Osteonecrosis of the Jaw in Patients Receiving Bone-Targeted Therapies: An Overview--Part I.

Urologic patients receiving bone-targeted therapies are at risk of developing osteonecrosis of the jaw (ONJ). ONJ has historically been associated with bisphosphonate therapy. More recently, RANK-Ligand inhibitors (denosumab) have also been used to reduce the risk of skeletal-related events in patients who have advanced cancers with bone metastases. More than 65% of men with metastatic prostate cancer and nearly 75% of women with metastatic breast cancer are affected by bone metastases. The literature has described ONJ associated with bisphosphonate therapy as bisphosphonate-related osteonecrosis of the jaw (BRONJ). However, with evidence also linking the use of RANK-Ligand inhibitors with osteonecrosis of the jaw, we advocate use of the term "anti-bone resorption therapy-related osteonecrosis of the jaw" (ABRT-ONJ). The term "medication-related osteonecrosis of the jaw" (MRONJ) is now becoming more widespread. There is not a universally accepted definition of ABRT-ONJ, which may have hindered recognition and reporting of the condition. In Part I of this article, a review of current knowledge around the etiology of ABRT-ONJ and incidence data are provided. In Part II, we provide an audit of ONJ in a nurse consultant-led bone support clinic. In the article, we refer to zoledronic acid because this is the bisphosphonate of choice for use in men with prostate cancer in the United Kingdom.

Retrospective Audit: Does Prior Assessment by Oral and Maxillofacial Surgeons Reduce the Risk of Osteonecrosis of The Jaw in Patients Receiving Bone-Targeted Therapies for Metastatic Cancers to the Skeleton?--Part II.

Men who receive bone-targeted therapy for metastatic prostate cancer are at increased risk of osteonecrosis of the jaw (ONJ). Development of ONJ has been associated with the administration of bone-targeted therapies in association with other risk factors. ONJ can be distressing for a patient because it can cause pain, risk of jaw fracture, body image disturbance, difficultly eating, and difficulty maintaining good oral hygiene. The aim of this article is to report results of an audit of prior assessment by oral and maxillofacial surgeons (OMFS) before initiation of bone-targeted therapies and whether it may reduce the risk of ONJ in patients receiving bone-targeted therapies for advanced cancers.

Skeletal Health Part 2: Development of a Nurse Practitioner Bone Support Clinic for Urologic Patients.

Part 1 of this article highlighted the potential negative effects of cancer on the skeleton and provided an overview of available treatment options. Part 2 presents a nurse practitioner-led Bone Support Clinic, which was developed for patients with cancer-induced bone disease and cancer therapy-induced bone loss. This clinic, started in 2011 in a university medical center urology/oncology outpatient center in London, England, United Kingdom, has been a collaborative effort among a multidisciplinary team of doctors, nurse practitioners and nurses. Patients have responded positively to the improved continuity of care, and we have been able to assess and treat impending skeletal-related events in a more timely manner The needs of our patient population and problems with the existing service are reviewed, and the importance of a multidisciplinary approach to these problems is discussed. Initiation of a nurse practitioner-led Bone Support Clinic and the impact of timely response to the effects of cancer and cancer therapies on the skeletal system are outlined and offered as a model.

Skeletal Health Part 1: Overview Of Bone Health and Management In the Cancer Setting.

Cancer-induced bone disease and cancer therapy-induced bone loss are significant skeletal problems related to the treatment for urological and other cancers. Our team of specialists and nurse practitioners developed a nurse practitioner-led Bone Support Clinic for urologic cancer patients at a university hospital in London, England, United Kingdom, to address this issue. The clinic has been well-accepted, has made a positive impact on the patient journey, helps to ensure continuity of care, and highlights patients who require assessment or treatment for impending skeletal-related events in a timely fashion. This article has been divided into two parts for improved readability.

Ciprofloxacin Resistance: A Review of Patients in East London Undergoing Prostate Biopsy.

