Localized myxedema histologically mimicking spindle cell lipoma.

In this report, a 55-year-old woman with Graves disease and exophthalmos had a recurrent nodule on the foot. Her initial biopsy and excision specimens were believed to be consistent with spindle cell lipoma, which aligned with her early tumor-like clinical morphology. Her tumor recurred after excision, which is not consistent with spindle cell lipoma. As her condition progressed, her clinical morphology became more consistent with localized myxedema and her biopsies were congruent, securing clinicopathologic correlation. With standard treatment for localized myxedema, she improved significantly. This case emphasizes how clinicians need to have high suspicion for localized myxedema in patients with history of Graves disease and exophthalmos. It also emphasizes how localized myxedema should be included in the histologic differential diagnosis for spindle cell lipoma with prominent myxoid stroma, particularly in those not responding to treatment as anticipated.

Evaluating the perioperative safety of laparoscopic radical nephrectomy for large, non-metastatic renal tumours: a comparative analysis of T1-T2 with T3a tumours.

OBJECTIVE: With increasing surgeon experience, the use of laparoscopic radical nephrectomy (LRN) in large and locally advanced renal tumours (T3a) is gaining favour in urological practice. There are limited studies reporting surgical outcomes in such groups. The aim of this study was to review our experience with LRN in these patients. METHODS: Data was retrospectively collected on 201 consecutive patients who underwent LRN for renal cancer by a single surgeon. Perioperative parameters assessed were age, gender, American Society of Anaesthesiologists score (ASA), waist circumference, tumour size, specimen size, histological subtypes, anaesthetic duration, operative approach and technique, surgery duration, blood loss, pre and postoperative renal function, complication rate and duration of hospital stay. RESULTS: Of 201 patients undergoing LRN, 43 (21%) patients had T3a tumours (group 2). The remaining 158 (79%) patients had T1 tumours (group1). Mean tumour size in group 2 was 12.2 cm. Renal cell carcinoma (RCC) was more common in males than females (131/201; 65%). Patients with T3a disease were more likely to have an ASA score of 2 (37/201; 18%). In the majority of patients across both groups, LRN was completed using a 3-port approach (173/201; 86%). There were no significant differences between groups in terms of mean anaesthetic duration, average surgical time, average estimated blood loss, complication rate and mean hospital stay. CONCLUSION: Our study shows that LRN has equivalent perioperative outcomes and safety in larger and locally advanced renal tumours.

The Effect of Obesity and Increased Waist Circumference on the Outcome of Laparoscopic Nephrectomy.

Introduction. The prevalence of obesity is increasing worldwide. Obesity can be determined by body mass index (BMI); however waist circumference (WC) is a better measure of central obesity. This study evaluates the outcome of laparoscopic nephrectomy on patients with an abnormal WC. Methods. A WC of >88 cm for women and >102 cm for men was defined as obese. Data collected included age, gender, American Society of Anaesthesiologists (ASA) score, renal function, anaesthetic duration, surgery duration, blood loss, complications, and duration of hospital stay. Results. 144 patients were assessed; 73 (50.7%) of the patients had abnormal WC for their gender. There was no difference between the groups for conversion to open surgery, number of ports used, blood loss, and complications. Abnormal WC was associated with a longer median anaesthetic duration, 233 min, IQR (215-265) versus 204 min, IQR (190-210), p = 0.0022, and operative duration, 178 min, IQR (160-190) versus 137 min, IQR (128-162), p < 0.0001. Patients with an abnormal WC also had a longer inpatient stay, p = 0.0436. Conclusion. Laparoscopic nephrectomy is safe in obese patients. However, obese patients should be informed that their obesity prolongs the anaesthetic duration and duration of the surgery and is associated with a prolonged recovery.

A single centre experience of zero-ischaemia laparoscopic partial nephrectomy in Ireland.

BACKGROUND: Nephron-sparing surgery in the form of partial nephrectomy is increasingly becoming the standard of care in patients with small renal tumours. Oncological outcomes for partial nephrectomy are equivalent to radical nephrectomy, however, clamping of the hilar vessels to allow resection of tumours during partial nephrectomy may cause ischaemic damage to the kidney and result in long-term renal impairment. AIM: We carried out a retrospective review of 43 patients undergoing laparoscopic partial nephrectomy (LPN) and assessed functional and oncological outcomes. METHODS: The operative technique initially utilised a thulium laser, with later cases using the LigaSure™ vessel sealing device. All patients underwent preoperative cross sectional imaging and anatomical classification accordingly. RESULTS: Forty three patients underwent LPN in our unit from 2006 to 2014. The mean (range) tumour diameter on preoperative cross sectional imaging was 28.2 (12-49) mm. All cases had a warm ischaemia time of zero, as hilar vessels were not clamped in any case. The mean (range) preoperative estimated glomerular filtration rate (eGFR) was 73 (37 to >90) ml/min/1.73 m2 and was not significantly different to the post-operative mean (range) eGFR of 71 (31 to >90) ml/min/1.73 m2. 34 (79%) of the tumours were found to be malignant. Positive surgical margins were found in one case. The mean (range) follow-up time in our cohort was 61.6 (24-127) months and no patient has had a local or distant recurrence. CONCLUSION: Zero ischaemia laparoscopic partial nephrectomy appears to be a safe and oncologically satisfactory procedure for the management of small localised kidney tumours.

