the levo-dopa equivalent daily dose (LEDD) was also examined as a surrogate marker for clinical outcome 12 months postoperatively for both groups. For the on-medication group further analysis of the clinical outcome was done relying on the change in the motor examination at 12 months following STN DBS using the following parameters (Hoehn and Yahr scale, the number of waking hours spent in the OFF state as well as the duration of dyskinesia during the ON periods). The on-medication group was statistically comparable in all baseline characteristics to the off-medication group, including age at operation 57 ± 9.9 years vs. 61.5 ± 9.2 years, p = 0.34 (mean ± SD); duration of disease (11.6 ± 5 years vs. 11.3 ± 4 years, p = 0.68); gender F:M ratio (1:6 vs. 9:17, p = 0.40). Both groups had similar PD medication regimes preoperatively expressed as levodopa equivalent daily dose (LEDD) 916 mg (558–1850) vs. 744 mg (525–3591), respectively, p = 0.77. In the on-medication group, all seven patients (14 STN electrodes) had satisfactory STN recording from a single brain track versus 15 out of 26 patients (57.7 %) in the off-medication group, p = 0.06. The length of MER was 4.5 mm (3.0–5.5) in the on-medication group compared to 3.5 mm (3.0–4.5) in the off-medication group, p = 0.16. The percentage of reduction in LEDD postoperatively for the on-medication group was comparable to that in the off-medication group, 62 % versus 58 %, respectively, p > 0.05. All patients in the on-medication group had clinically significant improvement in their PD motor symptoms as assessed by the Hoehn and Yahr scale; the number of hours (of the waking day) spent in the OFF state dropped from 6.9 (±2.3) h to 0.9 (±1.6) h; the duration of dyskinesia during the ON state dropped from 64 % (±13 %) of the ON period to only 7 % (±12 %) at 12 months following STN DBS insertion. STN DBS insertion under GA can be performed without the need to withdraw dompaminergic treatment preoperatively. In this review the inadvertent continuation of medications did not affect the physiological localisation of the STN or the clinical effectiveness of the procedure. The continuation of dopamine therapy is likely to improve the perioperative experience for PD patients, avoid dopamine-withdrawal complications and improve recovery. A prospective study is needed to verify the results of this review

Objectives: Deep brain stimulation for Parkinson’s disease (PD) utilises an implantable pulse generator (IPG) whose finite lifespan in non-rechargeable systems necessitates their periodic replacement. We wish to determine if there is any significant difference in longevity of 2 commonly used IPG systems; the Medtronic Kinetra, and the Medtronic Activa Primary Cell (PC), which has come to replace it. Methods: All patients with bilateral Subthalamic Nucleus stimulators for PD performed in our centre were included. Battery life was then assessed using a Kaplan-Meier approach and comparisons between the Kinetra and Activa PC batteries were performed using log-rank tests. Results: Complete data was available for 183 patients. There was a significant difference in the average battery duration with an estimated median battery life in the Kinetra cohort of 6.6 years (95% CI 6.4–6.7), compared to 4.5 years (95% CI 4.4–4.5) in the Activa PC cohort (p < 0.001). Conclusion: The Activa PC IPG demonstrates a significantly reduced battery life of 2.1 years, with a median battery life of 4.5 years in comparison to 6.6 years in the Kinetra IPG. Future technology developments should therefore be focused on improving the battery life of the newer IPG systems.

Background Battery replacement or revision surgery for neuromodulation implants is conventionally performed using sharp dissection. Meticulous dissection within thick scar tissue is vital to avoid damage to surrounding lead(s), which could result in more extensive revision surgery. Traditional electrosurgery devices are contraindicated as the emitted energy can be transferred to the hardware, resulting in implant or tissue damage with severe consequent complications. Objective We report our experience and potential applications of a novel, pulsed monopolar radiofrequency energy device (PEAK PlasmaBlade, Medtronic PLC, Minneapolis, Minnesota, USA), which facilitates dissection around implants without the risk of damaging or transmitting energy through the system. Methods We conducted a 2-center retrospective study to review the indications, safety, and efficacy of the PlasmaBlade in 57 cases requiring either neuromodulation system replacement or revision. Deep brain stimulator (DBS) battery replacements were undertaken in 45 cases, 8 vagal nerve stimulator battery revisions, 2 intrathecal baclofen system revision, 1 DBS extension revision, and 1 DBS scar revision around the cranial portion of the lead. Results All cases proceeded without adverse event or damage to lead/generator and with a subjective and objective impression of significant time savings. Average operating times for battery replacements were reduced from 37 to 26 minutes (P = 0.015). Conclusion In our experience, the PlasmaBlade is safe to use in revising/replacing neuromodulation implants. We observed no damage or transmission of energy to the implants or leads; additional advantages of the system include reduced operating times, less damage to surrounding tissue, and the potential to facilitate revision procedures in awake patients under local anesthesia.

