ICL 5.5: Malignancies of the Ureter and Bladder

Question 1

what are the types of congenital anomalies of the bladder?

Answer 1

1. vesicoureteral reflux

2. extropy

Question 2

what is extrophy?

Answer 2

aka congenital vedic-cutaneous fistula

there’s an incomplete closure the anterior abdominal wall and the anterior bladder wall

this leads to exposure of the bladder mucosa which leads to irritation, infection etc.

Question 3

what causes extrophy?

Answer 3

overgrowth of cloacal membrane

Question 4

what are the complications of extrophy?

Answer 4

1. acute and chronic infections
2. metaplastic changes (due to chronic infections and irritation) (adenomatous or squamous changes)
3. risk of neoplastic transformation

Question 5

what metaplastic changes can happen in the bladder due to chronic infection/irritation?

Answer 5

1. swuamout metaplasia schistosomiasis

2. adenomatous metaplasia

Question 6

what are the inflammatory diseases of the bladder?

Answer 6

1. chronic interstitial cystitis (Hunner’s ulcer)

2. malakoplakia

Question 7

45 year old women present with urge to empty her bladder every 30-40 minutes. this is sometimes associated with suprapubic pain.

UA: negative, no cells, no blood

esterase negative

nitrites: negative

cystoscopy reveals edematous mucosa with
focal ulcerations

diagnosis?

Answer 7

Hunner’s ulcer

if it was cystitis, there would’ve been WBCs and RBCs

esterase and nitrites are negative which also doesn’t indicate UTI

so it looks like acute infectious cystitis but it’s definitely not….there’s edema and ulcerations of mucosa

Question 8

what is Hunner’s ulcer?

Answer 8

1. middle age women
2. suprapubic pain
3. frequency
4. urgency
5. edema, ulcerations and granulation tissue

pathologenesis thought to be autoimmune

Question 9

what are the components of granulation tissue?

Answer 9

1. fibroblasts/collagen
2. lymphocytes/macrophages
3. new blood vessels

Question 10

A 35 year old, 9 years post renal transplant patient, presents with what appears to be recurrent urinary tract infections for the last 3 years. He had multiple negative cultures as well as empirical antibiotic therapy with no improvement.

Cystoscopy reveals multiple calcified mucosal plaques.

Answer 10

post-renal transplant = immunosuppressants

Question 11

what is malakoplakia?

Answer 11

usually seen in immunosuppressed patients

raised mucosal plaques made of:

1. large foamy macrophages PAS positive
2. occasional giant cells
3. ymphocytes

intracellular concretions “Michaelis-Gutman bodies”

they are laminated concretions resulting from deposition of calcium in enlarged lysosomes**

pathogenesis chronic infections

Question 12

what is cystitis glandularis and cystitis cystica?

Answer 12

downward growth of transitional epithelium “Brun nests” into lamina propria with metaplastic changes –> if it is just down growth, it’s cystitis cystica but if there metaplasia with gland formation it’s cystitis cystica

most commonly glandular

occasionally seen in normal bladder but usually in chronically irritated bladder

Question 13

what are the complications associated with cystitis glandularis?

Answer 13

adenocarcinoma with the cystitis glandularis

Question 14

what is the blood supply of the bladder?

Answer 14

superior and inferior vesical arteries which are branches of the anterior division of the internal iliac artery

Question 15

what is the venous drainage of the bladder?

Answer 15

inferior and superior vesical veins, which in turn drain into the internal iliac vein

Question 16

what is the lymphatic drainage of the bladder?

Answer 16

level I nodes(internal iliac, obturator,andexternal iliac which drain into..

level II nodes: common iliac, presacral) which drain into..

level III nodes: paracaval, para-aortic,andinteraortocaval

Question 17

what is the urothelium?

Answer 17

the epithelium that lines the urinary tract and extends from the tip of the renal papillae to the urethra

typically has3-6 layers of cellsthat are comprised of (from basement membrane to lumen)basal cells, intermediate cells, and umbrella cells

Question 18

what layer of the urothelium is bladder cancer though to arise from?

Answer 18

1. basal cells
   ex. CIS, muscle-invasive urothelial carcinoma, and squamous cell carcinoma
2. intermediate cells in some cases
   ex. non-invasive urothelial carcinoma

Question 19

65 year old smoker presents with painless hematuria.

UA: many RBC’s

Metabolic Panel: within normal limits

Cystoscopy: one ulcerated lesion at the dome

Biopsy: urothelial carcinoma of bladder

Answer 19

(:

Question 20

how common is bladder cancer?

Answer 20

bladder cancer is the fourth most common cancer in men and the fifth most common malignancy overall

in the United States in2019,80,470new cases of bladder urothelial carcinoma

male to female ratio is 4:1, with an age standardized incidence rate of 10/100,000 for males and 2.5/100,000 for females.