Transrectal ultrasound guided biopsy of the prostate remains the gold standard investigation to diagnose prostate cancer. Although post-biopsy complications are relatively rare, the risk of sepsis associated with the procedure means that prophylactic antibiotics are paramount. The most widely used antibiotic regimen includes a quinolone, such as ciprofloxacin. Resistance to quinolone antibiotics is rising. In this small pilot study, the incidence of quinolone resistance was 18% in our population of patients attending the prostate biopsy clinic.

Effects of psychological stress on male fertility.

Psychological stress can be defined as any uncomfortable 'emotional experience' accompanied by predictable biochemical, physiological and behavioural changes or responses. Many clinical studies looking at the effects of psychological stress on male fertility have shown that stress is associated with reduced paternity and abnormal semen parameters. Enough scientific evidence exists to suggest that psychological stress could severely affect spermatogenesis, mainly as a result of varying testosterone secretion. The hypothalamic-pituitary-adrenal axis has a direct inhibitory action on the hypothalamic-pituitary-gonadal (HPG) axis and Leydig cells in the testes. The newly discovered hormone, gonadotropin-inhibitory hormone (GnIH), also has an inhibitory effect on the HPG axis. Inhibition of the HPG axis results in a fall in testosterone levels, which causes changes in Sertoli cells and the blood-testis barrier, leading to the arrest of spermatogenesis. Germ cells also become vulnerable to gonadotoxins and oxidation. However, the extent and severity of the effects of psychological stress on human testes is difficult to study and data mostly come from animal models. Despite this limitation, stress as a causative factor in male infertility cannot be ignored and patients should be made aware of its effects on testicular function and fertility and helped to manage them.

Management of non-muscle-invasive (superficial) bladder cancer.

Non-muscle-invasive (superficial) bladder cancer (NMIBC) represents 80% of incident cases of bladder cancer, and is characterized by a generally good prognosis, with a tendency to remain localized. Only 10%-20% of cases progress to invasion and/or metastasis. The biggest problem in management is the potential for local recurrence, and this will occur with relatively predictable prognostic determinants. Gene expression and other cell surface determinant are associated with outcome. In most cases, successful management is predicated on careful history taking and physical assessment, meticulous endoscopic assessment, and transurethral resection of bladder tumor tissue where indicated. Histology determines the potential for recurrence. Options of treatment include repeat resection, immunologic therapy via intravesical instillation, and the use of intravescally administered cytotoxic agents, including mitomycin C, doxorubicin, gemcitabine, and selected investigational compounds. Of importance, as some cases have the potential to invade and metastasize, timing of cystectomy for recurrent, high-risk tumors is important to avoid unnecessary morbidity and mortality.

Radical prostatectomy--too soon to abandon the perineal approach?

Perineal radical prostatectomy (PRP) is one of the oldest surgical procedures for prostate cancer, but its use has declined over the past 30 years. New studies show that PRP is not only minimally invasive but beneficial from an economic perspective and should not yet be abandoned in the treatment of early prostate cancer.

Clinical management of chronic testicular pain.

AIM: To review the causes and principles and recent concepts in the management of testicular pain. INTRODUCTION: Chronic testicular pain is a common presenting symptom in genitourinary surgery. Due to increased awareness of testicular cancer and in men's health more cases are likely to be referred. MATERIAL AND METHODS: A literature search was made for abstracts, original papers and review articles in the Cochrane Database, Medline and medical textbooks using the words 'testicular pain' and orchialgia to find the causes and mechanisms of testicular pain. The management and algorithm have been structured on evidence-based management strategies. RESULTS: The management of chronic testicular pain remains essentially based on clinical assessment. In recent years there have been advances in the non-surgical management of testicular pain mainly because of the emergence of pain relief as a specialty. However, in some cases pain control is a problem and may ultimately conclude with orchiectomy. CONCLUSIONS: The management of chronic testicular pain includes a careful assessment of testicular and extratesticular causes. Relief of symptoms is not always possible and gaining an insight into the patient's concerns and empathizing with their condition is paramount in helping them cope with their symptoms. Surgery should not be undertaken lightly for there is no guarantee that there will always be resolution of symptoms and the patient should be counseled accordingly.