Context Despite the major risk of regrowth of clinically nonfunctioning pituitary adenomas (CNFAs) after primary treatment, systematic data on the probability of further tumor progression and the effectiveness of management approaches are lacking. Objective To assess the probability of further regrowth(s), predictive factors, and outcomes of management approaches in patients with CNFA diagnosed with adenoma regrowth after primary treatment. Patients, design, and setting Retrospective cohort study of 237 patients with regrown CNFA managed in two UK centers. Results Median follow-up was 5.9 years (range, 0.4 to 37.7 years). The 5-year second regrowth rate was 35.3% (36.2% after surgery; 12.5% after radiotherapy; 12.7% after surgery combined with radiotherapy; 63.4% with monitoring). Of those managed with monitoring, 34.8% eventually were offered intervention. Type of management and sex were risk factors for second regrowth. Among those with second adenoma regrowth, the 5-year third regrowth rate was 26.4% (24.4% after surgery; 0% after radiotherapy; 0% after surgery combined with radiotherapy; 48.3% with monitoring). Overall, patients with a CNFA regrowth had a 4.4% probability of a third regrowth at 5 years and a 10.0% probability at 10 years; type of management of the first regrowth was the only risk factor. Malignant transformation was diagnosed in two patients. Conclusions Patients with regrown CNFA after primary treatment continue to carry considerable risk of tumor progression, necessitating long-term follow-up. Management approach to the regrowth was the major factor determining this risk; monitoring had >60% risk of progression at 5 years, and a substantial number of patients ultimately required intervention.

Summary Background Surgical intervention for advanced Parkinson's disease is an option if medical therapy fails to control symptoms adequately. We aimed to assess whether surgery and best medical therapy improved self-reported quality of life more than best medical therapy alone in patients with advanced Parkinson's disease. Methods The PD SURG trial is an ongoing randomised, open-label trial. At 13 neurosurgical centres in the UK, between November, 2000, and December, 2006, patients with Parkinson's disease that was not adequately controlled by medical therapy were randomly assigned by use of a computerised minimisation procedure to immediate surgery (lesioning or deep brain stimulation at the discretion of the local clinician) and best medical therapy or to best medical therapy alone. Patients were analysed in the treatment group to which they were randomised, irrespective of whether they received their allocated treatment. The primary endpoint was patient self-reported quality of life on the 39-item Parkinson's disease questionnaire (PDQ-39). Changes between baseline and 1 year were compared by use of t tests. This trial is registered with Current Controlled Trials, number ISRCTN34111222. Findings 366 patients were randomly assigned to receive immediate surgery and best medical therapy (183) or best medical therapy alone (183). All patients who had surgery had deep brain stimulation. At 1 year, the mean improvement in PDQ-39 summary index score compared with baseline was 5·0 points in the surgery group and 0·3 points in the medical therapy group (difference −4·7, 95% CI −7·6 to −1·8; p=0·001); the difference in mean change in PDQ-39 score in the mobility domain between the surgery group and the best medical therapy group was −8·9 (95% CI −13·8 to −4·0; p=0·0004), in the activities of daily living domain was −12·4 (−17·3 to −7·5; p

ObjectiveApathy has been reported as a possible adverse effect of deep brain stimulation of the subthalamic nucleus (STN-DBS). We investigated the prevalence and severity of apathy in 22 patients with Parkinson’s disease (PD) who underwent STN-DBS, as well as the effects of apathy on quality of life (QOL).MethodsAll patients were assessed with the Lille Apathy Rating Scale (LARS), the Apathy Scale (AS), and the Parkinson’s Disease Questionnaire and were compared to a control group of 38 patients on pharmacotherapy alone.ResultsThere were no significant differences in the prevalence or severity of apathy between patients who had undergone STN-DBS and those on pharmacotherapy alone. Significant correlations were observed between poorer QOL and degree of apathy, as measured by the LARS (pConclusionOur findings suggest that STN-DBS is not necessarily associated with apathy in the PD population; however, more severe apathy appears to be associated with a higher level of disability due to PD and worse QOL, but no other clinico-demographic characteristics.

