HEMATURIA andCarcinoma Urinary Bladder

Learning Objectives

to enumerate causes of hematuria To enlist positive features on elaborate history

and relevant clinical examination in a case of hematuria and of a bladder tumour

able to suggest and interpret relevant investigations in a case of hematuria and of a bladder tumour

to give justification for and against a diagnosis Classify bladder tumours Enlist steps in management of hematuria & TCC Enlist differents roles an internist has to play in

TCC

Bladder tumours

Primary Urothelial, 95% Con tissue

Angioma, fibroma, myoma, sarcoma Extra adrenal pheochromocytoma

Secondary Sigmoid, rectum, prost, uterus, ovary,

bronchus

Types

Benign papillary tomours Simple frond with villi on vascular core Sea anemone

Inverted papiloma Proliferation under normal mucosa ( covered)

Carcinomas TCC, (mix, metaplasia in TCC) 90 % Squmous cell (bilharzia, stone irritation) 5% Adenocarcinoma, ( urachal remnents, fundus)

2%

Urothelial tumours

TCC Risk factors

Smoking 40% Occupation /exposure to chemicals

Oncogenes ras, c-erb B 1 & 2, E2F3 Suppersor p53, p21, p16, retinoblastoma

genes mettaloproteinases

Clinical features

Hematuria, may not be reported Clot retention LUTS Dysurea ( malignant cystitis)

Pain Pelvic, suprapubic, genital, thigh Advance malignancy, nerve involvement Loin– pyelonephritis, ureteric

obs/hydronephrosis

Hematuria

Gross blood in urine Microscopic 3 to 5 RBCs per HPF Always abnormal =

whether macro, micro, single episode or patient on anticoagulants

3 glass test

Terminal : proximal urethra, baldder neck/trigone,

Initial: distal to ext sphincter,

total : baldder / upper tract

Bleed per urethra

History & exam not sufficent to make diagnosis, so always needs investigations.

Degree bears no relation with severity of disease.

Always take it serious until proved otherwise

Cause may be any where in urinary tract Kidneys ----- Surgical Causes

Congenital – polycystic, PUJ, medullary sponge kidney

Trauma – stone, rupture, runner’s hematuria Inflammation – Nonspecific, TB, Neoplastic – RCC, TCC pelvis, Wilm’s papillary necrosis Vascular / Congestion – AV malformations, RHF,renal

vein thrombosis, Infarction – arterial thrombosis / embolism Medical causes Glomerular disorders – glomerulonephritis, IgA

nephropathy, Benign idiopathic hematuria Lymphoma, multiple myeloma, amiloidosiss

Surgical Causes

Ureters Stones, TCC ureter, VUR, stricture,

Bladder Trauma, stone, catheter trauma Inflammation – cystitis, TB, Bilharzia,

post-radiation cystitis, cyclophosphamide chemo.

Neoplastic – TCC, adeno squaamous Prostate

BPH, CaP, prostititis,

Surgical Causes

Urethra Trauma, rupture, stone, catheter trauma Inflmmation – urethritis Neoplaastic – TCC urethra, penile Ca Atrophic urethritis

Surgical Causes

Miscellaneous Endometriosis Diverticulitis Appendicitis Abdominal aortic aneurysm Foreign body

Surgical Causes

False hematuria food colors / drugs staining red (beet roots, Dindevan, pyridium,furadantin, rifampicin,= differentiation made with microscopy (RBCs)

False +ve dipstick test. hemoblobin, erthrocytes, myoblobin, pigmenturia. DD= microscopy

Factitious = source outside urinary system Vaginal bleeding, malingering

Medical Causes, cause of hematuria may not be in urinary tract but outside it

Systemic disorders Haematological

Bleeding disorders purpura, sickle cell disease, hemophilia, scurvy

therapeutic anticoagulants, Miscellaneous

Malaria, SLE, Henoch Schonlein purpura, hypersensitivity angiitis, bacterial endocarditis, Wegener’s granulomatosis, Good pastures Syndrome

Points in history

Pain – renal, ureteric stone, clot, cysts, hydronephrosis, adv. Tumors, trauma

Trauma, wt. loss, LUTS, dysuria, fever, riger, constitutional symptoms

Pattern of hematuria- gross, micro, partial, total, persistant/continuous, intermittent,

Clots long threadlike, amorphous, fresh, old Smoking, occupaton, travel to schist areas, Rash, joint pain (SLE) URTI-PSGN Purpura, rash, echymosis, easy bruiseability, bleed

from multiple sites Medication – color, anticoagulants Exercise, sepsis, systemic diseases = liver, renal failue Mass, TB

Management Steps

History Presenting complaints with details Direct questions regarding other urinary

symptoms Differential Diagnosis

Direct questions regarding stage of disease

Direct questions regarding systemic illnesses.

