Evaluation of the Impact of Magnetic Resonance Imaging with Susceptibility-weighted Imaging for Screening and Surveillance of Radiation-induced Cavernomas in Long-term Survivors of Malignancy.

AIMS: Radiation-induced cavernomas (RIC) are common late toxicities in long-term survivors of malignancy following cerebral irradiation. However, the natural history of RIC is poorly described. We report the first series of long-term surveillance of RIC using modern magnetic resonance imaging (MRI) including highly sensitive susceptibility-weighted imaging (SWI). The aims of this research were to better characterise the natural history of RIC and investigate the utility of MRI-SWI for screening and surveillance. MATERIALS AND METHODS: Eligibility required long-term survivors of malignancy with previous exposure to cerebral irradiation and RIC identified on MRI-SWI surveillance. The number and size of RIC were reported on Baseline MRI-SWI and last Follow-up MRI-SWI. RESULTS: In total, 113 long-term survivors with RIC underwent MRI-SWI surveillance; 109 (96%) were asymptomatic at the time of RIC diagnosis. The median age at cerebral irradiation was 9.3 years; the median radiotherapy dose was 50.4 Gy. The median time from cerebral irradiation to Baseline MRI-SWI was 17.9 years. On Baseline MRI-SWI, RIC multiplicity was present in 89% of patients; 34% had >10 RIC; 65% had RIC ≥4 mm. The median follow-up from Baseline MRI-SWI was 7.3 years. On Follow-up MRI-SWI, 96% of patients had multiple RIC; 62% had >10 RIC; 72% had RIC ≥4 mm. Of the 109 asymptomatic patients at RIC diagnosis, 96% remained free from RIC-related symptoms at 10 years. Only two required neurosurgical intervention for RIC; there was no RIC-related mortality. CONCLUSIONS: RIC are commonly multiple, asymptomatic and typically increase in size and number over time. Our findings suggest that MRI-SWI for screening of RIC is unlikely to influence longer term intervention in asymptomatic cancer survivors. In the absence of neurological symptoms, assessment or monitoring of RIC are insufficient indications for MRI-SWI surveillance for long-term survivors of malignancy with past exposure to cerebral irradiation.

Management of inflammatory neurologic and psychiatric manifestations of systemic lupus erythematosus: A systematic review.

BACKGROUND: The neurological and psychiatric manifestations of systemic lupus erythematosus (NPSLE) are a heterogeneous group of conditions with variable clinical presentation and significant morbidity and mortality. OBJECTIVES: Our aim was to comprehensively assess and present the evidence for treatments used in the management of inflammatory NPSLE. METHODS: Medline, Embase, CINHAL and Cochrane CENTRAL were searched from 1990 to end of March 2019 using key words that related to NPSLE and treatment. Included studies comprised clinical trials, observational studies or case series with ≥5 patients and sufficient data related to treatment and outcome in NPSLE patients. RESULTS: There were 7222 studies identified in the search, of which 90 were included in the review. There was a notable paucity of clinical trials, with only two randomised controlled trials and one pilot study. Treatment categories included corticosteroids (14 studies), cyclophosphamide (18 studies), synthetic DMARDs (7 studies), biologic therapies (14 studies), therapeutic plasma exchange (6 studies), intravenous immunoglobulin (2 studies), autologous stem cell transplant (3 studies), other therapies (8 studies), combination therapies (6 studies), studies with grouped outcome data (5 studies) and observational studies with therapy-specific associations (7 studies). Corticosteroids are accepted as first line treatment in NPSLE and there is low-moderate evidence supporting their benefit. Moderate evidence, based on consistent data in numerous studies and some trial data, supports the use of cyclophosphamide in the treatment of NPSLE. Limited data support some synthetic DMARDs such as mycophenolate, azathioprine and intrathecal methotrexate. In refractory disease, low-moderate evidence supports rituximab therapy and limited evidence supports benefit following autologous stem cell transplant. Regarding adjuvant treatments, limited evidence favours addition of plasma exchange, intravenous immunoglobulin and hydroxychloroquine. There exists very limited data for other therapies. CONCLUSION: There are multiple therapeutic options for the management of inflammatory NPSLE including systemic, biologic and interventional therapies; however, currently there is a paucity of high-quality trial data to guide firm recommendations. In order to better understand the optimal treatment of NPSLE and its different subtypes, further well-designed clinical trials are needed.