Summary Context and Objective Nonfunctioning pituitary adenomas (NFPAs) are the most common subtype of pituitary tumour. Hypopituitarism is observed in NFPAs due to tumour‐ or treatment‐related factors and may increase mortality risk. Here, we analysed the associations of hypopituitarism, hormone replacement and mortality in a large NFPA cohort derived from two large European centres. Design, Setting and Participants Case note review of all patients treated for NFPA in University Hospitals Birmingham and Beaumont Hospital Dublin between 1999 and 2014 was performed. Main Outcome Measures Clinical presentation, treatment strategies, pituitary function and vitality status were recorded in each patient. A multivariate Cox regression model was used to examine the association between hypopituitarism, hormone replacement and premature mortality. Results A total of 519 patients were included in the analysis. Median duration of follow‐up was 7·0 years (0·5–43). A total of 81 deaths were recorded (15·6%). On multivariate analysis, adrenocorticotropic hormone (ACTH) and gonadotropin (Gn) deficiencies were associated with an increased relative risk of death (OR 2·26, 95% CI 1·15–4·47, P = 0·01 and OR 2·56, 95% CI 1·10–5·96, P = 0·01, respectively). Increased hydrocortisone (HC) (P‐trend = 0·02) and lower levothyroxine (LT4) doses (P‐trend = 0·03) were associated with increased risk of death. Mortality increased with the degree of pituitary failure observed (P‐trend = 0·04). Conclusion ACTH and gonadotropin‐deficient patients have higher mortality rates compared to those with intact hormonal axes. Excessive HC and suboptimal LT4 replacement may also increase risk of death. Complex associations between hormone deficiency and replacement underpin the increased mortality risk in NFPA patients.

Object The authors analyze long-term outcome in a substantial number of patients who underwent subthalamic nucleus (STN) deep brain stimulation (DBS) surgery under general anesthesia. Methods Eighty-two patients underwent bilateral placement of DBS electrodes under general anesthesia for advanced Parkinson disease; the STN was the target in all cases. All patients underwent intraoperative microelectrode recording of the STN. No intraoperative macrostimulation was performed. Unified Parkinson's Disease Rating Scale (UPDRS) data were recorded in 28 patients. Assessment of outcome was performed using the UPDRS (in 28 cases), the electrophysiological recordings (in all 82 cases), medication reduction (in 78 cases), and complications (in 82 cases). Results There was improvement in UPDRS scores across all measures following surgery. The total UPDRS score, off medication, improved from 68.78 (geometrical mean, 95% CI 61.76–76.60) preoperatively to 45.89 (geometrical mean, 95% CI 34.86–60.41) at 1 year postoperatively (p = 0.003, data available in 26 patients). Improvements were obtained in UPDRS Part II (Activities of Daily Living) off medication (p = 0.001) and also UPDRS Part III (Motor Examination) off medication (p < 0.001). Results for the on-medication and on-stimulation states also showed a statistically significant improvement for UPDRS Part III (p = 0.047). Good microelectrode recording of the STN was obtained under general anesthesia; the median first-track length was 4.0 mm, and the median number of tracks passed per patient was 3.0. The median reduction in levodopa medication was 58.1% (interquartile range 42.9%–73.3%). One patient had an intracerebral hemorrhage in the track of 1 electrode but did not require surgical evacuation. One patient had generalized convulsive seizures 24 hours postoperatively and was intubated for seizure control. Unified Parkinson's Disease Rating Scale scores were obtained in 26 patients at 1 year, 28 patients at 3 years, 17 at 5 years, and 7 at 7 years postoperatively. Up to 7 years postoperatively, there was sustained improvement in the total UPDRS score. The results in these patients showed minimal deterioration in the motor section of the UPDRS over time, up to 7 years following the operation. The authors found no evidence that the UPDRS Part II scores changed significantly over the period of 1–7 years after surgery (p = 0.671, comparison of mean scores at 1 and 7 years using generalized estimating equations). Conclusions Long-term outcomes confirm that it is both safe and effective to perform STN DBS under general anesthesia. As part of patient choice, this option should be offered to all DBS candidates with advanced Parkinson disease to enable more of these patients to undergo this beneficial surgery.

