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Bladder carcinoma
 

Bladder carcinoma

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    Bladder carcinoma Bladder carcinoma Presentation Transcript

    • BLADDER
    • BLADDER CARCINOMA PRESENTED by---Dr.Jyotindra Singh
    • Introduction Most common site of cancer in the urinary tract. 2.7 times more common among men White >black Men-Fourth commonest cause of cancer. Women- Eight most common cause Incidence: 20/100000/year Mortality: 8-9/100000/year Disease of elderly- 67-70 yrs Young patients- better prognosis
    • Estimated new cancer cases. 10 leading sites by gender 38 300 14 900
    • SEMINAR PLAN INTRODUCTION SURGICAL ANATOMY RISK FACTORS PRE NEOPLASTIC / CIS BLADDER MALIGNANCY INVESTIGATIONS/WORK UP CANCER STAGING/MANAGEMENT VARIOUS SURGERIES/ SURGICAL VIDEOS RECENT UPDATES VARIOUS STUDIES/TRIALS
    • Urinary Tract – Urinary Bladder It is positioned immediately superior and posterior to the pubic symphysis. In females, the urinary bladder is in contact with the uterus posterosuperiorly and with the vagina posteroinferiorly. In males, it is in contact with the rectum posterosuperiorly and is immediately superior to the prostate gland. Retroperitoneal organ. When empty - Pyramidal shape. When filled - Oval shape. 1
    • Bladder
    • TRIGONE the Trigone is formed by imaginary lines connecting the two posterior ureteral openings and the anterior urethral opening. The trigone remains immovable as the urinary bladder fills and evacuates. It functions as a funnel to direct urine into the urethra as the bladder wall contracts to evacuate the stored urine. The four tunics that form the wall of the bladder are the mucosa, submucosa, muscularis, and adventitia. 2
    • Bladder- structure of 3 layers – Outer layer Loose connective tissue – Middle layer Smooth muscle and elastic fibres – Inner layer Lined with transitional epithelium
    • Structure of Urinary bladder Serous – formed by peritoneum Muscular- DETRUSOR & TRIGONE Detrusor- External longitudinal layer - Middle circular layer - Internal longitudinal layer Trigone – Detrusor + Ureters Mucosa & Submucosa Urothelium- Multilayered transitional cell epithelium 3-7 layers thick
    • Urothelium Superficial layer- large flat umbrella cells Umbrella cells- binucleated/multinucleated Oval nuclei- perpendicular to basement membrane Cellular polarity exists Basement membrane separate the epithelium from lamina propria
    • 15
    • BLOOD SUPPLY Majorly- Superior & Inferior vesical arteries. Lower part of the bladder- by Obturator,inferior gluteal ,uterine & vaginal arteries. Veins -Vesicoprostatic plexus-Internal iliac veins Lymphatic drainage- External iliac nodes
    • Normal Micturition Motor cortex/frontal lobe centers for micturition Voluntary control Pontine mesencephalic nucleus Sacral spinal cord segments S2, S3, S4 Pelvic nerve Pudendal nerve Bladder
    • RISK FACTORS
    • Risk Factor : Family History Bladder cancer is typically not inherited as a genetic mutation. Reported in association with retinoblastoma & Osteosarcoma ( Chr 13 ) Increase incidence of HLA-B5 & CW4
    • Genetic Abnormalities in chromosome 1,5,7,9,11,17,18&21 have been reported in bladder cancers. A) ONCOGENES Tumor suppressor gene P53 RB gene B) Amplification EGF ERBB2 ERBB1
    • Chemical Exposure  Aniline dyes  2-naphthlamine  4 amino-biphenyl benzidine  common in manufacturing:   petroleum textiles paint  dyes Aromatic amines are slow acetylators
    • Risk Factor : Smoking Smoking is the greatest risk factor- four fold higher. Use of black tobacco Unfiltered cigarettes Both current smoking and a prior history of smoking raise the risk Cessation- 30-60% reduction  Carcinogens in tobacco become concentrated in the urine and eventually damage the bladder lining