1 in 26 malesand1 in 87 femaleswill develop bladder cancer over the course of their lifeand17,670deaths from bladder cancerare expected to

caucasians are more likely to develop bladder cancer than other ethnic groups

Question 21

how does age effect bladder cancer?

Answer 21

increase in incidence with age such thatmen over 70 have a 3.7% probability of developing bladder cancer compared with 0.92% of men 60 to 69 and 0.38% for men 40 to 59

Question 22

what are the risk factors for developing cancer?

Answer 22

1. current smoker
2. former smoker
3. aromatic hydrocarbons (metal processing, truck drives, oil and coal production)
4. aromatic amines (textiles, painters, hairdressers, chemical plant)
5. n-nitrosamines
6. blackfoot disease (arsenic exposure in Taiwan)
7. formaldehyde
8. Lynch syndrome
9. U-Fraumeni syndrome
10. chronic cystitis (recurrent UTIs, indwelling foley, schistosome, bladder stones can cause SCC)
11. radiation
12. cyclophosphamide
13. pioglitazone

Question 23

which genes are associated with bladder cancer?

Answer 23

1. NAT1
2. NAT2
3. GST gene

Question 24

what is the non-invasive pathway in development of bladder cancer?

Answer 24

characterized by mutations in oncogenes FGFR3 and PIK3CA as well as loss of heterozygosity on chromosome 9q

can develop non-muscular invasive cancer

Question 25

what is the invasive pathway in development of bladder cancer?

Answer 25

characterized by mutations in the TP53 and RB1 tumor suppressor genes can develop muscle invasive bladder cancer

Question 26

what are the most common histologies associated with bladder cancer?

Answer 26

1. urohtelial carcinoma of the bladder -- MOST common 2. squamous cell carcinoma (3-7%, bladder stones, diverticuli, chronic infections, or bilharziasis) 3. adenocarcinoma at dome 4. non-urothelial bladder tumors: small cell, carcinosarcoma 5. non-epithelial bladder tumors: neurofibroma, pheochromocytoma, lymphoma, sarcomas

Question 27

what are the signs and symptoms of bladder cancer?

Answer 27

1. hematuria (most common presenting symptom) | 2. irritative voiding symptoms

Question 28

what type of bladder cancer is associated with irritative voiding symptoms?

Answer 28

carcinoma in situ primary symptoms, such as urgency, dysuria, frequency and nocturia, or be mis-diagnosed as recurrent bacterial cystitis

Question 29

what are the 2 types of hematuria and how are they defined?

Answer 29

1. microscopic hematuria dipstick isn't sufficient, 3+RBCs per high power field is microscopic hematuria 2. gross hematuria

Question 30

what are the diagnostic tests for hematuria?

Answer 30

1. cystoscopy 2. urine cytology (not super sensitive for low grade cancers but it's good for high risk cancers 3. CT urography) 4. retrograde pyelography 5. ureterscopy

Question 31

what is CT urography?

Answer 31

single best imaging modality for evaluation of urinary stones, renal and peri-renal infection, renal cell carcinoma, urothelial carcinoma of pelvicaliceal system or ureter

Question 32

what is a retrograde pyelography?

Answer 32

done at cystoscopy or transurethral resection of bladder tumor (TURBT) it is another acceptable method of screening the upper urinary tracts for urothelial cancer

Question 33

what is a ureterscopy?

Answer 33

if there are suspicious filling defects seen on the retrograde pyelograms then subsequent ureteroscopy (+/- biopsy) should be performed it's a camera in the ureter to look at it and if you need you can take biopsy too

Question 34

is invasive or noninvasive bladder cancer more common?

Answer 34

75% of bladder cancers are non-invasive on diagnosis 25% are invasive on diagnosis treatment is based on grade and stage

Question 35

what are the stages of bladder cancer?

Answer 35

stage 0: if it is carcinoma in situ, papillary tumor just in the mucosa stage 1: tumor has growth into the lamina propria stage 2: if the tumor has grown into the muscle; higher rates of metastasis stage 3: if the tumor is in the fat outside the bladder stage 4: mets

Question 36

a 60 year old has a muscle invasive urothelial carcinoma on TURBT. The preoperative CT scan shows loss of fat plane on right side of the bladder. Patient has a clinical stage: ``` A- T2 B- T1 C- T3a D- T4 E- T3b ```

Answer 36

T3b it's macroscopic loss of fat, not microscopic

Question 37

what doe the course of bladder cancer treatment depend on?

Answer 37

depends on grade and stage!! presence of blood group antigen is associated with good prognosis presence of chromosome abnormalities and gene mutation is associated with poor prognosis

Question 38

what are low grade bladder tumors?