This paper compares the use of general and local anaesthetic in patients having deep brain stimulator (DBS) surgery. It is a retrospective case note study of 46 patients treated consecutively with subthalamic nucleus stimulation for Parkinson’s disease as practise changed in a Neurosurgical unit. The first 20 patients (LA group) had permanent electrodes placed under local anaesthesia. The remaining 26 patients (GA group) had the entire procedure under general anaesthesia. The groups were similar for age, sex, duration of Parkinson’s disease and preoperative levodopa requirement. The clinical results were similar in that within each group, the reduction in levodopa was not only clinically but also statistically significant (p

Introduction Williams and colleagues reported that DBS surgery for patients with advanced PD improves motor function and quality of life compared to best medical therapy alone at 1 year, but with surgery-related side effects in a minority. This article reports on the economic evaluation alongside this trial. Methods Detailed resource use and quality of life over 12 months after randomization was obtained from the trial reported by Williams and colleagues. Outcomes were measured using the EQ-5D and quality-adjusted life years calculated. Results Year 1 costs for surgery were significantly higher than in best medical therapy, at £19,069 compared to £9,813, a difference of £9,256 (95% confidence interval [CI]: £7,625, £10,887). There was a small, significant gain in utility at 1 year but a statistically insignificant gain of 0.02 quality-adjusted life years (95% CI: −0.015, 0.05) in the surgical arm. The incremental cost per quality-adjusted life year of surgery at 1 year was £468,528. Extrapolation reveals that after 5 years, this ratio is likely to reduce to £45,180, but subsequently rise to £70,537 at 10 years owing to the increased probability of battery replacements (and re-replacements) beyond 5 years. Conclusion In this patient group, DBS is not cost-effective at 1 year. Extrapolation, however, reveals an increasing likelihood of cost-effectiveness up to 5 years and reducing cost-effectiveness between 5 and 10 years. These models are sensitive to assumptions about future costs and quality-adjusted life years gained. © 2016 International Parkinson and Movement Disorder Society

Objective Apathy has been reported as a possible adverse effect of deep brain stimulation of the subthalamic nucleus (STN-DBS). We investigated the prevalence and severity of apathy in 22 patients with Parkinson's disease (PD) who underwent STN-DBS and the effects on quality of life (QOL). Method All patients were assessed with the Lille Apathy Rating Scale (LARS), the Apathy Scale (AS) and the Parkinson's Disease Questionnaire and were compared to a control group of 38 patients on pharmacotherapy alone. The relationship between apathy and clinico-demographic variables was explored through correlation analysis. Results Apathy was reported by a similar proportion of patients in the two groups: 18.4% in the DBS group and 22.7% in the control group according to LARS ratings; 45.5% in the DBS group and 42.1% in the control group according to AS ratings. There was no significant difference in apathy or QOL ratings between the two groups. Significant correlations were observed between poorer QOL and degree of apathy, as measured by the LARS (p

Objectives: To define the role of magnetic resonance imaging (MRI) and intraoperative electrophysiological recording in targeting the subthalamic nucleus (STN) in Parkinson’s disease and to determine accuracy of electrode placement. Patients and methods: We implanted 54 electrodes into the STN in 27 patients. Target planning was done by coordinate guidelines and visualising the STN on MRI and defined in relation to the mid-point of the AC–PC line. Intraoperative microelectrode recording was used. We adjusted electrode positions for placement in the centre of the STN electrical activity and verified this on postoperative MRI in 16 cases, which were fused to the preoperative images to measure actual error in electrode placement in the three axes. Results: Based on coordinate calculation and MRI localisation, the mean of the target was 11.5 mm lateral, 2.5 mm posterior and 4.1 mm inferior to the mid-point of the AC–PC line. Fifty good electrophysiological recordings of the STN (average length 4.65 mm) were achieved and target point adjusted in 90% of lead placements. The mean of the final target after electrophysiological correction was 11.7 mm lateral, 2.1 mm posterior, and 3.8 mm inferior to the mid-point. The distance from the centre of the electrode artefact to the final target used after electrophysiological recording on the fused images was 0.48 mm, 0.69 mm, and 2.9 mm in the x, y, and z axes, respectively. No postoperative MRI related complication was observed. Conclusion: Both direct visualisation of the STN on MRI and intraoperative electrophysiological recording are important in defining the best target. Individual variations exist in the location of the STN target. Fewer tracks were required to define STN activity on the side operated first. Our current stereotactic method of electrode placement is relatively accurate.