Alloantibody Responses After Renal Transplant Failure Can Be Better Predicted by Donor-Recipient HLA Amino Acid Sequence and Physicochemical Disparities Than Conventional HLA Matching.

We have assessed whether HLA immunogenicity as defined by differences in donor-recipient HLA amino-acid sequence (amino-acid mismatch score, AMS; and eplet mismatch score, EpMS) and physicochemical properties (electrostatic mismatch score, EMS) enables prediction of allosensitization to HLA, and also prediction of the risk of an individual donor-recipient HLA mismatch to induce donor-specific antibody (DSA). HLA antibody screening was undertaken using single-antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The effect of AMS, EpMS, and EMS on the development of allosensitization (calculated reaction frequency [cRF]) and DSA was determined. Multivariate analyses, adjusting for time on the waiting list, maintenance on immunosuppression after transplant failure, and graft nephrectomy, showed that AMS (odds ratio [OR]: 1.44 per 10 units, 95% CI: 1.02-2.10, p = 0.04) and EMS (OR: 1.27 per 10 units, 95% CI: 1.02-1.62, p = 0.04) were independently associated with the risk of developing sensitization to HLA (cRF > 15%). AMS, EpMS, and EMS were independently associated with the development of HLA-DR and HLA-DQ DSA, but only EMS correlated with the risk of HLA-A and -B DSA development. Differences in donor-recipient HLA amino-acid sequence and physicochemical properties enable better assessment of the risk of HLA-specific sensitization than conventional HLA matching.

Believe it or not: Moving non-biological stimuli believed to have human origin can be represented as human movement.

Does our brain treat non-biological movements (e.g. moving abstract shapes or robots) in the same way as human movements? The current work tested whether the movement of a non-biological rectangular object, believed to be based on a human action is represented within the observer's motor system. A novel visuomotor priming task was designed to pit true imitative compatibility, due to human action representation against more general stimulus response compatibility that has confounded previous belief experiments. Stimulus response compatibility effects were found for the object. However, imitative compatibility was found when participants repeated the object task with the belief that the object was based on a human finger movement, and when they performed the task viewing a real human hand. These results provide the first demonstration that non-biological stimuli can be represented as a human movement if they are believed to have human agency and have implications for interactions with technology and robots.

Use of Ex Vivo Normothermic Perfusion for Quality Assessment of Discarded Human Donor Pancreases.

A significant number of pancreases procured for transplantation are deemed unsuitable due to concerns about graft quality and the associated risk of complications. However, this decision is subjective and some declined grafts may be suitable for transplantation. Ex vivo normothermic perfusion (EVNP) prior to transplantation may allow a more objective assessment of graft quality and reduce discard rates. We report ex vivo normothermic perfusion of human pancreases procured but declined for transplantation, with ABO-compatible warm oxygenated packed red blood cells for 1-2 h. Five declined human pancreases were assessed using this technique after a median cold ischemia time of 13 h 19 min. One pancreas, with cold ischemia over 30 h, did not appear viable and was excluded. In the remaining pancreases, blood flow and pH were maintained throughout perfusion. Insulin secretion was observed in all four pancreases, but was lowest in an older donation after cardiac death pancreas. Amylase levels were highest in a gland with significant fat infiltration. This is the first study to assess the perfusion, injury, as measured by amylase, and exocrine function of human pancreases using EVNP and demonstrates the feasibility of the approach, although further refinements are required.

The effect of a Rapid Access Prostate Cancer Clinic on prostate cancer patient and disease characteristics, primary treatment and surgical workload.

BACKGROUND: In 2009, Rapid Access Prostate Cancer Clinics (RAPC) were introduced to St. James's Hospital to improve the access and organisation of patients to prostate cancer investigations and treatment. AIMS: To observe the effects of the RAPC on prostate cancer diagnosis, primary treatment and overall workload. METHODS: Using a prospectively designed patient database, the records of all prostate cancer patients between 2007 and 2011 were retrieved and analysed. Data were obtained for age, PSA, biopsy Gleason score and primary treatment modality and charted for the observation and comparison of trends. RESULTS: Seven hundred and eighty-nine patients had a new diagnosis of prostate cancer between 2007 and 2011. The median PSA prior to the RAPC was 9.7-13.1 ng/ml, which decreased to 7.79-9 ng/ml after the RAPC. Prior to the RAPC, 77-81 biopsies were performed annually versus 149-271 in the post-RAPC era. Annual requirements for radical prostatectomy also increased from 12 to 27 in the post-RAPC era. Conversely, an initially increasing percentage of patients for radiotherapy was reversed in the post-RAPC period. An increasing trend for higher grade PCa (Gleason score 4 + 4 and higher) was also reversed. CONCLUSIONS: The introduction of a RAPC improves the overall pathological characteristics of patients with prostate cancer. However, RAPCs are also associated with a considerable increase in surgical workload. These are important considerations for units considering the incorporation of a similar facility in their institutions.