Answer 38

usually papillary DNA is usually diploid no or limited chromosome or gene abnormalities retains blood group antigen

Question 39

what are high grade bladder tumors?

Answer 39

papillary or nodular DNA is usually aneuploidy marked anaplasia high frequency chromosomes and gene abnormalities lack blood group antigens

Question 40

what is TURBT?

Answer 40

Transurethral Resection of bladder Tumor = diagnostic AND therapeutic! because you remove and biopsy the tumor small tumors can be removed with cold cup biopsy forceps and the biopsy crater and surrounding urothelium (important due to field effect) can be fulgurated larger tumors require the use of an endoscopic resectoscope. 

Question 41

what are the indications for a second TURBT?

Answer 41

a second-look (repeat) TURBT is sometimes done within 2-6 weeks of the first TURBT the indications for this include: 1. incomplete first TURBT 2. large (> 3 cm) or highly multifocal tumor 3. high grade Ta tumor and T1 tumor when a second TURBT is done Ta 50% had residual disease and 15% were upstaged and with T1 tumors, 48% had persistent NMIBC and 30% were upstaged to muscle invasion --> this is why it's so important to do the second TURBT! the AUA guidelines recommend that in a patient with high-risk, high-grade Ta/T1 tumors, a clinician should consider performing repeat transurethral resection of the primary tumor site within six weeks of the initial TURBT

Question 42

how do you treat noninvasive bladder cancer?

Answer 42

based on stage and invasion! 1. surveillance with repeat resections as needed 2. intravesical therapy mitomycin-C or Gemcitabine or epirubicin within 24 hours of TURBT or six week course of induction intravesical chemotherapy or immunotherapy (BCG) with maintenance therapy

Question 43

how do you treat muscle invasive bladder cancer?

Answer 43

neoadjuvant chemotherapy followed by radical cystectomy with urinary diversion radiation with chemotherapy

Question 44

what are the general pearls for treatment of bladder cancer?

Answer 44

the standard induction course is the same for immunotherapies and chemotherapies, and is given weekly for a total of 6 doses and then cystoscopy is done 6 weeks later to assess for response patients must retain the drug for two hours for peak efficacy patients should not drink for 4-6 hours prior to treatment clinical trials have demonstrated benefit for maintenance therapy for both mitomycin C and BCG the most common maintenance schedule for BCG is the Lamm/SWOG regimen (triplets of BCG given at 3, 6, 12, 18, 24, 30 and 36 months) the most common maintenance schedule for chemotherapy is once monthly for 1-3 years

Question 45

what are the risk factors for upper urinary tract neoplasms?

Answer 45

1. smoking 2. bladder cancer 3. Lynch 4. Balkan nephropathy, Chinese and Taiwanese herbal nephropathy 5. arsenic 6. analgesics 7. occupational exposure 8. chronic inflammation and infection 9. cyclophosphamide

Question 46

what are the clinical signs and symptoms of upper urinary tract urothelial carcinoma?

Answer 46

1. hematuria 2. flank pain 3. dysuria 4. symptoms of advanced disease 5. common mets to the liver, lungs, bones, regional lymph nodes

Question 47

what are the risk factors for advanced upper tract urothelial carcinoma?

Answer 47

1. tumor grade 2. positive cystology 3. sessile tumor architecture 4. multifoacility 5. hydronephrosis 6. tumor size 3+ cm

Question 48

what is the nonsurgical treatment of upper tract urothelial carcinoma?

Answer 48

1. intracavitary therapy: bacillus, calmette, guerin (BCG), mitomycin C 2. neoadjuvant chemo 3. surgical management: partial ureterectomy or radical nephroureterectomy

Question 49

``` 65 year old male with a solitary 3.0 cm low-grade appearing papillary tumor endoscopically resected. Next step? 1- Intravenous chemotherapy 2- Intravesical chemotherapy 3- Intramuscular chemotherapy 4- Oral chemotherapy ```

Answer 49

2- Intravesical chemotherapy solitary, first time presenting with polyp, so just 1 dose of chemo via catheter

Question 50

35 year old Egyptian farmer presents with hematuria and suprapubic pain. Past medical history: treated for schistosomiasis when he was 28 years. UA: RBC’s and epithelial squames Cystoscopy: fungating mass Biopsy: Histology type?

Answer 50

squamous cell carcinoma

Question 51

A 75 year old male presents with 6 months of painless hematuria. He has a past medical history of prostate cancer treated with radiation 7 years ago. UA: negative Urine Culture: negative DD: Pathogenesis:

Answer 51

prostate cancer with radiation treatment in the past so he maybe got bladder cancer from the radiation but do cystoscopy and upper tract imaging to check -- UTI should also be on the differential but ultimatelyl he probably has radiation cystitis where blood vessels rupture because they became brittle and rupture