Management of cutaneous manifestations of lupus erythematosus: A systematic review.

BACKGROUND: Cutaneous lupus erythematosus (CLE), occurring with or without systemic lupus erythematosus (SLE), is a group of inflammatory skin diseases that can be very debilitating, causing significant psychological distress, and sometimes scarring. OBJECTIVES: We sought to comprehensively present the evidence for different treatment modalities in patients with cutaneous manifestations of lupus erythematosus (LE). METHODS: Medline, Embase, Scopus and Cochrane CENTRAL were searched electronically from 1990 to March 2019, using keywords related to cutaneous lupus and synonyms and treatment. Articles retrieved were screened for relevance, including reference lists of retrieved reviews. We included clinical trials, observational studies or case series with ≥5 patients focussing on treatment of CLE, with or without SLE. RESULTS: The search identified 6637 studies, of which 107 were included. Each study commonly included a heterogeneous mixture of CLE subtypes, with or without SLE. The 107 included studies investigated 11 different categories of treatment in 7343 patients. Treatments included topical calcineurin inhibitors (13 studies), sun protection (5 studies), R-salbutamol cream (2 studies), antimalarials (22 studies), synthetic DMARDs (10 studies), retinoids (2 studies), thalidomide/lenalidomide (22 studies), biologic therapies (15 studies), intravenous immune globulin (3 studies), laser (6 studies) and other therapies (7 studies). General measures to be considered include smoking cessation, sun protection measures and optimisation of vitamin D levels. Moderate evidence exists for benefit with topical CNIs, particularly as a steroid sparing agent in areas at high risk of steroid complications (e.g. facial skin). There is moderate evidence for hydroxychloroquine, which is first-line in SLE patients, limited evidence to support other synthetic DMARDs, and moderate evidence supporting thalidomide but with significant risk of toxicity. Of biologic therapies, there are moderate data to support belimumab. Limited evidence exists for other therapies. CONCLUSION: Many management options are available for CLE, including topical, systemic and biologic therapies, with a variable balance of efficacy and toxicity. There is a paucity of high-quality clinical trial data. Further trials are required to better understand optimal management of CLE, particularly in specific subgroups.

First reported finding of a Malignant Pleural Mesothelioma in a patient post Liver Transplant.

The case history of a liver transplant recipient is presented, who presented with acute dyspnoea after an innocuous fall. His early management was complicated and he was eventually diagnosed with malignant mesothelioma. This is the first such case report in the literature.

The accuracy of magnetic resonance imaging in prostate cancer staging: a single-institution experience.

BACKGROUND: Magnetic resonance imaging (MRI) has a wide reported variation in sensitivity and specificity for staging prostate cancer (PCA). AIMS: We examined the accuracy of MRI in detecting PCA, and in identifying extracapsular extension (ECE) and seminal vesicle invasion (SVI) in PCA patients at our institution. METHODS: We retrospectively reviewed pre-biopsy MRI findings and correlated the same with subsequent radical prostatectomy pathology reports in all patients undergoing radical prostatectomy between 2010 and 2012. Specifically, comparison was made between MRI and pathologic stage. Age, serum prostate-specific antigen level and Gleason score were recorded. RESULTS: MRI detected signal abnormalities in 50 out of 88 PCA patients undergoing radical prostatectomy. Of these, 12 had ECE and 7 had SVI on final histology. The sensitivity and specificity of MRI for detecting ECE were 75 and 100%, respectively. The sensitivity and specificity of MRI for detecting SVI were 16.7 and 100%, respectively. The positive predictive values for determining ECE and SVI were 100% and negative predictive values were 96.2 and 90.6%, respectively. CONCLUSIONS: MRI may be reliable for excluding ECE and SVI in PCA patients where the lesion is visible on MRI. It has a good diagnostic ability for ECE, but is less accurate for identifying SVI. This article supports the use of MRI in the preoperative evaluation of PCA.

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.

Primary angiitis of the central nervous system: experience of a Victorian tertiary-referral hospital.