    • Miscellaneos Artificial sweeteners Endogenous tryptophan metabolites Analgesic abuse- 5-15 kg for 10 yrs-phenacetin Coffee & tea drinkin Cyclophosphamide – 9 fold risk Immunosupressed patients Balkan Nephropathy Diet rich in Vitamin A & C ,carotene- protective
    • Risk Factor : Urinary Disorders Chronic inflammation of the bladder increases the risk of bladder cancer Irritative effect leads to cell damage  over time Common history includes: repeated urinary tract infection, eg. Cystitis recurrent kidney, ureter or bladder calculi chronic urinary retention requiring catheter (spinal cord injury or neurogenic bladder)
    • Risk Factor : Irradiation Bladder cells are known to be reactive to ionizing radiation  Therapeutic exposure, eg. radiation for cervical, prostate, or rectal cancer  May occur as a result of environmental exposure, eg. nuclear power plant workers
    • Risk Factor : Arsenic Exposure Arsenic is a naturally occurring element found in soil and rocks High levels of arsenic can be found in well water, as well as drinking water near farms and mines  Long-term exposure to arsenic raises the risk of bladder cancer
    • Preneoplastic Abnormalities Atypical Hyperplasia Von Brunn nests Cystitis Cystica Cystitis Grandularis Inverted Papilloma Nephrogenic Adenoma Squamous Metaplasia Vesical leukoplakia
    • Carcinoma In Situ Proliferation confined to epithelium of mucosa. Considerable potential for invasiveness Within 4 yrs- 80% of pts. develop invasive ca Asymptomatic/ Frequency/Urgency/Dysuria Urine cytopathology – Positive in 80-90% cases Cystoscopy- Velvety patch of erythematous mucosa Main site- Verumontanum area Non urothelial mucosa involvement- seminal vesicles,ejaculatory duct, urethral meatus
    • CIS
    • MANAGEMENT- Surgical 1. Asymtomatic FOCAL primary disease – i. removal of carcinogen exposure ii. Intravesical therapy 2. Primary DIFFUSE symptomatic disease without associated bladder tumour i. BCG immunotherapy ii. Early Cystectomy iii. BCG immunotherapy followed by cystectomy
    • Management CIS + concurrent stage Ta or T1 TCC i. TURBT & BCG immunotherapy ii. Early Cystectomy
    • Non Surgical Approach 2. INTRAVESICAL CHEMOTHERAPY i. Thiotepa ii. Doxorubicin iii. Mitomycin C 3. BCG IMMUNOTHERAPY - 6 Week course ( 120 mg of connaught BCG ) - 3 wkly instillation at- 3 months - 6 months - Every 6 months for 3 yrs - 75% patients complete response
    • CLINICAL FEATURES Hematuria Approximately 80% of patients present with gross, painless hematuria. Approximately 20% of patients with bladder cancer present solely with microscopic hematuria. Dysuria and irritative Dysuria and irritative symptoms are present in up to 30% of patients—especially those with carcinoma in situ. Upper urinary tract obstruction Upper urinary tract obstruction is rare on initial presentation and is a sign of advanced disease in 50% of cases.
    • Advanced Malignancy Pain in suprapubic region,buttock,perineum may suggest invasion of paravesical tissue Weight loss Bony pain
    • Pathology of Bladder Cancer 90% Transitional Cell Carcinoma (TCC) 5% squamous cell -more common in middle east – schistosomiasis -also seen in chronic catheterization 0.5%-2% Adenocarcinoma – urachal Rare- Small cell Carcinoma
    • Transitional Cell Carcinoma Accounts for 90-95% of all bladder tumors. Ranges from low grade superficial papillary tumour to high grade invasive disease Histologically – Increased epithelial cell layer -- Papillary folding of mucosa -- Prominent Nuclei -- Clumping of chromatin -- Loss of cell polarity
    • Transitional Cell Carcinoma
    • Cancer- Division Superficial Bladder tumour - not invaded the muscularis Invasive tumour - those that have invaded musclaris propria,perivesical fibroadipose tissue or adjacent structures. Common in trigone,bladder base ,lateral walls 70% papillary,10% nodular,20% mixed
    • Transitional cell carcinoma A: Irregular filling defect represents tumor. B: Enhanced computed tomographic scan of the same patient as in A. Note rim of calcification involving tumor (arrows).
