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Bladder Cancer
Aslı Deniz Yerlikaya
Deniz Denizci
Hazal Ekşi
Anatomy:
The wall of the bladder has 4 main layers.
•
The innermost lining is called the
urothelium or transitional epithelium.
•
Beneath the urothelium is a thin layer of
connective tissue, blood vessels, and
nerves.
•
Next is a thick layer of muscle.
•
Outside of this muscle, a layer of fatty
connective tissue separates the bladder
from other nearby organs.
EPIDEMIOLOGY
• Second most frequent cancer of genitourinary tract
(worldwide).
• Most frequent cancer of genitourinary tract in Turkey.
• Second most frequent cancer in Turkey.
• White men face a lifetime risk of almost 3%; white women
and black men face a risk of about 1%, and black
women, about 0.5%.
• The most common type is transitional cell carcinoma (other types
include squamous cell carcinoma and adenocarcinomas).
• The male:female ratio for bladder cancer is 4:1(poorer prognosis in
female patients)
• Incidance increases with age (average age at diagnosis: 65-70)
• Early treatment significantly decreases mortality in invasive
disease.
Etiology
• Cigarette smoking
(alpha and beta naphtilamine =arylamines)
• Chemical Carcinogens
• Cyclophosphamide (acrolein)
• Pelvic radiation therapy (2-4 x high)
• Irritation / inflamation of the bladder
• Genetic predispositon
• Diet (artificial sweeteners-cyclamate,saccharin)
Pathogenesis and Pathology
• Bladder cancer is often described as a polyclonal field change
defect with frequent recurrences due to a heightened potential
for malignant transformation. However, bladder cancer has also
been described as resulting from implantation of malignant cells
that have migrated from a previously affected site. The latter
occurs less often and may account for only a small percentage
of cases
Invasive versus non-invasive bladder cancer
Bladder cancers are often described based on how far they have invaded into the wall of the bladder:
• Non-invasive cancers are still in the inner layer of cells (thae transitional epithelium) but have not
grown into the deeper layers.
• Invasive cancers have grown into deeper layers of the bladder wall. These cancers are more likely to
spread and are harder to treat.
A bladder cancer can also be described as superficial or non-muscle invasive. These terms include
both non-invasive tumors as well as any invasive tumors that have not grown into the main muscle
layer of the bladde
Papillary versus flat cancer
Bladder cancers are also divided into 2 subtypes, papillary and flat, based on how they grow
• Papillary carcinomas grow in slender, finger-like projections from the inner surface of the bladder toward the hollow
center. Papillary tumors often grow toward the center of the bladder without growing into the deeper bladder layers. These
tumors are called non- invasive papillary cancers. Very low-grade (slow growing), non-invasive papillary cancer is
sometimes called papillary urothelial neoplasm of low-malignant potential (PUNLMP) and tends to have a very good
outcome.
• Flat carcinomas do not grow toward the hollow part of the bladder at all. If a flat tumor is only in the inner layer of
bladder cells, it is known as a non-invasive flat carcinoma or a flat carcinoma in situ (CIS).
If either a papillary or flat tumor grows into deeper layers of the bladder, it is called an invasive urothelial (or transitional
cell) carcinoma.
• Most bladder cancers start in the innermost lining of the bladder, which is
called the urothelium or transitional epithelium. As the cancer grows into
or through the other layers in the bladder wall, it becomes more advanced
and can be harder to treat.
• Over time, the cancer might grow outside the bladder and into nearby
structures. It might spread to nearby lymph nodes, or to other parts of the
body. (If bladder cancer spreads, it often goes first to distant lymph nodes,
the bones, the lungs, or the liver.)
Transitional Cell Carcinoma
• These cancers start in the urothelial cells that line the inside of the bladder.
• It arises from stem cells that are adjacent to the basement membrane of the
epithelial surface. Depending on the genetic alterations that occur, these cells
may follow different pathways in the expression of their phenotype
• The most common molecular biologic pathway for TCCs involves the
development of a papillary tumor that projects into the bladder lumen and, if
untreated, eventually penetrates the basement membrane, invades the lamina
propria, and then continues into the bladder muscle, where it can metastasize.
