Specialist Registrar, Department of Urology, Kingston Hospital, Surrey, UK & Honorary Lecturer in Urology, Postgraduate Medical School, University of Surrey, UK
sooriakumaran@gmail.com
Prasanna Sooriakumaran (or PS for short!) obtained his BMedSci in the First Class and his medical degree With Honours from the University of Nottingham. He underwent his postgraduate surgical training in London obtaining his MRCS on first attempt in 2003. He then undertook a PhD in Prostate Cancer at the University of Surrey and became a Specialist Registrar in Urology on the South Thames Rotation in April 2006. Later that year he completed a Postgraduate Certificate in Medical Law from the University of Glasgow. PS currently works at Kingston Hospital and has also recently been made an Honorary Lecturer in Urology at the University of Surrey. PS has published 31 papers in indexed medical journals and also presented his research at over 80 international conferences. He has written two books and one book chapter, been an advisor for a further book, and reviewed for many international journals. PS has won ten postgraduate prizes and awards, and been nominated for a further six, for his research, teaching, and clinical contributions.
Abstract: The doctor-patient relationship has undergone a transition throughout the ages. Prior to the last two decades, the relationship was predominantly between a patient seeking help and a doctor whose decisions were silently complied with by the patient. In this paternalistic model of the doctor-patient relationship, the doctor utilises his skills to choose the necessary interventions and treatments most likely to restore the patient's health or ameliorate his pain. Any information given to the patient is selected to encourage them to consent to the doctor's decisions. This description of the asymmetrical or imbalanced interaction between doctor and patient [Parsons T. The social system. Free Press, New York, 1951.](1) has been challenged during the last 20 years. Critics have proposed a more active, autonomous and thus patient-centred role for the patient who advocates greater patient control, reduced physician dominance, and more mutual participation. This patient-centred approach has been described as one where "the physician tries to enter the patient's world, to see the illness through the patient's eyes" [McWhinney I. The need for a transformed clinical method. In: Stewart M, Roter D, Communicating with medical patients. London: Sage, 1989.](2), and has become the predominant model in clinical practice today.
Abstract: There is mounting evidence to support a role for cyclooxygenase-2 (COX-2) inhibitors (coxibs) in the management of prostate cancer. This review considers the current evidence base for the use of coxibs in prostate cancer as well as their adverse event profile. A systematic literature review using the search terms 'cyclooxygenase', 'COX-2', 'coxibs', 'cardiovascular risk', and 'prostate cancer' was performed using Medline. Celecoxib appears safer in terms of cardiovascular toxicity than other coxibs, and this may relate to its lower selectivity for the COX-2 enzyme. This lower selectivity also provides rationale for its putative broader anti-cancer effects, via non-COX-2-dependent pathways that affect cell cycle regulation, angiogenesis, and hypoxic modulation. There are also interacting relationships between COX-2, chronic inflammation, and prostate cancer. There is much promise for the coxibs as anti-cancer agents. The future might be to pharmacologically adapt these agents to exert their COX-2 independent mechanisms of action while minimizing their COX-2-dependent adverse cardiovascular effects.