    • Transitional cell carcinoma Unenhanced computed tomogram shows a sessile tumor along the right posterolateral bladder wall. A Foley catheter balloon filled with air is in the center of the bladder.
    • Transitional cell carcinoma A and B: Coronal and axial T1-weighted magnetic resonance images demonstrate invasion of the tumor through the perivesical fat to the pelvic sidewall.
    • TUMOR GRADING DEGREE OF ANAPLASIA PAPILLOMA=GRADE-0 WELL DIFFERENTIATED TUMORS Confined to mucosa=grade 1 Papillary urothelial tumors of low malignant potential (PUTLMP) MOD. DIFFERENTIATED TUMORS=GRADE 2 Low grade urothelial carcinoma POORLY DIFFERENTIATED TUMORS=grade 3 High grade urothelial carcinoma
    • Bladder cancer: Entities 75-85% superficial bladder cancer pTa, pTis, pT1 10-15% muscle-invasive pT2, pT3, pT4 5% metastatic bladder cancer N+, M+
    • Squamous cell carcinoma 5-10 % of bladder tumours Two types- Bilharzial/ Non-bilharzial Bilharzial Bladder Cancer - chronic infection with S. haematobium - exophytic ,nodular fungating lesion - well differentiated - incidence of lymph node,metastasis-low Non Bilharzial SCC - chr. irritation- calculus/ indwelling catheters - keratinized cells- Squamous pearls
    • SCC
    • ADENOCARCINOMA PRIMARY VESICAL ADENOCARCINOMA URACHAL CARCINOMA METASTATIC ADENOCARCINOMA – from rectum,stomach,endometrium,breast,prostrate ovary.
    • AJCC Stage Description Jewett Stage AJCC STAGING Clinical Stage Primary tumor Tx Primary tumor cannot be assessed T0 No evidence of primary tumor Ta Noninvasive papillary carcinoma 0 TIS Carcinoma in situ 0 T1 Tumor invades subepithelial connective tissue A T2a Tumor invades superficial muscle B1 T2b Tumor invades deep muscle B2 T3a Tumor invades perivesical tissue—microscopic only C T3b Tumor invades perivesical tissue—macroscopic C T4a Tumor invades prostate, uterus, vagina C T4b Tumor invades pelvic wall, abdominal wall C N1 Single regional lymph node, <2 cm in diameter D1 N2 One or more lymph nodes, none >5 cm in diameter D1 N3 One or more lymph nodes, >5 cm in diameter D1 Distant metastasis D2 Lymph nodes Metastases M1
    • Stage 0 Bladder Cancer Stage 0a: The cancer is only found on the surface of the inside lining of the bladder, also called noninvasive papillary urothelial carcinoma Stage 0is: The cancer is found only on the inner lining of the bladder, also called flat or carcinoma in situ
    • Stage I Bladder Cancer The cancer has grown through the inner lining of the bladder to the connective tissue layer but has not spread to the thick muscle wall of the bladder
    • Stage II Bladder Cancer The cancer has spread into the thick muscle wall of the bladder (called invasive or muscleinvasive cancer) but not to the fatty tissue surrounding the bladder
    • Stage III Bladder Cancer The cancer has spread to the fatty layer of tissue surrounding the bladder and may have spread to the prostate (men) or the uterus and vagina (women)
    • Stage IV Bladder Cancer The cancer has spread to the pelvic or abdominal wall but not to lymph nodes or other parts of the body, or The cancer has spread to one or more regional lymph nodes but not to other parts of the body, or The cancer has spread to other parts
    • Bladder cancer: Stage and Prognosis Stage TNM 5-y. Survival 0 Ta/Tis NoMo >85% I II T1 T2a-b NoMo NoMo 65-75% 57% III T3a-4a NoMo 31% IV T4b NoMo 24% each T each T N+Mo M+ 14% med. 6-9 Mo
    • SPREAD Direct spread- Local invasion i.Enblock spread- 60% ii. Tentacular invasion- 25% iii. Lateral spread- 10% Metastatic spread Lymphatic spreadpelvic,paravesical,obturator,external iliac nodes Vascular spread- Liver,lung,bone,adrenal Implantation- abdominal wounds,denuded urothelium,resected prostatic fossa,traumatized urethra
    • Adjacent organs involved are prostate(40%),uterus,vagina,ureters,rectum & intestine
    • Diagnosis of Urinary Bladder Cancer Signs and Symptoms Urine Cytological Studies Flow cytometry Diagnostic TUMOUR MARKERS Ultrasonography Diagnostic Imaging – – – – IVP Ultrasound CT MRI Cystoscopy and Biopsy Bimanual Examination Transurethral resection of bladder tumour