BACKGROUND: Primary angiitis of the central nervous system is a rare condition, which is often difficult to diagnose and is associated with significant morbidity and mortality. There is no standardised treatment protocol or randomised clinical trial evidence to guide management. AIM: To describe the clinical features, diagnostic modalities, treatment and outcomes in an Australian hospital population-based series of primary cerebral angiitis. METHODS: Data were collected via retrospective medical record review of patients with primary angiitis of the central nervous system for the period 1 July 1998 to 30 June 2009, using previously published diagnostic criteria. Eligible patient records were identified in two ways; from routinely collected hospital episode data, coded using the ICD-10-AM coding standard and by review of cerebral biopsy data. RESULTS: Ten of 12 included patients had a positive cerebral biopsy, with two patients diagnosed by angiography. Mean age at diagnosis was 47.2 years (range 18-73 years), with a female predominance of 5:1. Headache was the most common symptom experienced. Seventy per cent of the biopsy specimens showed a lymphocytic vasculitis. All patients received treatment with either steroids alone or a combination of steroids and cyclophosphamide, the latter treatment being initiated for those with a higher modified Rankin score of disability. Nine (75%) responded to treatment. There was one in-hospital death, and two patients had no documented response to treatment. CONCLUSION: This study presents the first Australian case series data of primary cerebral angiitis. Better understanding of management and outcomes of this rare condition would be gained through multicentre studies.

Plastic wound retractors as bacteriological barriers in gastrointestinal surgery: a prospective multi-institutional trial.

BACKGROUND: Surgical site infection remains a significant problem, and peri-operative strategies to reduce wound exposure to bacteria are needed urgently. Plastic ring wound retractors, used to gain access to the abdominal cavity, may shield the incision site from bacteria. AIM: To evaluate exposure of the surgical incision site to bacteria using a plastic ring wound retractor in gastrointestinal surgery. METHODS: Prospective, observational, multi-centre study. Patients undergoing clean-contaminated gastrointestinal surgery with standard antibiotic prophylaxis were included (N = 250 patients, 500 samples). A plastic wound retractor was used to facilitate access to the abdominal cavity. Samples were taken for bacterial culture from the inside (luminal) and outside (wound) surfaces of the retractor at the end of the operation. FINDINGS: Bacteria were found on 56% (140/250) of samples from the inside surface of the retractor compared with 34% (85/250) of samples from the outside surface of the retractor (P < 0.0001). There was no significant difference in skin-derived organisms from the inside [34/245 (14%)] and outside [27/250 (11%)] surfaces of the retractor (P = 0.108). However, enteric organisms were cultured twice as often from the inside surface of the retractor compared with the outside surface of the retractor (49% vs 26%, respectively; P < 0.0001). CONCLUSION: Plastic wound retractors reduce wound exposure to enteric bacteria in gastrointestinal surgery.

Radical prostatectomy outcome when performed with PSA above 20 ng/ml.

Many centres currently do not offer radical prostatectomy (RP) to men with high-risk localised prostate cancer due to concerns regarding poor outcome, despite evidence to the contrary. We identified 18 men undergoing RP with serum PSA >20 ng/ml (high-risk by National Comprehensive Cancer Network definition) and minimum follow-up of 12 years (mean 13.5). Mean preoperative PSA was 37.0 ng/ml (Range 21.1-94.0). Prostatectomy pathology reported extracapsular disease in 16 (88.9%), positive surgical margins in 15 (83%) and positive pelvic lymph nodes in 5 (27.8%). Overall and cancer-specific survival at 5 and 10-years was 83.3%, 88.2%, 72% and 76.5% respectively. With complete follow-up 11 (61.1%) are alive, and 5 (27.8%) avoided any adjuvant therapy. Complete continence (defined as no involuntary urine leakage and no use of pads) was achieved in 60%, with partial continence in the remainder. We conclude that surgery for this aggressive variant of localised prostate cancer can result in satisfactory outcome.

Pap smears for men: a vision of the future?

