IAUN Conference Dublin, January 2014 Helen Forristal Cancer Nurse Co- Ordinator Jonathan Borwell Bladder Cancer Clinical Nurse Specialist
Theoretical component Observation Supervised practice Assessment Independent practice
Bladder Pain Syndrome/Interstitial Cystitis Difficult diagnosis (need to exclude other pathology) Repeated urinary tract infections (UTIs) caused by bacteria entering the bladder, resulting in the inflammation and degeneration of the bladder wall - does not respond to conventional antibiotic therapy Chronic pain Altered voiding pattern (e.g. urgency, frequency, nocturia, dysuria Formal rigid cystoscopy Cascade bleeding after cystodistention, Hunner s ulcers
Radiation-induced Cystitis Post pelvic radiotherapy May be delayed for up to 10 years post RT Voiding pattern change Bladder inflammation Haematuria Dysuria Urgency
Rate and severity of RIC Volume and target of radiotherapy Dose rate of RT Total dose of RT
Recurrent Bacterial cystitis >3 UTI episodes per year
: THESE CONDITIONS HAVE A MAJOR IMPACT ON PATIENTS' LIVES (The diagnosis of these conditions is Consultant / Hospital led)
Glycosaminoglycans (GAGs) form the principal protective barrier (the GAG layer) between urine and the bladder epithelium DEFECTIVE GAG LAYER NORMAL GAG LAYER Epithelium protected from urinary irritants by the glycosaminoglycan (GAG) layer Loss of hyaluronic acid and other GAGs The bladder wall is open to harmful irritants resulting in urgency of urination and pain
Products are classified as medical devices Aseptic technique ISC catheter Secondary Care Primary Care Administered by patient
Treatment regimes Held within bladder for minimum of 30 minutes Once weekly for 4-6 weeks Monthly until symptoms resolve Alternate months
extracellular matrix Hyaluronic acid not only provides protection and replenishes the GAG layer, but it also has major moisturising properties. HA is extremely hydrophilic and binds 1000 times its own volume of water thus attracting and holding water in the extracellular matrix
Cystistat 40mg Sodium Hyaluronate
ialuril Hyaluronic Acid (1.6% w/v) Chondroitin Sulphate
Hyacyst Sodium Hyaluronate 40mg/50mls
Newly diagnosed cases of cancer (male and female) in Europe by cancer site (2006 estimates, thousands of people) 1 Bladder cancer represents 90% of all cancers of the urinary tract It is the 5th most common cancer in Europe 1 Fourth most frequent malignancy in men 1 Twelfth most common in women 1 Bladder cancer occurs most frequently in the >50 age group 2 (Adapated from Ferlay, J et al. Ann Oncol 2007; 18:581-592) References 1. Ferlay, J et al. Ann Oncol 2007; 18:581-592 2. Cancer Research UK http://www.cancerhelp.org.uk/help/default.asp?page=2695
Staging
TNM Staging of TCC bladder Superficial T1 invades lamina propria Ta confined to bladder mucosa Tis carcinoma in situ
Silver Nitrate Trichloroacetic acid Podophyllin Thiotepa (Jones and Swinney, Lancet, 1961) Doxorubicin Epirubicin (derivative from Doxorubicin) Mitomycin-C Bacillus Calmette and Guerin
NICE Guidelines, 2002 Improving Outcomes in Urological Cancers. The manual of cancer standards. Recommend a timely instillation of chemotherapy post-resection. www.nice.org.uk www.doh.gov.uk/cancer/cancerplan.html
A single dose of intravesical chemotherapy should be given within 24h of TUR(BT), unless contraindicated. Ideally, within 6 hours of resection (Kaasinen,2002) This may reduce recurrence by up to 50% for up to 2 years after treatment. For intermediate risk group (Multifocal,G1/G2 Ta-T1) may reduce need for further treatment. (Boufioux et al 1995: Tolley et al 1996) EAU Guidelines, 2006,2008,2011,2013
Mitomycin-C Dose = 40mg in 40mls WFI or 0.9% Normal Saline Administered in Theatre Recovery Ward OutPatients
Should be advocated for all patients after TUR(BT) New presentation and recurrent disease Multifocal disease 1 shot not adequate (Kaasinen; Huncharek ; EAU guidelines)
Low-risk tumours Primary, solitary, Ta, G1 (low grade), < 3 cm, no CIS Intermediate-risk tumours High-risk tumours All tumours not defined in the two adjacent categories (between the category of low and high risk) Any of the following: T1 tumour G3 (high grade) tumour CIS Multiple and recurrent and large (> 3 cm) Ta G1G2 tumours (all conditions must be presented in this point) (EAU Guidelines, 2013)
Overview MMC isolated from bacterium in 1956 (Streptomyces Caespitosus) Antibacterial and antitumoral antibiotic Developed as a cytotoxic agent in Japan in 1960 s Widely used since 1962
Modality of action Uptake by epithelial cells. Activated into an alkylating agent which binds to form cross linkage with DNA and RNA Inhibits division of cancerous cells by blocking synthesis of DNA and RNA
Contraindications Excessive haematuria Risk of perforation, peri-operatively Reported cases of extravasation requiring surgical debridement Nieuwenhuijzen et al.,eur Urol 2003;43(6):711-2 Previous reaction to Mitomycin
Consent for courses of chemotherapy or immunotherapy should be obtained on Form 3. Intended benefits + risks documented with appropriate literature.