    • Modalities for Staging LOCAL EXTENT ( T STAGE ) Excretory Urography Transurethral Ultrasonography Transurethral Resection Select Mucosal Biopsy Cytology Prostate fossa biopsy Examination Under Anaesthesia CT MR
    • Modalities for Staging REGIONAL EXTENT ( N STAGE ) CT MR LYMPHANGIOGRAPHY LAPROSCOPY PET SCANNING
    • SYSTEMIC EXTENT (M STAGE ) Pulmonary - chest film - Linear tomography - CT/PET BONE - Bone scan /Bone survey - MR LIVER - Liver scan - CT/MR/PET - Laproscopy
    • Flow Cytometry Measures DNA content of cells (S-phase cells) It quantitates the aneuploid cell population. If > 15% cells are aneuploid-suggests cancer Diploid tumours- favourable prognosis Triploid /Tetraploid tumours- unfavourable If > 10 % S Phase cells – lymphnode metastasis
    • IMAGING CHEST X-RAY CT is better than chest X-ray ULTRASONOGRAPHY IVU Upper urinary tract Filling defect Irregularity
    • Ultrasonography of Bladder Ca
    • IVU of Bladder Tumor
    • CT SCAN Staging of the tumour Extent of primary tumour Rule out invasive bladder cancer Assess pelvic LN status ( > 1 cm ) Visceral metastasis Evaluation of upper urinary tract
    • CT scan of bladder Ca
    • IMAGING MRI Staging ,better than CT PET scan Metastatic workup LAPROSCOPIC STAGING Port site recurrence BONE SCAN –not much role
    • CYSTOURETHROSCOPY MOST IMP. BIOPSY
    • Bladder Ca under cystoscopy
    • Complications and Sequela of Cystoscope Profuse bleeding. Damaged urethra. Perforated bladder. Urinary tract infection. Injured penis. scar tissue.
    • BIMANUAL EXAMINATION Under GA with full relaxation Performed prior to tumour resection and then again after endoscopic resection Superficial tumour- Disappearance of mass Invasive tumour -Fixed/Indurated or mass persists after resection
    • Bladder cancer: Management Carcinoma In Situ 75-85% superficial bladder cancer pTa, pTis, pT1 10-15% muscle-invasive bladder cancer pT2, pT3, pT4 5% metastatic bladder cancer N+, M+
    • ENDOSCOPIC SURGERIES VIDEO ASSISTED TURBT Under GA/Regional Remove all visible tumors Bimanual examination must before and after Ideal Method – 2 specimen to be collected First superficial portion of the tumour Deep portion along with underlying bladder muscle The base of resection site is fulgrated
    • ENDOSCOPIC SURGERIES
    • ENDOSCOPIC SURGERIES
    • TUR of Bladder Tumor (TURBT)
    • After TUR
    • ENDOSCOPIC SURGERIES
    • ENDOSCOPIC SURGERIES COMPLICATIONS Irritation and minor bleeding Uncontrolled haematuria Perforation REPEAT TURBT Incomplete removal T1 tumor Second opinion ROLE OF ADDITIONAL BIOPSIES All suspicious lesions Not required for low risk groups
    • BCG Therapy Wait for 2 weeks after tumour resection Early administration- risk of severe complication Commonest side effect- Bladder irritability Due to immune stimulation & inflammatory reaction. No direct toxic effect on malignant cells Stimulates a generalized immune response – result in tumour destruction
    • IMMUNOTHERAPY BCG VACCINE 6wk induction course (weekly) 6wk gap 3wk instillation at 3rd and 6th month Then every 6months for 3 years Don’t give more than 6wks in single sitting Avoid quinolones
    • IMMUNOTHERAPY BCG VACCINE Contraindications Immunocompromised Immediately after TURBT Allergic Gross haematuria Traumatic catheterization Total incontinence
    • ELIMINATION OF RECURRENCE after prophylaxis EXISTING DISEASE BCG ERADICATION OF CIS 20 60 72 Mitomycin-C 30 50 40 Doxorubicin 40 30 25 Thiotepa 45 35 15
    • Fever<38.5 Fever > 38.5 Allergic reaction 12- 24 HRS NO Rx Isoniazid 300 mg daily for 3 months Acute severe SEPSIS iIlness Isoniazid 300 mg daily for 3 months Isoniazid 300 mg Isoniazid 300 mg Rifampicin 600 mg Rifampicin 600 mg Hold BCG until symptoms have resolved May resume BCG when asymtomatic Further BCG is indicated only if benefit excess risk Ethambutol 1200 mg daily for 3 months no further BCG Ethambutol 1200 mg Cycloserine 500 mg Twice daily To consider prednisolone 40 mg iv acutely
    • IMMUNOTHERAPY INTERFERONS Expensive Less effective With BCG Decreases side effect Decreases dose of BCG OTHERS Key hole limpet hemocyanin (KLH)- Copper containing antigenic protein.