Nearly 90% of transitional cell bladder tumors exhibit this type of behavior
• The remaining 10% of TCCs follow a different molecular pathway and are
called CIS. This is a flat, noninvasive, high-grade urothelial carcinoma
tumor that spreads along the surface of the bladder and, over time, may
progress to an invasive form of cancer that behaves the same as invasive
TCC.
Squamous Cell Carcinoma
• SCC of the urinary bladder is a malignant neoplasm that is derived from
bladder urothelium and has a pure squamous phenotype
• In the United States, only about 1% to 2% of bladder cancers are
squamous cell carcinomas
• Reportedly, SCC has less of a tendency for nodal and vascular distant
metastases than does urothelial carcinoma
Adenocarcinoma
• Adenocarcinomas account for less than 2% of primary bladder tumors.
These lesions are observed most commonly in exstrophic bladders and
are often associated with malignant degeneration of a persistent urachal
remnant
Small cell carcinoma
• Small cell carcinoma of the urinary bladder is a poorly
differentiated, malignant neoplasm that originates from
urothelial stem cells and has variable expression of
neuroendocrine markers. Morphologically, it shares features
of small cell carcinoma of other organs, including the lung
Other rare forms
• Other rare forms of bladder cancer include leiomyosarcoma,
rhabdosarcoma, carcinosarcoma, lymphoma, and small cell carcinoma.
• Leiomyosarcoma is the most common sarcoma of the
bladder.Rhabdomyosarcomas most commonly occur in children.
Carcinosarcomas are highly malignant tumors that contain a combination
of mesenchymal and epithelial elements.
• Primary bladder lymphomas arise in the submucosa of the bladder.
Except for lymphomas, all these rare bladder cancers carry a poor
prognosis.
Signs and Symptoms
• People with bladder cancer may experience the following symptoms or
signs. Sometimes, people with bladder cancer do not show any of these
symptoms. Or, these symptoms may be caused by a medical condition
that is not cancer
• Painless gross hematuria-approximately %80-90 of patients with
bladder cancer present with painless gross hematuria
• Irritative bladder symptoms(dysuria,urgency,fequency of urination)
• Pelvic or bony pain ,lower extremity edema,or flank pain-in patients
with advanced disease
• Palpable mass on physical examination-rare in superficial cancer
Dıagnosıs
Blood culture
• CBC
• (elevation of SGOT, SGPT , azotemia) anemia symptoms
Physical examination
• palpable mass
• do general phsysical examination for methastasis
Urinalysis and Urine Culture
• Urinalysis is used routinely to evaluate for the presence of red blood cells (RBCs),
WBCs, and protein and to assess for urinary tract infection.
• Gross hematuria always requires a careful assessment with imaging studies of
the entire urinary tract (CT urography) and cystoscopy.
Urine Cytology
• Voided urine cytology is the standard noninvasive method for
diagnosis in the detection of bladder carcinoma.
• Cytology is used to assess morphologic changes in intact
cells.Unfortunately, the sensitivity of cytology is low, with various
studies reporting values between 11% and 76%.
• Sensitivity depends largely on the degree of tumor differentiation.
High-grade tumors with marked pleomorphism and distinctly
abnormal nuclear features are identified more accurately.
Intravenous Pyelography
• IVP is the traditional standard for upper tract urothelium imaging; however, it is a
poor modality for evaluating the renal parenchyma.
Renal Ultrasonography
• Ultrasonography is also commonly used in the diagnosis of bladder cancer.
However, urothelial tumors of the upper tract and small stones are easily missed.
use in patient with hematuria
Biomarkers
• Over 30 urinary biomarkers have been reported for use in bladder cancer
diagnosis, but only a few are commercially available. The 2011 EAU
guidelines on non–muscle-invasive bladder cancer state that cystoscopy
should be performed in all patients with symptoms of possible bladder
cancer and that no noninvasive test can take its place.
• BTA,NMP-22,Hyaluronic acid,activity of hyaluronidase nz
Computed Tomography Scanning , MR, PET
• Upper tract imaging is necessary for the hematuria workup.
• The imaging modality chosen should be able to visualize the kidneys and the urothelium.