Abstract: OBJECTIVE: To report our clinical experience and 5-year prostate-specific antigen (PSA) relapse-free survival rate for early-stage prostate cancer after (125)I low-dose-rate prostate brachytherapy. PATIENTS AND METHODS: In all, 300 patients were treated between March 1999 and April 2003, and followed prospectively. Patients were stratified into low-, intermediate- and high-risk groups, and those receiving neoadjuvant androgen deprivation (NAAD) or not. Kaplan-Meier estimates of PSA relapse-free survival and PSA nadirs were obtained for all patients and for the risk groups. Toxicity, as urinary and erectile dysfunction (ED), were reported from a prospective database. RESULTS: The median (range) follow-up was 45 (33-82) months. The actuarial PSA relapse-free survival was 93% at 5 years; 21 (7%) of patients had evidence of biochemical failure as defined by the American Society of Therapeutic Radiation Oncology criteria. There was no significant difference in actuarial survival for patients in the different risk groups, or between those receiving NAAD or not (low-risk 96%, intermediate 89%, high 93%, P = 0.12; NAAD 92%, no NAAD 95%, P = 0.30). Overall the 3-year median PSA level was 0.3 ng/mL (192 men). There was no significant difference in median 3-year PSA levels for different risk groups, or for those treated with or with no NAAD. The 3- and 4-year PSA nadir of <0.5 ng/mL was achieved by 71% and 86% of men, respectively. The acute urinary retention rate was 7%; 5.6% of men developed urethral strictures requiring dilatation, while 2.7% required a transurethral resection of the prostate after implantation, for obstructive symptoms. Of patients with no ED before treatment, 62% had no ED at 2 years, and of these 60% used a phosphodiesterase inhibitor. CONCLUSION: This prospective series confirms the excellent overall biochemical survival after (125)I brachytherapy; the treatment was tolerated well, with early and late urinary toxicity and ED similar to other published results.
Abstract: Prostate cancer is the most prevalent nondermatological malignancy affecting men in the Western world. An increase in public awareness has led to earlier detection. Accepted treatments for localized prostate cancer include active surveillance, radical prostatectomy, interstitial brachytherapy, external beam radiotherapy and watchful waiting. The authors discuss the rationale for the different approaches together with outcomes including toxicity. Novel approaches are also explored. The management of locally advanced disease has long been a challenge and the evolving evidence is reviewed.
Abstract: Numerous agents have been investigated in prostate cancer prevention. Many manipulate sex steroid levels or function, some regulate response to oxidative stress and others affect tumor proliferation and/or apoptosis. Some are postulated to even affect downstream targets, such as cyclooxygenase-2, which has been shown to be elevated in prostate cancer by most investigators. The evidence for all these potential chemopreventive agents is critically reviewed. While the current information base is vast, level 1 evidence is lacking, and ongoing trials are not due to provide such evidence for many years to come. In addition, the current lack of ability to accurately differentiate clinically important prostate cancer from latent disease makes chemoprevention in this setting even more challenging. Currently, no reliable biomarkers that can act as surrogate endpoints for the development of clinically relevant prostate cancer exist, which makes performing large chemoprevention trials expensive. At present, there is little to suggest that the urologist or General Practitioner should be recommending any particular chemopreventive agent to either the general population or those deemed to be at higher risk of contracting prostate cancer.
Abstract: The selective COX-2 inhibitors (coxibs) were originally developed to minimise the adverse effects of conventional non-steroidal anti-inflammatory drugs (NSAIDs) while maintaining the same analgesic and anti-inflammatory properties. Many large studies confirmed the improved gastric side effect profile of coxibs compared with non-selective NSAIDs; however, reports of increased cardiovascular morbidity and mortality followed, and the manufacturer Merck was forced to withdraw rofecoxib (Vioxx) from the market. Other coxibs have also either perished or had restrictions placed on their use. However, there seem to be significant differences between coxibs regarding their cardiovascular profiles, and the evidence for a class effect is dubious. In this paper, the current body of knowledge regarding the cardiovascular toxicities of coxibs is reviewed. The take home message for prescribing NSAIDs and those coxibs still on the market seems to be one of caution rather than contraindication, except in patients with significant cardiovascular risk factors.
Abstract: Despite the increased detection of prostate cancer at an early stage, men are still dying of this disease. Management of advanced disease focuses on controlling the disease process, palliation of symptoms and improving quality of life. In this review, the basis for androgen deprivation in hormone-dependent disease is discussed and the role of maximum and intermittent androgen deprivation, as well as management options for hormone-refractory disease is addressed. Local radiotherapy continues to be of importance in pain control and the maintenance of quality of life. Radiopharmaceuticals and bisphosphonates also have a role to play, the latter particularly in the reduction of skeletal-related events. Chemotherapy in hormone-refractory disease is now well established following pivotal trials demonstrating a survival benefit with docetaxel. The emergence of novel agents targeting growth factors, angiogenesis and immunotherapy present exciting possibilities for future treatment.