    • LASER THERAPY ARGON LASER- 1 mm penetration Nd:YAG laser – 4-5 mm penetration Used to treat the tumour bed following TUR Newer KTP LASER- Safer ( 4-5 mm ) Indication- Small,superficial,recurrent lesion Tumour larger 2.5 cm not available. Drawback- tumour tissue not available
    • PERIOPERATIVE INTRAVESICAL CT MMC(MITOMYCIN-C) Administer within <6hr Retain solution for 1hr Reduces recurrences about 50% Single dose Through 3 way catheter No role after 24 hr With held CT if extensive resection BCG contraindicated (sepsis + death)
    • ADJUVANT CT MMC DOXORUBICIN THIOTEPA GEMCITABINE TAXANES PACILITAXEL COMBINATION THERAPY
    • Photodynamic Therapy Combines non toxic photo sensitivity dyes + Visible light to destroy cancer cells. Indication- CIS, Ta, T 1 tumour Photofrin-II – 2 mg/kg body weight is given After 48 hrs –bladder illuminated with red light (630 mm) Cascade of photo chemical reaction- generate cytotoxic molecular oxygen.
    • Indications for Cystectomy Persistent carcinoma in situ Recurrence with invasion of the lamina propria Persistent involvement of the prostate by TCC Invasion of the muscularis propria Rarely contracture and incontinence resulting from intravesical therapy
    • Invasive Bladder Cancer Diagnosis of muscle invasion (T2 – T3 ) established Metastatic disease should be excluded Aggressive therapy- Bladder preservation - Bladder reconstruction Radical cystectomy- gold standard TUR- small tumors with superficial muscle invasion
    • Segmental cystectomy Tumour > 2 cm from bladder neck No evidence of CIS Tumors in vesical diverticulum Tumours arising from urachus. Complications- implantation of tumour cells in surgical wound - Recurrence – upto 70 %
    • RADICAL CYSTOPROSTATECTOMY Radical cystoprostatectomy in male and anterior exenteration In female coupled with en bloc pelvic lymphadenectomy ,remain the standard surgical treatment in the absence of metastatic disease.