BACKGROUND: Anal intraepithelial neoplasia (AIN) rarely receives as much publicity as its neighbouring orifice, the cervix. As in the cervix, intraepithelial neoplasias are precursors to cancer in the anal canal. AIN and cervical interstitial neoplasia (CIN) undergo dysplasia as a consequence of human papillomavirus (HPV) infection. Since the advent of screening with the Pap smear in CIN, cervical cancer has plummeted to a fifth of its initial incidence. Anal cancer, however, has been rising, with a predilection for human immunodeficiency virus-infected men. HPV causes a squamous epithelial dysplasia and converts healthy tissue into AINs of increasing severity until anal cancer manifests. CLINICAL CASE: This article describes a clinical case of anogenital HPV infection refractory to medical and surgical therapy. It also describes an effective surgical excision technique associated with a good cosmetic outcome. CONCLUSIONS: The paper concludes by briefly discussing the implications of a national screening programme against AIN in the future.

Managing ureteric colic in a smaller hospital without urological support.

No official guidelines exist on managing ureteric colic in small hospitals without urological support. We reviewed the logistics of managing this condition by examining all cases of ureteric colic over two years. Seventy nine of 118 cases had hydronephrosis; a criteria for urology referral. Thirty nine patients passed their stone spontaneously but 40 of these cases could not and required transfer. Twenty two (55%) patients were transferred (mean time to transfer: 3.29 days). The other 18 (45%) were discharged to await a urology outpatients clinic (mean time to discharge: 3.00 days). Patients that passed their stone spontaneously generally had stones under 5mm (mean stay: 2.09 days). We would recommend that patients with stones over 5mm or with hydronephrosis be referred immediately to prevent urological sepsis and or renal impairment.

Acute copper toxicity following copper glycinate injection.

We present a patient who developed multi-organ failure due to severe copper toxicity following attempted suicide by s.c. injection of copper glycinate. Acute copper toxicity is rare in the developed world, although it occurs more frequently in developing world countries, where it is a common mode of suicide. Acute toxicity usually results from oral ingestion and there are several local and systemic effects. Specific management can be difficult as there is little evidence regarding the efficacy of chelating agents in acute toxicity.

The management of basal cell carcinomas.

The mortality and morbidity associated with basal cell carcinoma (BCC) is low. However, BCCs represent a significant burden to the health service due to their high and increasing incidence. This audit was designed to examine the management of BCCs by a dermatology department and to highlight deficiencies in the service offered to patients. The mean intervals between the first dermatology clinic visit and definitive treatment by the dermatology and the plastic surgery departments were 62 and 129 days respectively. Factors contributing to the delay included the frequent use of diagnostic incisional biopsies and the high referral rate from dermatology to the department of plastic and reconstructive surgery. In 90% of cases the dermatologist made an accurate clinical diagnosis. Despite this, diagnostic biopsies were performed in 72% of cases, often necessitating additional hospital visits. Forty three percent of cases were treated definitively by dermatology, whereas over 50% were referred to the department of plastic surgery. A number of changes are planned or are in process as a consequence of the audit.

Synthesis and biological evaluation of 17beta-alkoxyestra-1,3, 5(10)-trienes as potential neuroprotectants against oxidative stress.

17beta-O-Alkyl ethers (methyl, ethyl, propyl, butyl, hexyl, and octyl) of estradiol were obtained from 3-O-benzyl-17beta-estradiol with sodium hydride/alkyl halide, followed by the removal of the O-benzyl protecting group via catalytic transfer hydrogenation. An increase compared to estradiol in the protection of neural (HT-22) cells against oxidative stress due to exposure of glutamate was furnished by higher (C-3 to C-8) alkyl ethers, while methyl and ethyl ethers decreased the neuroprotective effect significantly. Lipophilic (butyl and octyl) ethers blocking the phenolic hydroxyl (3-OH) of A-ring were inactive.

Serine/threonine phosphatases of the pufferfish, Fugu rubripes.

The compact genome of the Japanese pufferfish, Fugu rubripes, about 7.5 times smaller than the human genome, facilitates the isolation of vertebrate genes. We have used this genome to isolate and characterize members of the vertebrate serine/threonine protein phosphatase gene family. Our data reveal the presence of two isoforms of PP2A, alpha and beta, and PPX, as previously found in mammals.

Alternative splicing in a novel tyrosine phosphatase gene (DPTP4E) of Drosophila melanogaster generates two large receptor-like proteins which differ in their carboxyl termini.