Summary objective Pituitary tumour transforming gene (PTTG) encodes a multifunctional protein that is implicated in initiating and perpetuating pituitary adenoma growth. PTTG appears to have key regulatory functions in determining control of many fundamental cellular events including mitosis, cell transformation, DNA repair and gene regulation. Several of these events are mediated through interactions with PTTG binding factor (PBF) and fibroblast growth factor-2 (FGF-2). Given this background, we have determined the expression of PTTG, PBF, FGF-2 and its receptor FGF-R-1 in a large cohort of pituitary adenomas and have sought associations between levels of gene expression and clinical markers of tumour behaviour. patients and methods We used real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analyses to measure PTTG, PBF, FGF-2 and FGF-R-1 expression in ex vivo pituitary tumours (N = 121). Clinical data, including accurate radiological assessment of tumour characteristics, were used to determine any associations between gene expression and tumour behaviour. results PTTG was increased significantly (fivefold, P = 0·005) in adenomas compared with normal pituitaries. We also demonstrated that PBF was similarly raised in adenomas (sixfold, P = 0·0001), and was significantly correlated with PTTG expression. FGF-2 and its receptor FGF-R-1 were also raised in adenomas compared with normal pituitary tissue. Moreover, significantly enhanced expression of FGF-R-1 was observed in invasive adenomas compared with other pituitary tumours. conclusions Our data support a fundamental role for PTTG-mediated upregulation of FGF-2 signalling in pituitary tumorigenesis and growth, and suggest that receptor-mediated mechanisms of growth factor action may be critically important. Further prospective studies are required to determine whether measurement of FGF-R-1 mRNA will be of clinical use as a prognostic marker in patients with pituitary adenomas.

Sarcopenia and changes in body composition following neoadjuvant chemotherapy (NAC) may affect clinical outcome. We assessed the associations between CT body composition changes following NAC and outcomes in oesophageal cancer.A total of 35 patients who received NAC followed by oesophagectomy, and underwent CT assessment pre- and post-NAC were included. Fat mass (FM), fat-free mass (FFM), subcutaneous fat to muscle ratio (FMR) and visceral to subcutaneous adipose tissue ratio (VA/SA) were derived from CT. Changes in FM, FFM, FMR, VA/SA and sarcopenia were correlated to chemotherapy dose reductions, postoperative complications, length of hospital stay (LOS), circumferential resection margin (CRM), pathological chemotherapy response, disease-free survival (DFS) and overall survival (OS).Nine (26 %) patients were sarcopenic before NAC and this increased to 15 (43 %) after NAC. Average weight loss was 3.7 % ± 6.4 (SD) in comparison to FM index (-1.2 ± 4.2), FFM index (-4.6 ± 6.8), FMR (-1.2 ± 24.3) and VA/SA (-62.3 ± 12.7). Changes in FM index (p = 0.022), FMR (p = 0.028), VA/SA (p = 0.024) and weight (p = 0.007) were significant univariable factors for CRM status. There was no significant association between changes in body composition and survival.Loss of FM, differential loss of VA/SA and skeletal muscle were associated with risk of CRM positivity.• Changes in CT body composition occur after neoadjuvant chemotherapy in oesophageal cancer. • Sarcopenia was more prevalent after neoadjuvant chemotherapy. • Fat mass, fat-free mass and weight decreased after neoadjuvant chemotherapy. • Changes in body composition were associated with CRM positivity. • Changes in body composition did not affect perioperative complications and survival.

A case of intramedullary spinal metastasis presenting 14 months after excision of the primary anaplastic cerebral oligodendroglioma is presented. To the best of our knowledge, less than 10 cases of spinal metastasis have been reported in the world literature.

We report the potentials elicited by posterior tibial nerve stimulation and recorded simultaneously from the scalp and from electrodes within the interhemispheric fissure. The primary cortical potential was recorded from cortex contralateral but from scalp ipsilateral to the stimulated nerve. The scalp recordings thus demonstrated “paradoxical lateralization” as reported previously, and the similar morphology of the scalp and contralateral cortical recordings confirm that this “paradoxical lateralization” is most likely the result of a horizontal dipole located within the interhemispheric fissure.

Percutaneous glycerol rhizotomy (PGR) is an established technique to treat trigeminal neuralgia. Our aim was to establish how safe and efficacious repeat glycerol rhizotomies were on a study of 179 PGRs performed in our institution. There was an overall success rate of 92.1% in improvement of facial pain. Nine patients had reduced facial sensation post-operatively. There were no cases of anaesthesia dolorosa. The mean time to repeat injection was 22.9 months (1–108 months). Of those requiring repeat glycerol rhizotomies within 6 months, 23% had multiple sclerosis. There was no evidence that the number of repeat glycerol rhizotomies affects the probability of them having a complication (p = 0.87). Glycerol rhizotomy for trigeminal neuralgia is a safe and efficacious method of pain relief, which is particularly useful in the elderly. It can be repeated many times with no increase in morbidity and most importantly, in our practice, no anaesthesia dolorosa.

Deep brain stimulation (DBS) is an emerging therapeutic option for severe, treatment-resistant Tourette Syndrome (TS), with about 40 cases reported in the scientific literature over the last decade. Despite the production of clinical guidelines for this procedure from both European and USA centres, a number of unresolved issues still persist, mainly in relation to eligibility criteria and brain targets. The present article illustrates the UK perspective on DBS in TS and proposes consensus-based recommendations for double-blind controlled trials.