Cystoscopy
• Cystoscopy is the primary
modality for the diagnosis of
bladder carcinoma because of
its low risk and because biopsy
specimens can be taken and
papillary tumors resected during
a single procedure.
• standart olarak beyaz ışıkla
yapılır ancak carsınoma in situ
için 5-ALA ve HAL ile boyanarak
flourasant ışığı ile bakılır.
Differential diagnosis
• Cystitis in Females
• Hemorrhagic Cystitis: Noninfectious
• Nephrolithiasis
• Renal Cell Carcinoma
• Renal Transitional Cell Carcinoma
• Ureteral Trauma
• Urinary Tract Infection in Males
Staging
STAGING — Stage is the most important independent prognostic variable for
progression and overall survival for invasive bladder cancer. Comprehensive
pathologic staging requires cystectomy (with lymphadenectomy). However, clinical
staging can be applied for those patients who will undergo neoadjuvant therapy.
For patients with non-muscle invasive cancer (Ta, T1, Tis), stage is determined by
transurethral resection of bladder tumor (TURBT) and bladder biopsies.
Clinical staging — Clinical staging is based on information derived from bimanual
exam and imaging studies as well as pathology results from the cystoscopic
biopsy or TURBT. However, the initial pathology obtained from cystoscopy
specimens does not always accurately reflect the pathologic stage based on
radical cystectomy.
Pathologic staging — The standard staging system is the Tumor, Node,
Metastasis (TNM) system, which is based upon pathologic studies of cystectomy
specimens This staging system is applied to urothelial carcinoma, squamous cell
carcinoma, undifferentiated carcinoma, and adenocarcinoma arising in the
bladder.
Treatment
• klinik evreye göre üç şekilde olur:
• non musccle invasive
• musscle invasive
• metastatic
TUR ( Transurethral Resection of the Bladder)
• first treatmment aproach
• hıstopathologic evaluatiıon an d staging in every tumor
• used as a treatment in superficial tumors
Treatment of Non–Muscle-Invasive Disease (Ta, T1, CIS)
1.low risk:unifokal Ta G1 3cm >
2 High:T1 G3 multifocal / recurren Cis
3.moderate:multıfokal 3 cm< the other tumors
Immunotherapy and chemotherapy
• standart theraphy is TUR in evry risk groups
• Intravesical instillation of BCG is used in the treatment of high-risk Ta, T1, and CIS
urothelial carcinoma of the bladder.
• Immunotherapy with BCG is the most effective intravesical therapy for CIS and T1 tumors.
• a single dose of bcg is enough in low risk groups however moderate re -tur and 6 dose
bcg ct requiered.
• high risk:second dose recomended. in severe cases ; cystectomy
Treatment of Muscle-Invasive Disease (T2 and Greater)
• 2 methods :
1.bladder sparing (TUR +CT+RT)
2.radical surgery(radical cystectomy(gold standart)uretra uterus sserviks over vajen
ön duvarı prostatitic uretra prostat vesicula semilunaris adıpose tıssue çıkarılır .
bilat pelvic lymphadenectomy)
Treatment of Muscle-Invasive Disease (T2 and Greater)
Radical cystectomy
• The criterion standard for the treatment of patients with stage T2-T4 disease is
radical cystoprostatectomy for men and anterior pelvic exenteration for women.
Cystoprostatectomy
• It involves removal of the bladder, peritoneal covering, perivesical fat, distal ureters,
prostate, seminal vesicles, vas deferentia, and, sometimes, the membranous or
entire urethra.
• Anterior pelvic exenteration consists of cystectomy, urethrectomy, hysterectomy,
salpingo-oophorectomy, and partial anterior vaginectomy.
• Both procedures also include regional lymph node dissection.
Pelvic lymphadenectomy
• Approximately 25% of patients undergoing radical cystectomy have
lymph node metastases at the time of surgery.
• Bilateral pelvic lymphadenectomy (PLND) should be performed in
conjunction with radical cystoprostatectomy and anterior pelvic
exenteration.
• PLND adds prognostic information by appropriately staging the
patient and may confer a therapeutic benefit.
metastatic
• RT:
• non operabl
• for bone mets
• paliation no cure
• systemic CT :
• MOST EFFECTIVE
• cisplatin
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