    • Radical Cystectomy INDICATIONS Primary adenocarcinomas Squamous cell carcinoma with or without schistosomasis Sarcoma of the bladder Carcinoma in situ Superficial papillary carcinoma Invasive carcinoma
    • RADICAL CYSTOPROSTATECTOMY STRUCTURES REMOVED MALE Bladder Peritoneal attachments Prostate Seminal vesicle B/L pelvic lymphadenectomy IN WOMEN Cervix ,uterus, ant.vaginal vault, urethra should be included
    • RADICAL CYSTOPROSTATECTOMY Analysis of the urethral margin at the time of cystectomy before urinary tract reconstruction is standard practice MALE URETHRA Prostatic urethra involvement –do simultaneous or delayed urethrectomy . Pt considered for orthotopic reconstruction should be cautioned about its use till histological report. FEMALE URETHRA Better do enbloc urethrectomy
    • Urinary diversion: Ileal Conduit Urine empties through stoma No reservoir therefore incontinent Nursing: teach – Appliance application – Skin care
    • Urinary Diversion: Ureterostomy Ureterostomy – Divert urine directly to skin opening – Must wear bag or pouch after surgery – Nursing: Skin care Bag placement
    • Urinary diversion: Ileal reservoir Kock’s pouch Reservoir created from ascending colon and terminal ileus No appliance needed Nursing: – teach selfcatheterizations – Skin care
    • LYMPHADENCTOMY Pelvic lymphadenectomy provides insight into the local extent of disease. Extended lymph node dissection should include the distal para-aortic and paracaval lymph nodes as well as the presacral nodes Lymph nodes positive disease Concept of ratio based lymph node staging or lymph node density have have great prognostic value
    • RADIOTHERAPY EXTERNAL BEAM RADIO THERAPY No randomized trail to compare with surgery 5000-7000cGy 5to 7 weeks Local recurrence common Only pt who are surgically not fit Hyperfractionation is a future hope PRE OP RT Local control in T3 Survival advantage not demonstrated
    • CHEMOTHERAPY NEOADJUVANT Down staging Inoperable Rx of micrometastasis Improved survival. PERIOPERATIVE No survival benefit ADJUVANT Some studies showed increased survival.
    • Chemotherapy for bladder cancer Bladder cancer is a chemosensitive disease Active single agents. RR –Cisplatin –Carboplatin –Gemcitabine –Ifosfamide 30% 20% 20-30% 20%
    • Chemotherapy for bladder cancer Combination chemotherapy. RR – MVAC 10-25% – Gemzar / Cisplatin 40-50% – Gemzar / Carboplatin – Taxol / Carboplatin 65% 40-60%
    • Combined Radio- and Chemotherapy CR 5y.OS Radiotherapy 57% 47% RT and cisplatin 85% 69% RT and carboplatin 70% 57%
    • CHEMOTHERAPY COMMON REGIMENS CISCA CMV MVAC/MVEC (commonly used)
    • ALTERNATIVE Rx RT TUR+PARTIAL CYSTECTOMY TUR+PARTIAL CYSTECTOMY+CT BLADDER PRESERVATION PROTOCOL INTERSTITIAL RT INTRA ARTERIAL RT HYPERTHERMIA AND CT
    • Bladder-sparing protocol Transurthral resection Induction Therapy: Radiation + chemotherapy (cisplatin, paclitacel) Cystoscopy after 1 month no tumor Consolidation: RT + CT tumor cystectomy
    • Metastatic bladder cancer 50 % patients with high grade cancer die of disseminated disease within 2 yrs of presentation. Palliative Radiation therapy – 3000 to 35OOcGY given in ten fractions Intravesical alum (1 %) formalin (1-10%) instillation:to control haemorrhage from advanced bladder tumor or radiation cystitis.
    • CHEMOTHERAPY FOUR – DRUG COMBINATION M-VAC Methotrexate 30 mg/sq.m – 1,15 & 22 Vinblastine 3 mg/sq.m- 2,15 & 22 Adriamycin 30 mg/sq.m on day 2 Cisplatin 70 mg/sq.m on day 2 Repeat cycle every 28 days ,totally 6 cycles
    • RECENT UPDATES/CHANGING APPROACH
    • MINIMALLY INVASIVE OPEN ROBOTIC CYSTECTOMY
    • Role of MR Virtual Cystoscopy in the Detection of Urinary Bladder Neoplasms
    • Steps for Creating Virtual Cystoscopy Patient preparation and Image acquisition Image processing Segmentation. Fly through (creating virtual reality) Image analysis Image display
    • Combined virtual and axial MR images for detection of bladder lesions. Sensitivity Specificity lesions less than 1 cm 90.3% 100% lesions 1 cm or more 100 % 100 % Overall lesions 96.9% 100 %
    • Female patient, 45 years old , presenting by hematuria and frequency.
    • Male patient, 65 years hematuria and dysuria. old, presenting by
    • Male patient, 74 years old, hematuria and frequency. presenting by
    • The Advantages of Virtual Cystoscopy versus Conventional Cystoscopy Non-invasive technique. No anesthesia . Accurate localization of a lesion . Accurate measurement of tumor size. Data of large number images in one image. More than view . Access to the anterior bladder wall or the lumen of a diverticulum . Detect lower ureteric extension. MR images assess extravesical extension.