Abstract: AIM: To investigate the causes and costs of flexible ureteroscope damage, and to develop recommendations to limit damage. METHODS: The authors analysed repair figures and possible causes of damage to 35 instruments sent for repair to a leading UK supplier over a 1-year period, and calculated cost figures for maintenance of the instruments as opposed to repair and replacement costs. RESULTS: All damages were handling-induced and therefore did not fall under the manufacturer's warranty: 28 % were damaged by misfiring of the laser inside the instrument; 72 %, mainly crushing and stripping of the ureteroscope shaft tube, were likely to have occurred during out-of-surgery handling, washing and disinfection. Seventeen (4 %) instruments were not repaired and consequently taken out of service due to the extensive costs involved. Eighteen (51 %) ureteroscopes were repaired at an average cost of 10 833 USD. CONCLUSION: Damages to flexible ureteroscopes bear considerable costs. Most damages occur during handling between surgical procedures. Thorough adherence to handling procedures, and courses for theater staff and surgeons on handling flexible instruments may help to reduce these damages and prove a cost-saving investment. The authors provide a list of recommended procedural measures that may help to prevent such damages.
Abstract: Cyclo-oxygenase (COX), also referred to as prostaglandin (PG) endoperoxidase synthase, is a key enzymatic mediator in the production of arachidonic acids to PGs and eicosanoids. Two isoforms of COX exist, namely COX-1 and COX-2, which have distinct physiological functions and tissue distribution. Epidemiological studies suggest that regular consumption of aspirin and/or other non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit COX, could notably reduce the risk of developing many cancers. COX-2 expression has been shown to increase in many cancers and cancer cell lines, including human prostate adenocarcinoma. COX-2 may also be upregulated in proliferative inflammatory atrophy (PIA) of the prostate, a pre-neoplastic lesion. The COX-2 pathway may therefore be a useful target for chemoprevention of prostate cancer, and there is much interest in exploring this with the use of COX-2 inhibitor drugs such as celecoxib. While there is concern regarding the cardiovascular toxicities of coxibs, there is no evidence that there is any increased risk with the use of celecoxib in the short-term neoadjuvant setting.
Abstract: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in hospitalised patients. Thromboprophylaxis is an effective strategy for VTE prevention in high-risk patients. An initial audit in our district general hospital trust showed poor adherence to the thromboembolic risk factors consensus group recommendations and so a risk assessment form (RAF) was devised. We present repeated audits to assess the RAF uptake and its effects on VTE thromboprophylaxis. We also present data analysing perceptions among doctors of the RAF and reasons for its poor completion. We provide compelling evidence that the RAF is an invaluable tool in the assessment of VTE thromboprophylaxis.
Abstract: AIM AND METHODS: A retrospective review was carried out of children undergoing peritoneovenous shunting for intractable ascites. RESULTS: 11 children, aged 3 months to 12 years (median 31 months) underwent peritoneovenous shunting over the past 17 years. The duration of ascites ranged from one month to 2.5 years (median two months). The primary pathology consisted of previous surgery in eight (three neuroblastoma, one renal carcinoma, one hepatoblastoma, one adrenal teratoma, one renal artery stenosis, and one diaphragmatic hernia), and cytomegalovirus hepatitis, lymphatic hypoplasia, and lymphohistiocytosis in one patient each. All patients had failed to respond to previous treatment including peritoneal drainage in six patients, diuretics in five, and parenteral nutrition in five. There were no intraoperative problems. Postoperative complications included pulmonary oedema in three patients, shunt occlusion in three, infection in two, and wound leakage in one. Ascites resolved after shunting in 10 patients. Five shunts were removed one to three years after insertion without recurrence of ascites. Three others are free of ascites with shunts in place for less than one year postoperatively. Three children died from their underlying disease: two after resolution of ascites (neuroblastoma) and one in whom the ascites failed to resolve (lymphohisticytosis). CONCLUSIONS: Peritoneovenous shunting is an effective treatment for symptomatic intractable ascites in children (10 of 11 successful cases in this series). Elective removal of the shunt after one year is recommended.