A novel Drosophila receptor-like protein tyrosine phosphatase gene, DPTP4E, was isolated and characterized. DPTP4E, located at cytological position 4E1-2, is comprised of 10 exons; its RNA products are widely expressed during embryonic development, including the developing central nervous system. DPTP4E produces three major developmentally regulated transcripts of 6.5, 7.0, and 7.5 kilobases. The two major embryonic transcripts arise as the result of the alternative splicing of exon IX; as a consequence, two proteins (200 and 183 kDa) are produced which differ in their carboxyl-terminal sequences. The deduced extracellular domain, which lies between two putative hydrophobic transmembrane segments, contains 11 fibronectin type III-like repeats and 25 putative N-glycosylation sites. A single conserved protein tyrosine phosphatase (PTPase) catalytic domain, which shows a high level of amino acid identity to the Drosophila PTPase DPTP10D and human HPTP beta, is found in the predicted intracellular domain; this PTPase domain, when expressed as a fusion protein in Escherichia coli, exhibits PTPase activity. The possible implications of these findings are discussed.

Two Drosophila receptor-like tyrosine phosphatase genes are expressed in a subset of developing axons and pioneer neurons in the embryonic CNS.

Two Drosophila receptor-like tyrosine phosphatase genes, DPTP99A and DPTP10D, were characterized. Protein products of these genes show distinct expression patterns specific to subsets of developing CNS axons. DPTP99A expression coincides with the onset of axonogenesis and is expressed in several pioneer neurons, including aCC and RP2, which pioneer the intersegmental nerve; its proteins are transiently expressed in the intersegmental and segmental nerves, arguing for a role in the establishment of these nerves. Both genes produce complex sets of transcripts, owing to the alternative utilization of exons and polyadenylation sites. Each gene produces alternative protein forms, which differ in their C-terminal tails. The deduced proteins possess extracellular FN-III repeats and intracellular PTPase domain(s). We discuss the implications of these results and the role of protein tyrosine dephosphorylation in axon outgrowth and guidance.

Multiple levels of regulation of megakaryocytopoiesis.

A working hypothesis for the regulation of megakaryocytopoiesis is described on the basis of current data. The hypothesis proposes that in vivo megakaryocytes are generated by 1) the expansion of clonable progenitor cells into immature megakaryocytes by locally produced (and regulated) interleukin-3 (IL-3) and 2) the development and maturation of immature megakaryocytes by a dual system; by a lineage specific mechanism involving thrombopoietic stimuli in the steady state and thrombocytopenic conditions, and by a lineage nonspecific mechanism via IL-3 in damaged or reconstituting marrow. The hypothesis predicts that if IL-3 is a significant in vivo regulator of megakaryocyte formation and development, receptor for IL-3 should be present on megakaryocytes and may be vestigially on platelets. Small but significant levels of 125I IL-3 were found to bind to platelets from normal mice. The level of binding on platelets was found to be enhanced sevenfold from mice that had received high levels of irradiation followed by bone marrow transplantation. This contrasted with a twofold increase in the level of binding to platelets from mice made acutely thrombocytopenic with antiplatelet serum. The data suggest that IL-3 may be involved in the in vivo regulation of murine megakaryocytopoiesis and may be a significant factor in rebound thrombopoiesis following bone marrow damage.

Immature megakaryocytes in the mouse: synergistic response to megakaryocyte potentiator, thrombopoietic stimulatory factor with interleukin 3.

The in vitro biological activities of thrombopoietic stimulating factor, recombinant interleukin 3, and megakaryocyte potentiator from various sources were studied. Growth activities were assessed by the responsiveness of enriched populations of small, immature megakaryocytes to factor preparations by measuring increased numbers of acetylcholinesterase-positive cells and increased cell size as indices of megakaryocyte development. All factors stimulated optimum megakaryocyte growth at high concentrations. Immature megakaryocytes revealed the same responsiveness to titrated amounts of the various factors tested, with similar slopes to the dose-response curves. The activities of both thrombopoietic stimulating factor and megakaryocyte potentiator were additive when suboptimal doses were used. In contrast, low concentrations of recombinant interleukin 3 and thrombopoietic stimulating factor acted synergistically to stimulate an optimal response. The data indicate that at low and perhaps physiologically relevant concentrations, two classes of factors influence murine megakaryocyte development by different but related mechanisms.