    • Potential Diagnostic Markers S phase (Ki67) P53 P21 – downstream of p53 – if + favorable outcome Rb
    • Androgen Receptor Expression in Bladder Cancer NON-TUMOR NON-TUMOR TUMOR A A B pTa pT1 pTa NT C C D pT2 E NT pT3 F
    • Some ―new‖ ones NMP22 dipstick (BladderChek™) FISH (Urovysion™) Immunocyt™
    • NMP22 Antigen Malignant urothelial cells contain up to 80 times higher concentration of NMP22 antigen than normal urothelial cells and release it upon cell death. Based on previous studies, an NMP22 test result > 10 U/ml in the urine is associated with a high probability of bladder cancer
    • Created to identify urine with NMP22 antigen  10 U / mL – Requires 4 drops of freshly voided urine – results available in 30 minutes – Positive result if NMP22 antigen level  10 U / mL
    • Molecular Progression of Bladder Cancer 9q- Precursor lesion 14q- Papillary hyperplasia Papillary cancer 17p- (p53) 9p-(p16) 11pInvasive Cancer 13q-(Rb) Dysplasia CIS
    • Molecular Detection
    • Microsatellite Analysis 32-P Isotopic technique Fluorescent technique
    • Intracavitary Hyperthermic Perfusion-Chemotherapy (ICHP)
    • Methods of Intracavitary Hyperthermic Perfusion ChTx Intraperitoneal (IPHC) Intrapleural (IPlHC) • Peritoneal Carcinomatosis • Malignant Ascites • Pseudomyxoma peritonei • i.p. disseminated Mesothelioma • Neoadjuvant, Salvage & Consolidation Therapy • Adjuvant (?) • Malignant Pleural Effusion • Pleural Carcinosis • Malignant Pleuramesothelioma Intravesicular (IVHC) edh ICHS Shenzhen 2004 • Recurrent Urothelial Carcinoma
    • Peri-/postoperative I.P. Chemotherapy Preoperative (before surgery) Perioperative Intraoperative (during surgery) Postoperative (early) edh ICHS Shenzhen 2004
    • Percutaneous Intraperitoneal Hyperthermic Chemoperfusion - edh ICHS Shenzhen 2004
    • IVHC with Microwaves Radiativ (intravesicular microwave antennae,
    • Bladder Cancer – IVHC
    • Bladder Cancer – PR/SD edh ICHS Shenzhen 2004
    • Summary & Conclusion Long-term, percutaneous or intravesicular hyperthermic perfusion-chemotherapy is one of the most powerful new treatments in oncology It is feaseable and has minimal side effects compared to standard chemotherapy It can be repeated oftenly (> 30 Tx)
    • PREVENTION Vitamins-A,B6,C,E. Polyamine synthetic inhibitors Deitary factors Acidification of urine Avoid high fat /cholestrol diet Green tea consumption decreases chances Take more fluids Cox -2 inhibitor (celecoxib) decreases
    • SUMMARY Bladder CA is not rare Incidence is increasing in both sexes Chemical carcinogens have big role Late presentation in developing world Lack of awareness in early diagnosis Urine cytology and cystoscopy are good screening Grade is most important for prognosis Stage before and after endoscopic surgeries Bimanual examination has big role
    • SUMMARY Endoscopic surgeries and immunotherapy are main stay in non- muscle invasive tumors Surgery is main stay of Rx in muscle invasive tumors RT is equally challenging Neoadjuvant Rx has proven role in increasing survival Newer modalities of treatment are under investigational
    • REFERENCES Short text book of BAILEY & LOVE McGregor Synopsis of surgical anatomy Cambells Urology Genitourinary cancer surgery by Crawford CANCER PRINCIPLES- De Vita Chemotherapy of urogenital tumours-Murphy Bladder Cancer:Principles of combination therapy Urologics clinics of North America RECENT ADVANCES- WOLTERS KLUWER RECENT ADVANCES- RSG
    • HELLO– ANY QUESTIONS
    • Thank you Have A Great Day…