Abstract: Quadratus plantae is a muscle in the sole of the foot, typically originating from the calcaneus and inserting into the posterolateral surface of the tendons of flexor digitorum longus. It is implicated in heel pain, claw toe deformity and diabetic polyneuropathy. Phylogenetic considerations suggest that quadratus plantae is getting bulkier, implying its significance in human locomotion. Is it simply an accessory flexor that brings the line of pull of flexor digitorum longus in line with the long axis of the foot, as its name would suggest? We cite evidence from electromyographic studies that suggest it actually acts as a primary toe flexor in voluntary movements, being preferentially recruited over flexor digitorum longus. From comparative anatomical considerations it also seems likely that quadratus plantae is an intrinsic evertor of the foot. Eversion is an important evolutionary asset, especially in erect bipedalism. Human electromyographic experiments have yet to confirm this. However, they do suggest that quadratus plantae functions to resist extension of the toes during the stance phase of locomotion, which serves to increase the stability of the foot. Future electromyographic experiments may provide more information on the role of quadratus plantae in human locomotor evolution and in foot eversion in particular.
Abstract: Treatment for metastatic testicular cancer has generally met greatest success when it has involved platinum-based chemotherapy and this is widely used for metastatic disease in most centers. However, surgical techniques should not be excluded. Retroperitoneal lymph node dissection has enabled a high cure rate to be achieved when used in conjunction with chemotherapy in patients with more advanced stage cancers.
Abstract: A frequency volume chart is a simple, easy-to-use, non-invasive tool that is useful in the assessment of patients with lower urinary tract symptoms. Though more sophisticated techniques are now available for diagnosis, the frequency volume chart should still be considered the first line investigation. In this review we summarize the indications and value of this age old investigation. Urologists and primary care physicians should use the frequency volume chart more frequently in their practice.
Abstract: AIMS: To investigate whether our practice of specialist review of all diagnostic biopsies was necessary to prevent misgrading of referred prostate cancer patients, and whether this misclassification, if any, would have resulted in misclassification of clinical risk grouping (Seattle Risk Grouping [SRG]) and subsequent treatment strategy and prognosis. MATERIALS AND METHODS: Important prognostic indicators for prostate cancer include the presenting prostate-specific antigen (PSA), clinical stage and Gleason sum of the tumour. These three variables are incorporated into the SRG cohorts to establish treatment strategy. Patients with prostate cancer referred for brachytherapy had their prostate biopsies reviewed by a reference pathologist (PD) with a special interest in prostate cancer. We compared the agreement between the scoring of the referring pathologists with that of PD, and evaluated if any differences changed the SRG and therefore the clinical risk and treatment strategy for the patients. RESULTS: In only 52% (43/83) of cases, was there total agreement between the two sets of pathologists. The inter-rater agreement was statistically 'fair' (unweighted kappa statistic 0.27). In 90% (36/40) of cases with disagreement, PD assigned higher Gleason sums. In 40% (16/40) of cases with disagreement, the change in Gleason sum altered the SRG; in one out of 16 cases, the SRG was downgraded from 'intermediate' to 'low' risk disease; in six out of 16 cases, it was upgraded from 'low' to 'intermediate' risk, and, in nine out of 16, from 'intermediate' to 'high' risk. CONCLUSION: Our findings confirm previous reports of only limited correlation between pathologists in reporting Gleason sums. In this study, 19% (16/83) of cases had their grading changed to a level that altered clinical risk, almost always (94%; 15/16) to one that worsened prognosis. This would have significantly affected treatment strategy for these patients, and thus we recommend that all centres ensure accurate Gleason grading by the use of pathologists with special interests in prostate cancer.