BCG strains 1908 M.bovis 1931 1961 Pasteur Frappier Tice Glaxo Brikhaug Japan Russia Phipps Connaught Denmark Prague Sweden Moreau
Induces a local response in bladder in 2 phases; Cytokine production Inflammation Neutrophil recruitment Bohle et al. J Urol 2003; 170:964-9 After 2h of instillation neutrophil recruitment Delayed response causing granulomatous inflammation May persist for 2 years post BCG Durek et al J Urol 2001;165:1765-8
Mode of action 1 is believed to be: Attachment of BCG to endothelial cells aided by fibronectin BCG stimulates 2 cells to produce cytokines (cytokines prepare the ground for a cellular assault) 2 1. ImmuCyst 81mg Summary of Product Characteristics 2. Lockyear CRW. and Gillatt D. J.R.Soc Med 2001; 94:119-123 BCG Fibronectin Tumour
4. Lamm DL, Blumenstein BA, Crissman JD et al. J Urol 2000; 163: 1124-1129. 4
Contraindications Pts receiving immunosuppressive therapy Pts with congenital or acquired immune deficiencies Current or previous evidence of a systemic BCG reaction Pts with active tuberculosis Treatment postponed in pts with febrile illness, UTI or macroscopic haematuria Allow 14 days before administering following biopsy, TUR or traumatic catheterisation
Induction & Maintenance Therapy Reduces risk of recurrence or progression Lamm D et al 2000 J Urol 163: 1124-1129 > 1 year maintenance required to gain superiority of MMC in progression and recurrence Bohle Urology 2004 63(4):682-7 Optimal number of induction doses and frequency of maintenance instillations in debate. Zlotta et al Eur Urol 2000 37(4):470-7 Induction courses tend to mirror Morales x6 doses
Intravesical BCG -Adverse Reactions Common adverse reactions: Abacterial Cystitis +/- Dysuria (80%) Urgency Haematuria (40%) Fever <38.5 (30%) Malaise
Less common adverse effects *Allergic skin rashes (<1%) Granulomatous prostatitis (1%) Treated if symptomatic with rifampicin and isoniazid Can be present in liver, lung, kidney *Arthralgia (<1%) Epididymo-orchitis (0.2%) Contracted bladder
Systemic BCG reaction 0.4% BCG-it is/bcg-osis traumatic catheterisation / recent resection high fever (>38.5) can present with impaired haemodynamic status; abnormal LFT s; leukopenia and may lead to multi organ failure Triple therapy; Gram ve AB s and steroids
Reduce BCG dose (1/3). 1 Standard dose most effective. 1/3 dose minimum effective dose. 2 Reduce number of instillations < 3 Reduce dwell time. 3 Use of ofloxacin 6 & 18 hours post first urination following BCG instillation. 4 1.JUrol 2005; 174: 1242-7 2. Eur Urol 2007; 52: 1398-406 3.BJUI 2004; 96: 1290-1293. 4.JUrol 2006; 176:935-9