Direct questions regarding risk factors

Management Steps

Examination Appearance Vitals GPE Systemic exam

Abdomen ----- DRE Chest

Clinical examination

No physical sign / Anything could be found Disoriented – liver / renal failue Catheter / irrigation / drip / canulla Pain agony – stone, HN, retention Cechhexia, Pulse shock, sepsis BP , normal, shock, high ( HTN, renal failure) Temp infection Resp renal failure, acidosis Purpura, rash, echymosis Pallor / degree, anemia hematuria, renal failure Jaundice, edema, L.nodes Palpable visreras, L,S,K,K,UB,LN, masses, prostate, urethra, testes, epid- vas (TB),

meatus,stricure, retention

Workup

Esteblish hematuria - dipstick

Urine RE/microsscopy-RBCs

Urine CS – infection, doesn’t rule out other causes

flow cytometery

Urinary cytology May be helpful, being noninvasive, but

not established to a point to replace routine workup.

tumour markers-NMP22, BTA Yield varies from study to study &

grade and type lesion

Management Steps

Investigations Base line

urea creatinine Hb

Specific IVU ? Contrast CT Scan/ MRI, local & nodal staging Ultrasound Sophisticated tests timour markers

cystoscopy

Advantages of US

cheap, easy, easily available, noninvasive,

no countraindication, nontoxic, no side eff/reaction

Disadvantages US

good for renal parenchyma but not for pelvicaliceal system and ureter

not very good for bladder, small lesions-miss

Observer dependant, inter and intraobserver variability

Imaging: US findings Kidney: size, echogenicity, cortical

thickness, cysts, mass, hydronephrosis, stone, C/m ratio

Ureter: dilated, stonne, mass, ureterocele

Bladder: stone, wall thickness / smooth, mass, clot, diverticula, capacity, pre- and postvoid volume

Prostste size, echogenicity

IVU

Conventional, NOW CONTROVERTIAL Invasive IV contrast, side eff/ adverse eff – anaphylaxis, toxicity,- drug, radiation)

Very good for pelvicaliceal system and ureter

May not be diagnostic Many would proceed to cystoscopy after USG

leaving IVU

IVU

Demonstrates anatomy –normal / cong

abormalities function

secretion thru kidney, transport thru collecting system, storage in bladder and

evacuation.

IVU

Principle Indications

Stone, hematuria, trauma, congenital abnormalities, mass, assessment of function, obstruction

Preparation Purgation, hydration

Precautions Not during pain, renal status, hydration, clear KUB, allergy

Procedure Test dose, procedure – timings

Side / adverse reactions – management of Contra-indications Interpretation Disadvantages Constrast and other things required

radiation

IVU Findings

Faint mass shadow on plain film,

ROS, Hydronephrosis Wall smoothness filling defect,

mass shadow, Radiolucent stone clot, fungus, FB

Management Steps

Prepare for surgery / aneasthesia

Fitness Co-morbidities ( smoking = IHD, COPD)

Hb. Transfusions

Cloting profile

Cysto-urethro-scopy Visualizes lower tract starting at ext

meatus, leading to bladder.( U, P, BN, ) bladder

capacity, bleeding site, edema/ congestion,ulcer, mass, granuloma, orifices, diverticula, trabeculations, stone,

Biopsy, brushings cytology, Retrograde uro/pyelography / uretero-

renoscopy USG+cystoscopy +/_ RPG may obviate

need for IVU in most but not all cases, in which case a formal IVU or a constrast CT scan is required