Audit of rapid access introduction reveals high prevalence of prostate cancer in Western Region.

INTRODUCTION: Men with symptoms suggestive of prostate cancer are now directly referred by their general practitioners to rapid access prostate assessment clinics (RAPACs). This service implements recommendations outlined by the National Cancer Control Programme. The RAPAC was introduced at Galway University Hospital, Galway, Ireland in June 2009, aiming to structure GP referral of patients with suspected prostate cancer to a urology service. AIMS: The aims of this study are to assess our initial experience with particular emphasis on access times, patient demographics, detection rates and treatment outcomes. METHODS: Data on all patients presenting to the RAPAC during the preliminary 2-year period have been gathered prospectively and analysed using standard parametric analysis methods. RESULTS: A total of 1,106 patients were reviewed at 278 clinic sessions during the initial 2-year period. The average waiting time to first clinic visit was 18 days (12-39 days). The mean age of referral to the clinic is 65 years (44-88 years). The mean PSA is 16.31 g/dL (0.4-845 g/dL). Of the 1106 patients undergoing TRUS biopsies, 503 (45.5 %) patients were diagnosed with prostate cancer. Further analysis patient demographics and cancer grading is presented in the article. Seventy-one patients (14.1 %) underwent radical retropubic prostatectomy. Sixty-seven patients (13.3 %) are being followed on an active monitoring programme, whilst 235 (56.7 %) received primary treatment with external beam radiotherapy and 68 (13.5 %) received brachytherapy. CONCLUSION: This data highlight the necessity of a RAPAC to streamline the provision of prostate cancer services in the west of Ireland.

Spatio-temporal epidemiology of Campylobacter jejuni enteritis, in an area of Northwest England, 2000-2002.

A total of 969 isolates of Campylobacter jejuni originating in the Preston, Lancashire postcode district over a 3-year period were characterized using multi-locus sequence typing. Recently developed statistical methods and a genetic model were used to investigate temporal, spatial, spatio-temporal and genetic variation in human C. jejuni infections. The analysis of the data showed statistically significant seasonal variation, spatial clustering, small-scale spatio-temporal clustering and spatio-temporal interaction in the overall pattern of incidence, and spatial segregation in cases classified according to their most likely species-of-origin.

Rapid identification of uropathogenic Escherichia coli of the O25:H4-ST131 clonal lineage using the DiversiLab repetitive sequence-based PCR system.

Several recent studies have highlighted the emergence of a globally disseminated clone of uropathogenic and invasive Escherichia coli isolates of serotype O25:H4 and sequence type 131. The ability to characterize rapidly E. coli isolates of this lineage would facilitate enhanced surveillance for this pathogen. We have used the semi-automated DiversiLab repetitive PCR-based system to analyse a collection of 35 clinical isolates of uropathogenic E. coli from across the UK, with particular focus on the O25:H4-ST131 lineage. All isolates had been characterized using multilocus sequence typing (MLST), and 14 had previously been typed using pulsed-field gel electrophoresis (PFGE). The DiversiLab system allowed discrimination of O25:H4-ST131 isolates from those of other E. coli lineages. It was slightly more discriminatory than MLST, but was less discriminatory than PFGE. With an analysis time of <4 h between receipt of a cultured organism and provision of a typing result, the system offers information on a real-time basis, a major advantage over current practice. We suggest that introduction of the DiversiLab system would be useful for rapid exclusion of E. coli isolates during outbreak investigations, and that the approach could be employed for surveillance for pathogenic or antibiotic-resistant clones of this organism.

Chemical signal mediated premating reproductive isolation in a marine polychaete, Neanthes acuminata (arenaceodentata).

Neanthes acuminata Ehlers (1868) is a monogamous coastal polychaete with male parental care and a high level of sexual selection. We measured the level of prezygotic isolation among allopatric populations of N. acuminata; from the East and West Coast of the USA, a population from Hawaii, and a laboratory culture originating from Los Angeles, CA. All populations were found to preferably mate with members of their own population. Individuals from populations from Atlantic vs. Pacific Ocean failed to pair and to mate, either during the 10 min or 48 hr experiments. Instead, individuals showed high levels of aggressive behavior. Experiments measuring the levels of interpopulation aggression, established that individuals can recognize and discriminate among different populations of N. acuminata on the basis of olfactory cues. Aggressive behavior was induced by exposure of animals to seawater "conditioned" by individuals from the other populations, thus demonstrating the role of olfaction in the detection of "home" populations. The aggressive display was stronger upon exposure to seawater conditioned with "unrelated" populations and especially between Pacific and Atlantic populations.