The risk of prostate cancer amongst South Asian men in southern England: the PROCESS cohort study.

OBJECTIVE: To reinvestigate whether South Asian men in the UK are at lower risk of being diagnosed with prostate cancer in a UK-based retrospective cohort study and to examine possible reasons that may explain this. PATIENTS AND METHODS: The catchment areas were predefined in four areas of southern England, and age- and race-specific populations for those areas taken from census data. Cases were ascertained through review of multiple hospital sources, while race, other demographic factors, and medical history were determined using questionnaires sent to the men, hospital records review and death certificates. The South Asian group included men of Indian, Bangladeshi and Pakistani origin. RESULTS: There was modest evidence of lower prostate cancer rates in South Asian men compared with their White neighbours (age-adjusted rate ratio 0.81; 95% confidence interval 0.65-1.00). This difference did not reflect less use of prostate-specific antigen (PSA) testing or differences in clinical features at presentation. CONCLUSION: This study provides evidence of a lower incidence of prostate cancer amongst South Asian men living in England, in comparison with their White counterparts. If anything, South Asian men presented with clinical features of earlier disease suggesting that the reduced risk is unlikely to be an artefact of poorer access to health care.

Tamsulosin MR and OCAS (modified release and oral controlled absorption system): current therapeutic uses.

BACKGROUND: Although tamsulosin is mainly used to treat lower urinary tract symptoms secondary to benign prostatic hyperplasia, with better understanding of functional anatomy and distribution of alpha(1) receptors, it is also indicated in other conditions of genito-urinary tract in both men and women. OBJECTIVE: To detail the therapeutic use and clinical effects of tamsulosin. METHODS: The scope of the review was related to tamsulosin and its therapeutic application in conditions of genitourinary tract. Publications were searched from Pubmed and Medline from 1975 to 2007 using the search words tamsulosin, lower urinary tract symptoms, alpha receptors and blockers. CONCLUSIONS: The management of benign prostatic hyperplasia was transurethral resection of prostate until simpler and alternative treatments were tried in the last two decades, particularly alpha(1) adrenoceptor-blocking agents. Tamsulosin is a potent, third-generation selective alpha(1A) adrenoceptor-blocking agent.

Stage migration and pilot studies of reduced chemotherapy supported by positron-emission tomography findings suggest new combined strategies for stage 2 nonseminoma germ cell tumour.

OBJECTIVE: To examine the nodal (N+) vs extranodal (M+) staging in each of the International Germ Cell Consensus Classification Group (IGCCCG) subgroups in an audit of 437 patients treated in The Anglian Germ Cell Cancer Group, where chemotherapy was the primary management, as there is an increasingly earlier presentation of patients with less advanced disease who thus face potentially unnecessary treatment. PATIENTS AND METHODS: Clinicians from seven centres prospectively registered patients in a central database, and the follow-up was coordinated by one of the authors. RESULTS: Between 1982 and 2002, 436 patients (median follow-up 60 months) were registered; 63% of IGCCCG good risk (298), 42% of intermediate (62) and 8% poor risk (77) were stage II; 79% of N+M0 intermediate and poor risk cases (29) were alive, vs only 60% of M+ stage IV cases (92, P < 0.05). The trend was similar in IGCCCG good risk patients, with 92% of N+ stage II (156) alive vs only 85% (94) of stage IV M+ (not significant). The frequency of retroperitoneal lymph node dissection after chemotherapy increased from 26% (1983-1993) to 34% (1994-2002), and survival from 89% to 94%. There were no relapses in eight patients who elected to stop treatment after two courses. Four of six patients with positive findings on positron emission tomography had a durable complete response, assessed by standard uptake values, when tested at 72-96 h. CONCLUSION: Extra-lymphatic spread, although prognostically important within the IGCCCG subgroups, is only statistically significant for intermediate and poor risk combined. The observation that there might be N+ patients cured by two chemotherapy courses alone suggests that there might be opportunities to reduce the morbidity of treatment.

The risk of prostate cancer amongst black men in the United Kingdom: the PROCESS cohort study.