Management Steps

EUA, Bimanual examination Cystoscopy, Flexible / Rigid

Inspection Resection, as complete as possible

Superficial biopsy A Deep / base biopsy B Random mucosal biopsies C irrigation

Bimanual examination

Management Steps

Histopathology report should include Type of lesion Type of tumour Grade of tumour (degree of

differentiation) Muscle included / involved

Superficial disease ========= 85% Invasive disease ========= 15%

Random mucosal biopsies ? CIS

Open excision or biopsy

Avoided Up-staging Radiation cauterize

Management Steps

? Further staging Superficial disease not required Invasive disease / CIS

Bone scan CXR LFTs / ultrasound Ct scan abdomen pelvis with double contrast

/ MRI Local invasion, liver, lymph nodes

3 biological behaviral pattrens

Non-muscle invasive (superficial) disease

Muscle invasive disease

Flat noninvasive CIS(primary CIS)

pTa, pT1 pT2+ CIS

70% new cases 25% 5%

Good prognosis Bad, 5 yr survival 50%

Poor unless treated early

Recur 70%, invade 15%

Invade, metastasize Invade, metastasize

Exophytic, papillarySingle, multiple

Solid, large,1 or moreIrregular, ulcerated

Flat, velvety mucosa, angry looking vessels

Pedunculated (stalk) Broad base

Field change +/_ (con CIS)

Lamina propria muscularis Intra epithelial

Comptete resection Persist on Bim Exam

Met death 30-50% 50% deaths mets

Down stage/salvage cyst

Endoscopic + intravesical

Primary surgical treatme

Endo+intrrav+/-surgry

Stage wise treatment Stage Description Traetment

Tis Ca insitu Complete TURBTIntravesical BCG-> repeat-> RC*

Ta Single, low to moderate grade, not recurent

Complete TUR alone

Ta Large, multiple, high grade, recurrent

Complete TUR intravesical chemo- or immunotherapy

T1 Complete TUR-> intravesical chemo- or immunotherapy

T1G3 Complete TUR ->Intavesical BCG

-> repeat ->radical cystectomy

T2 Radical Cystectomy (RC) *

T2-4 RC, Radiation , •Neoadj Radiation -> RC ( salvage)•Neoadj chemo -> RC•RC -> adj chemo•Combined chemo-radio

Any T, N+, M+

•Systemic chemo followed by selective surgery or irrediation

Metastatic disease

Systemic Chemotherapy Radiotherapy Combined chemo-radio

Intravesical Chemo- or Immunotherapy Mytomycin C Thiotepa Doxyrubicin BCG Newer agents

Alpha interferon bropiramine

Systemic Chemotherapy

MVAC (methotraxate, vinblastine, doxyrubicin,

Cisplatin) CMV

(Cisplatin, methotraxate, vinblastine) CISCA

(Cisplatin, doxyrubicin, cyclophosphamide)

New Systemic Chemotherapy Gemcitabine Paclitaxel ifosfamide

Radical Cystectomy

pT2-3, M0N0, CIS Incision Pelvic

Lymphadenectomy Frozen sections Organs Urethractomy diversion

diversions

Incontenant reservoirs Ileal condouit

Contenant reservoirs Ureterosigmoidostomy Orthotopic neobladder Catheterizable stoma pouches

Metrofenof ‘s Indiana struder

Open Procdures / Biopsy

Should never be performed Cauterize Radiotherapy

Radiation

External beam Radiation 5000 –7000 cGy 5 –8 weeks

Local Beads / wires

Management of associated problems Pain Bleed renal failure others

Follow Up

Cystoscopy 3 monthly for 2 years 6 monthly for 3years Yearly upto 10 years Recurrence ===== new cycle

IVU yearly for upper tract

Prognosis

Treatment option wise prognosis

Resident’s Role History & Exam & Investigations Identify active problems n treat

Retention ------ catheter Clots ------- bladder wash , 3 ways foley and

irregation Persistant hematutia ------- ‘alam‘ washes Systemic illnesses medical conslt Metastatic disease problems oncologist

conslt Transfusions donor orgs Fitness for aneasthesia Surgical items donor orgs Pre- and postop care Bowl preparation Stoma counsilling and care Counselling and moral build up Coordination with different consultants

remember

Hematuria, many causes, always abnormal

Antibiotic, not sole treatment of Ultrasound, not good in IVU / cystoscopy, essential in Histopath, details are imp Followup, key to avoid recurence

Hematuria of obscure origin 20% Just explain that investigations that are

usually carried oout have not demonstrated any cause -

Do reassure but Never explain that all is OK, a future investigation may show some cause in evolution or appearing then

Follow up is required Emmergency cystoscope in cases of

active rebleed