Abstract: AIMS: To investigate the value of the modified Alvarado score (MAS) in helping Accident & Emergency (A&E) doctors decide which patients with suspected acute appendicitis need surgical referral. METHODS: 11,258 patients presented to a University Hospital A&E Department over a two-month period; 82 were triaged as 'abdominal pain' or 'suspected appendicitis'. Ten patients self-discharged prior to seeing a doctor. The remaining case notes (72) were reviewed and MAS's calculated. The Alvarado guidelines suggested an MAS > or = 5 (high) needed admission and an MAS < 5 (low) excluded appendicitis and was appropriate for discharge. RESULTS: Two patients had proven pancreatitis and were excluded. 24/70 patients were admitted for suspected appendicitis; all were referred by the A&E doctor (sensitivity 100%) but only 12 had a high MAS (sensitivity 50%). Twelve patients were therefore admitted despite having a low MAS on retrospective analysis. 46/70 patients were discharged (none re-presented with the same complaint) of which 40/46 were sent home without surgical referral (specificity 87%), but only 44/46 patients discharged had a low MAS (specificity 96%). CONCLUSIONS: It is more important to refer every case that needs referral (sensitivity) than to discharge those not needing referral (specificity). We cannot exclude the possibility that morbidity would result were the MAS used in lieu of clinical judgment in deciding whether referral is necessary in cases of suspected acute appendicitis.
Abstract: The formation of new blood vessels, angiogenesis, is a highly-regulated active process that is critical for the development of the normal and malignant prostate. The vascular endothelial growth factor (VEGF) system assumes a critical role in the angiogenic process. Angiogenesis is a prerequisite for the expansion of solid tumours beyond 1-3 mm3 and is stimulated in response to a hypoxic environment. This review discusses the process of angiogenesis and the key angiogenic mediator, VEGF, and their role in tumour progression and metastasis. A better understanding of the mechanisms behind angiogenesis will ultimately lead to the development of new anti-angiogenic agents in the management of prostate cancer.
Abstract: The medial patellofemoral ligament (MPFL) is a condensation of the medial capsule of the knee joint. In the past two decades dissection studies have shown that it extends from the superomedial border of the patella to the femoral epicondyle, at or immediately above the adductor tubercle. MRI and operative studies have revealed that it is almost invariably damaged by lateral patellofemoral dislocation. Current surgical management of such dislocations may involve imbricating the torn medial capsule and parapatellar retinaculum back onto the medial border of the patella. If the medial patellofemoral ligament is torn at or near the femoral attachment, as the latest MRI and operative studies demonstrate it frequently is, then this medial reefing procedure will not be successful in restoring normal anatomy and function. Here we review the anatomy and function of the MPFL, its role in patellar dislocation and as well as surgical treatment for patellar dislocation.
Abstract: Toxicity of compounds requiring glutathione for detoxification, thiol content and synthesis were determined in 24-h rat hepatocytes cultured in medium containing different concentrations of the sulphur amino acids. Glutathione synthesis was determined following prior depletion of glutathione with diethylmaleate. L-15 medium, which has high levels of cysteine and methionine (1 mM of each), provided some protection against dichloroacetone, dibromopropanol and dichloropropanol toxicity, and had a small effect on increasing glutathione content and synthesis, relative to Williams' medium E (WE) which has low levels (less than 0.5 mM) of both amino acids. However, WE containing N-acetylcysteine (NAC) (1 mM final cysteine concentration), with or without methionine (final concentration 1 mM), was a better cytoprotectant medium than L-15, markedly reducing toxicity of all three compounds, and rapidly (within 1.5 h) increasing cellular glutathione content. WE supplemented with methionine alone stimulated glutathione synthesis after an initial lag phase, and protected cultures against dichloropropanol, but not dibromopropanol or dichloroacetone, both of which are highly reactive in these cultures. There was a clear association between glutathione content at early time points in culture and toxicity observed at later time points, and overall these results indicate that differences in culture medium composition can alter intracellular glutathione content and xenobiotic toxicity.