This report describes a case of prolactinoma that presented acutely with a third nerve palsy without evidence of apoplexy. The third nerve palsy resolved within 48 h on medical therapy. This is an atypical clinical presentation that highlights a successful and novel medical approach to treatment.

Analysis of amino acids derivatized by reaction with naphthalene-2,3-dicarboxaldehyde (NDA) was investigated using high-performance capillary electrophoresis (HPCE) combined with laser-induced fluoroescence detection. Of the HPCE modes, capillary zone electrophoresis, micellar electrokinetic chromatography and cyclodextrin (CD)-modified micellar electrokinetic chromatography (CD-MEKC) were applied to the separation of these amino acid derivatives. CD-MEKC allowed separation in less than 30 min and proved to be effective for chiral separation in some cases. A detection limit of 0.8 amol was obtained for NDA-labelled leucine at a signal-to-noise ratio of 2.

Preliminary experiments were performed to detect carbohydrates at various metal electrodes in anion-exchange chromatography (AEC). The metallic wire forms of copper, rhodium, cobalt, silver, iridium, palladium, iron, tantalum, zirconium, niobium, nickel and copper-nickel alloy were investigated as working electrodes. Some of these materials exhibited an electrocatalytic response for the oxidation of glucose with sodium hydroxide solution as a mobile phase in AEC. Copper electrodes produced the lowest detection limit for glucose among the materials examined. For the development of a highly sensitive detection method for carbohydrates, copper wire electrodes have been extensively investigated in AEC. A linear response for glucose was obtained ranging from 1 pmol to 1 nmol for the 10-μl sample volume employed. The detection limit was 110 fmol for glucose at a signal-to-noise ratio of 3. The experimental parameters which affected the response of carbohydrates were also examined.

Sleep disturbances in Parkinson’s disease (PD) are both widespread and wide-ranging. Emerging early in the disease process, sometimes prior to the onset of motor symptoms, sleep disruption results from the degeneration of the basal ganglia that is the hallmark of the disease, as well as changes in brain stem sleep centres. Accordingly, sleep problems consist of motor symptoms such as stiffness, difficulty turning and dystonia as well as disruption to the normal sleep–wake cycle, arousal and alertness. Sleep disruption has been associated with reduced quality of life (QOL) and increased depression and anxiety in PD patients and their caregivers alike, and may be severe enough to impair everyday functioning. It is also likely that presence of certain sleep symptoms such as REM behaviour disorder (RBD) and sleep-disordered breathing (SDB) are the harbingers of a poor prognosis. Although no studies have yet investigated the effect of sleep problems on institutionalization in PD, chronic disruption to the sleep of caregivers may well lead to a breakdown in the caregiving relationship and care arrangements. The following article reviews the prevalence, phenomenology, pathophysiology and impact of sleep disturbances on QOL for individuals with PD and their caregivers. Clinical management strategies are discussed.

An elecrochemical microband thin-layer flow cell that incorporates a thin glassy carbon electrode was fabricated and tested. The microband, tested with ferrocyanide and catecholamine oxidation, exhibited properties of a microelectrode with excellent electroactivity and signal-to-noise (S/N) response. For the chromatographic determination of several catecholamines at the 100 fmol level, the relative standard deviation as measured by the peak height ranged from 3–8%. The detection limit for DOPAC was 5 fmol (S/N = 3). The microband thin-layer cell gives an improved S/N ratio at an applied potential of 0.6 V vs. Ag/AgCl compared to that of a conventionally sized glassy carbon electrode. The small surface area of the microband allows rapid stabilization of chromatographic background (baseline) following the application of the potential. The microband thin-layer flow cell has a volume of 5 μL and exhibits a flow-rate-independent response, reduced ohmic drop, and gradient elution capability. The microband cell has great potential for commercialization as a universal detector for liquid chromatography.

Cholecystokinin (CCK) is a peptide found widely distributed throughout the gut and nervous systems. There is growing evidence that it affects growth and differentiation of several types of cell, including anterior pituitary cells, via two receptor subtypes, A and B. An autocrine/paracrine role for CCK in GH3 rat pituitary tumor cells has been reported. Herein, we demonstrate that functionless human pituitary tumors also possess CCK-B receptors. Total RNA was extracted from 30 human functionless pituitary tumors, reverse transcribed into cDNA, and subjected to PCR using primers specific for CCK-A and CCK-B receptors. The primers were targeted against different exons of the receptor genes, allowing identification of cDNA amplification. PCR bands of the predicted length were observed in all tumors using CCK-B receptor primers. Restriction digestion and direct sequence analysis of the products provided further evidence that they represented CCK-B receptor mRNA. CCK-A receptor mRNA was not detected by this RT-PCR analysis. In culture, CCK and CCK octapeptide sulphate powerfully stimulated phosphatidylinositol hydrolysis, providing evidence for functional activity of the CCK-B receptors. Similar analyses on pituitary-derived fibroblasts yielded negative results, indicating that the CCK-B receptor mRNA was expressed by tumors cells. These results suggest a role for CCK in the development of human functionless pituitary tumors.