OBJECTIVES: It is known that African American men have a greater risk of prostate cancer than white men. We investigated whether this was true for first-generation black Caribbean and black African men in the United Kingdom. METHODS: A clinical cohort study design recruiting all cases of prostate cancer diagnosed over a 5-yr period and residing in defined areas of London and Bristol. We calculated the age-standardised incidence rates and relative risk for all black men, and black Caribbean and black African men versus white men. RESULTS: Black men had higher age-adjusted rates of prostate cancer (166 per 100,000, 95% confidence interval [95%CI], 151-180 per 100,000) than white men (56.4 per 100,000, 95%CI, 53.3-59.5 per 100,000). The relative risks for all black, black Caribbean, and black African men were 3.09 (95%CI, 2.79-3.43; p<0.0001), 3.19 (95%CI, 2.85-3.56; p<0.0001) and 2.87 (95%CI, 2.34-3.53; p<0.0001), respectively. There was no strong evidence that the rates for black Caribbean differed from black African men. The higher risk in black men compared with white men was more apparent in younger age groups (p value for interaction<0.001). CONCLUSIONS: Black men in the United Kingdom have substantially greater risk of developing prostate cancer compared with white men, although this risk is lower than that of black men in the United States. The similar rates in black Caribbean and black African men suggest a common genetic aetiology, although migration may be associated with an increased risk attributable to a gene-environment interaction.

Haematuria 2: Imaging investigations, management and follow up.

Haematuria is a common complaint presenting to doctors in both primary and secondary care. It can be a sign of underlying urinary tract malignancy. Appropriate investigation and management should follow evidence-based practice and recognized guidelines, and subsequently lead to a rapid diagnosis.

Management of post-radical prostatectomy anastomotic stricture by endoscopic transurethral balloon dilatation.

OBJECTIVE: Anastomotic strictures are seen more commonly with increasing treatment of prostate cancer by means of radical prostatectomy. In view of the proximity to the sphincter, anastomotic strictures need careful management to avoid making the patient incontinent. We describe our experience with a novel method. MATERIAL AND METHODS: Nine patients who had developed anastomotic strictures were treated with endoscopic transurethral balloon dilatation. A catheter was left in place for 24 h postoperatively. RESULTS: Eight patients were treated successfully and remained well after a median follow-up period of 33 months. There were no complications and all patients remained continent. CONCLUSION: This is a safe and effective procedure that should be used as a first-line treatment for the management of anastomotic strictures, with transurethral incision being reserved for non-responders.

Haematuria 1: risk factors, clinical evaluation and laboratory investigations.

Haematuria is a common complaint presenting to doctors in both community and acute centres. It can be a sign of underlying urinary tract malignancy. Appropriate investigation and management should follow evidence-based practice and recognized guidelines, and subsequently lead to a rapid diagnosis.

Risk and presenting features of prostate cancer amongst African-Caribbean, South Asian and European men in North-east London.

OBJECTIVE: To determine whether there are ethnic differences in the incidence and presenting features of all patients with prostate cancer presenting in North-east London, UK. PATIENTS AND METHODS: All newly diagnosed men with prostate cancer between 1999 and 2000 who were resident in the East London and City Health Authority were identified from various sources. Key clinical features were extracted from hospital records. The age-adjusted incidence rates for European, South Asian and African-Caribbean patients were calculated using census denominator data. RESULTS: For men aged >50 years the annual age-adjusted incidence rates (95% confidence interval) were 213 (186-240), 647 (504-789) and 199 (85-310) for the European, African-Caribbean and South Asian patients, respectively. African-Caribbean men had a three times greater risk (risk ratio 3.07, 2.40-3.93, P < 0.001) than European men. South Asian men had a lower risk of prostate cancer but this could have been compatible with chance. There was no evidence of marked ethnic differences for prostate-specific antigen levels, clinical staging and Gleason scores. CONCLUSION: The greater risk of prostate cancer for African-Caribbean men in South-east England is consistent with data from the USA and the Caribbean. Future work needs to determine whether this risk differs according to country of origin, and which genetic and/or environmental risk factors might be important in explaining these observations.