Lentivirus-mediated gene transfer of viral interleukin-10 delays but does not prevent cardiac allograft rejection.

Human immunodeficiency virus (HIV)-based lentiviral vectors expressing viral interleukin-10 (vIL-10) were used to transduce rat cardiac allografts with the aim of extending graft survival. vIL-10 expression was first shown, by RT-PCR, to persist in transduced heart isografts for at least 28 days after transduction. Cardiac transplants were performed in a fully allogeneic rat strain combination (Lewis to DA); allografts transduced by vectors expressing vIL-10 showed significantly prolonged survival (14.5 vs 7.5 days median survival time). Mixed lymphocyte reactions (MLRs) were used to determine the influence, in vitro, of vIL-10 on alloantigen-induced T-cell proliferation. Bioactive vIL-10, produced by DA rat aortic endothelial cells transduced with HIV-PGK-vIL-10, was added to MLRs at different time points and lymphocyte proliferation was assessed by uptake of [3H]thymidine. T-cell proliferation was inhibited by >80% when vIL-10 was added to the MLR at day 1, 2 or 3 of coculture. The inhibitory effect was significantly decreased when addition of vIL-10 was delayed until day 4 or 5 (47 and 35% inhibition, respectively). The extended graft survival time is comparable to that using adenoviral vectors delivering vIL-10 in a similar rat strain combination. The limited improvement in survival may be due to lack of inhibition of the early phase of the alloimmune response as suggested by in vitro studies confirming that maximum suppression of the MLR by vIL-10 can only be achieved if the cytokine is present at the initiation of alloimmune recognition. The delay in expression of vIL-10 from the lentiviral vector means that protocols must be developed to suppress the early stages of alloimmune stimulation before vIL-10 is produced.

A new source of hepatocytes for transplantation.

INTRODUCTION: The most effective treatment for acute or chronic liver failure is orthotopic liver transplantation. Worldwide there is a shortage of organs for transplantation. This shortage has called for research into new treatments for management of patients with liver failure. One such treatment is hepatocyte transplantation. During liver resections considerable amounts of normal liver are unavoidably resected. We aim to harvest these hepatocytes and to filter the tumor cells from them to provide a source for transplantation. MATERIALS AND METHODS: After liver resection, the largest vessel at the resected liver edge was identified and cannulated. Seglen's two-stage technique of perfusing the liver with EDTA and collagenase was performed to harvest the hepatocytes. Ep-CAM Ags are consistently present on the surface of epithelial cells and in particular in colorectal cancer cells. Therefore, MOC31 antibodies (selective Abs for Ep-CAM) attached to magnetic beads were used to target the tumor cells. These tumor cells are selectively removed using a magnet. CEA staining was then used to ensure the hepatocyte collection was tumor cell free. Five million hepatocytes were rosetted with one million HT29 CRC cells to assess the immunomagnetic filtration technique. RESULTS: The hepatocyte harvesting resulted in 864,000 viable hepatocytes to be harvested per gram of liver. Histochemical staining using CEA demonstrated 75% of the HT29 cells in the hepatocyte collection were removed after one use of magnetic beads. CONCLUSION: We have demonstrated the successful initial stages of harvesting tumor-free hepatocytes from liver resected for malignancy.

Health problems following Campylobacter jejuni enteritis in a Lancashire population.

OBJECTIVES: Campylobacter jejuni enteritis can lead to musculoskeletal, neuropathic or other health sequelae. We investigated the coexistence, seasonal occurrence, strain-type associations and impact on work capacity of different health problems following C. jejuni enteritis in a Lancashire population during 1999 and 2001. METHODS: A semistructured questionnaire was used to characterize health problems that occurred in the community after laboratory-confirmed episodes of C. jejuni enteritis. The questionnaire was posted to all adults in the Preston and Chorley area who developed C. jejuni enteritis in 1999 or 2001. All Campylobacter isolates from this population were serotyped. RESULTS: Several types of sequelae occurred consistently in both years, including the coexistence of musculoskeletal and neuropathic problems. There was no evidence of C. jejuni strain-type associations or seasonal preponderance for any type of sequela. The overall health impact of C. jejuni enteritis, as measured by workdays lost, was high in this population. CONCLUSIONS: A variety of health problems occur consistently following C. jejuni enteritis and substantially increase morbidity due to campylobacteriosis in the community.