✓ Pituitary carcinoma is rare, with fewer than 100 cases having been reported in the English-language literature. The diagnosis of pituitary carcinoma requires the demonstration of cerebrospinal and/or systemic metastases rather than local invasion. The lesion carries a poor prognosis; fewer than 50% of patients survive beyond 1 year after diagnosis. In this report the authors describe the case of a 68-year-old man who had undergone transsphenoidal debulking surgery and pituitary radiotherapy 4 years earlier for a pituitary adenoma. He presented with cervical cord compression due to a single metastasis from pituitary carcinoma. The authors discuss the management of this entity and review the literature for current opinion on the pathogenesis of these tumors, factors resulting in malignant transformation, and the reliability of markers that predict future malignant behavior. Evidence for the various treatment modalities is also appraised.

Background and objective The rarity of pituitary apoplexy renders it a difficult subject for audit; hence there are no evidence-based standards of optimum care for such patients. The key controversy in management relates to the role of acute neurosurgical intervention. In recent years we have adopted a relatively conservative approach towards patients presenting with pituitary apoplexy. Against this background, we aimed to determine whether our less-interventional approach affected long-term clinical outcome in these patients. Patients and design A retrospective analysis was performed to evaluate clinical presentation, management and clinical outcomes in a cohort of patients who presented acutely with pituitary apoplexy during the period 1994-2004. Data from 33 patients (13 female) were included, with a mean age of 52 (range 27-79) years and mean follow-up duration of 3.7 (0.4-10.1) years. Results The most common presenting symptoms were headache (97%), visual deficits (82%) and nausea/vomiting (78%). Fifteen patients (46%) underwent transsphenoidal surgery while 18 were managed conservatively. Indications for surgery were deteriorating visual deficit (n = 13), hemiparesis (n = 1) and altered conscious level (n = 1). Eight patients in the surgical group had ocular paresis that resolved in 63% following surgery, and seven had visual field defects with recovery in 57% postsurgery. Conservative management was reserved for patients with absent, or evidence of resolving, visual deficits at presentation. In this group, seven presented initially with ocular paresis and six with visual field defects but all made full recoveries. Of the patients managed neurosurgically, 87% required long-term glucocorticoid replacement and 60% required long-term thyroid hormone replacement. Conservatively managed patients required glucocorticoid replacement in 72% and thyroid hormone replacement in 72% of cases (P = NS between the two groups). Sex steroid replacement was required in 67% and 83% of patients managed neurosurgically and conservatively respectively (P = NS). At latest follow-up one patient in the conservatively managed group had required surgery and one in the surgically managed group had received pituitary radiotherapy, in both instances due to evidence of tumour regrowth on magnetic resonance imaging (MRI). Conclusion Our findings suggest that patients presenting with pituitary apoplexy in whom visual deficits are stable or improving may be managed expectantly as there is no identifiable deleterious effect on visual or endocrine outcome. One patient from each group experienced tumour regrowth that necessitated further treatment intervention, highlighting the importance of long-term follow-up in patients with pituitary apoplexy.

Two forms of the growth hormone-releasing hormone (GHRH) receptor (GHRH-R) exist in terms of a polymorphism at codon 57. The most common allele possesses GCG, coding for Ala. This codon can also be ACG, replacing the Ala with Thr. The present study demonstrates that the latter occurs in about 20% of pituitary somatotrophinomas, removed from patients with acromegaly. Somatotrophinomas possessing the alternative allele respond, on average, more strongly to GHRH in terms of GH secretion in vitro than tumors which are homozygous for the more common allele. The distribution of the two allelic forms of the GHRH-R did not significantly differ between acromegalic and non-acromegalic subjects. Thus, while the alternative allelic forms may, at least partially, contribute to the variable response of serum GH levels to i.v. GHRH observed in acromegalic and normal subjects, it is unlikely that subjects possessing the rarer form containing Thr in place of Ala at residue 57 are at increased risk of developing acromegaly.

Malignant fibrous histiocytoma is uncommon within the central nervous system. It is a pleomorphic sarcoma originally found in soft tissue(1) and there are few reported cases within the central nervous system, in particular the cerebellum. This tumour is difficult to diagnose and may be difficult to treat. We present a case of cerebellar malignant fibrous histiocytoma, its management and literature review.

L-dopa given to Parkinson9s disease (PD) patients for prolonged periods or at sustained high doses is known to produce disabling choreiform and dystonic dyskinesias. The production of dystonic dyskinesias at small doses in patients with deep brain stimulation surgery (DBS) has been poorly reported. We present a case series of 13 patients who tolerated high doses of l-dopa prior to DBS, who subsequently developed severe disabling dystonic dyskinesias on minimal doses of l-dopa after surgery. Of the 13 patients (7 male, 6 female), mean age was 54 (range 46–63), and mean disease duration was 10 years (range 6–17). 11 patients had presented with tremor as their first motor symptom of PD, and 10 had developed dyskinesias prior to surgery. At time of DBS the mean calculated L-dopa equivalent dose was 1073 mg (range 480–1566.7 mg) of which the mean l-dopa dose was 581 mg (range 300–1350 mg). The mean time from DBS to develop dystonic dyskinesias was 3 years (range 0.3–5 years), at which time the mean l-dopa equivalent dose was 366 mg (range 50–660 mg) and the mean l-dopa dose was 196 mg (range 50–600). Replacing l-dopa with a dopamine agonist either removed or largely relieved this motor complication. This case series highlights an important motor complication in the DBS PD patient and suggests one method to ameliorate it. It also raises important questions about the mechanism for reduction of dyskinesia threshold following DBS.

Subthalamic deep brain stimulation (STN DBS) for Parkinson9s disease typically enables a 50% reduction in dopaminergic medication postoperatively. This reduction in medication is accompanied by a 60% reduction in dyskinesia and a reduction in off periods. However, there remains a subgroup of patients who have disabling dyskinesias despite optimisation of drug and stimulator setting. Amantadine is sometimes used for the medical management of drug-induced dyskinesias in Parkinson9s disease. Its use in dyskinesias after DBS has not been formally assessed. We report a series of 8 cases who had bilateral STN DBS. These patients had similar characteristics to our local database of patients who have had DBS. However, these patients had disabling bradykinesia and/or dyskinesias despite attempts at optimisation of stimulator settings and dopaminergic medication. The addition of amantadine led to clear improvements in dsykinesias and/or mobility, without the need to increase the total dose of dopaminergic medication. Stopping amantadine caused worsening of symptoms. This case series suggests amantadine is an important additional medication in the small group of patients whose disease has not been stabilised after DBS. The outflow of the STN includes a glutamatergic pathway. The glutamate receptor blocking properties of amantadine provide a possible mechanism for the observed benefit. We plan to extend the results of this case series to include objective scoring in subsequent patients.

Background A number of epidemiologic studies show a decreased risk of non-melanoma cancer in Parkinson9s disease (PD). Cigarette smoking is less prevalent in PD and hence the risk of smoking related neoplasia such as lung and colon would be expected to be decreased in PD. A link is shown between decreased physical activity and colorectal cancer. Increased dietary intake of iron increases colorectal cancer risk and iron deposition in the basal ganglia is a feature of PD. Thus common mechanisms may be involved in both disorders. Our study looks at a cohort of surgically treated PD patients to see if there is an altered risk of colorectal cancer among them. Method In our population of patients fitted with a deep brain stimulator between 2002 and 2010, we searched for causes of death confirmed against death certificates and a histological diagnosis of colorectal cancer in the patient records. Results Of 22 patients who had died, 3 had a diagnosis colorectal cancer. 1 more died of a carcinoembryonic antigen positive cancer of unknown origin. Discussion From UK national statistics, colorectal cancer accounts for between 2.7 and 3.2% of all deaths. Although the small number of deaths in our cohort requires careful interpretation of the results, 14% of our cohort having a diagnosis of colorectal cancer suggests that the lifetime risk of colorectal cancer is not reduced in PD patients. This observation merits further investigation in a larger cohort of PD patients.

Background Deep Brain Stimulation (DBS) is used for people with Parkinson’s disease (PwPD) who are experiencing motor complications that are not controlled by medication. To date, PD SURG is the largest trial to compare DBS to best medical therapy in PwPD. Outcomes to DBS for PwPD are varied and there is an ongoing question as whether patient selection can be improved. To date, subgroup analyses have not been powered to provide an answer. An algorithm (STIMULUS) was designed to try to identify suitable candidates for DBS for PD symptoms based on the clinical opinion of an expert panel. The PD SURG data set provides an opportunity to test the ability of STIMULUS to predict suitable candidates.