Urothelial and Renal Cell Carcinomas

Question 1

Normal urothelium locations

Answer 1

Epithelium to most of urinary tract

Papillae to prox urethra

Includes prostatic urethra in men

urothelial carcinoma can arise in any of these locations

Question 2

Normal structure and fx of urothelium

Answer 2

3-5 cell layers thick

Cells change shape as bladder fills and empties…rounded when empty and flattned when full

Luminal surface has uroplakimns

Question 3

Uroplakins benefit nad hamr

Answer 3

Contribute to permeability barrier
Stabilize cell membrane during repeated stretch and fold

Type 1 pili on E coli attach to mannose

E coli persist in the bladder and cause infection

Question 4

Sx of bladder carcinoma

Answer 4

Painless visible hematuria…could have pain as well

Question 5

Risk factors of bladder carcinoma

Answer 5

SMoking

Exposure to dyes, tars, fumes, fertilizers

Increase age and male

Radiation

Chronic irritation (schisto)

prior cyclophos or ifosgamide use

Question 6

Cyclophos

Answer 6

Metabolzied to acrolein which leads to hemorrhagic cystitis and increase bladder cancer risk

Question 7

Sx of urothelial carcinoma in the ureter or kidney

Answer 7

Painless visible hematuria

No bladder sx unless blood clots in the bladder and then difficulty urinating

Flank pain absent unless acute uretral obstruction from blood clot or large invasie kidney tumor

May present iwth other systemic sx

Question 8

Risk factors of urothelial carcinoma or ureter or kidney

Answer 8

Same as bladder cancer

Bladder location omre common than upper tract bc carcinogens pass more quickly through the ureter and stay in the pladder

Upper tract only - HNPCC

Question 9

Hereditary nonpolyposis colorectal carcinoma

Answer 9

Risk factor for urothelial carcinomas of kindey and ureter

Question 10

Urothelial carcinoma exam

Answer 10

Localized to bladder, ureter or kidnye lumen and not large enough to palpate means curable

Advanced dx could lead to other things

Question 11

Dx testds for urothelial carcinoma

Answer 11

Urine tests, cystoscopy, imaging

Question 12

Urothelial carcinoma urine tests

Answer 12

Urinalysis - RBCs and/or WBCs…if clear suspect if acute onset or increase in blsadder sx with signficant risk factors

Culture - not growth

Cytology- carcinoma cells shed to urine…diagnositc if positive…many false negatives

Question 13

Urothelial carcinoma cystoscopy

Answer 13

Office procedure…can look like papillary tumor (cauliflower) or red patch

Question 14

Urothelial carcinoma imaging

Answer 14

CT urogram - IV contrast

If allergic to contrast - MRI urogram with gadolinium or cystoscopy and retrograde pyelogram…instill contrast into ureters from below

Question 15

Renal cell carcinoma

Answer 15

Cleear cell most comon

Question 16

Renal cell carcinoma sx

Answer 16

IF they occur, flank pain and hematuria

Several different paraneoplastic syndromes

Question 17

Renal cell carcinoma paraneoplastic

Answer 17

Hypercalcemia - makes PTH like peptides and osteolytic bone met

HTN - makes renin or compresses renal cessels

POlycythemia - tumor makes EPO

Stauffer syndrome - liver dysfunction from cytokines, NOT liver met

Question 18

Renal cell carcinoma risk factors

Answer 18

Von hippel-lindau
Tuberous slceorissi

End stage renal dx

SMoking, obesity, HTN

Question 19

Renal cell carcinoma exam

Answer 19

Curable is too small to palpate

Varicocele - increase pressure in spermatic veins…dilated veins…usually seen in healthy young men, occassionally singn of retroperitoenal mass

Question 20

Variocele in helathy young men

Answer 20

More common on left bc left gonadal vein drains into left renal vein at 90 angle…in upright, gondal vein is perpindicular to gravity to increase pressure

Right drains into IVC at more gentle slope

Question 21

When would varicocele make you suspect cancer

Answer 21

YOung man with unilateral right varicocele - very unsual…testicular cancer with retroperitneal mass compressing the right gonadal vein

Old man with new…probably kidney cancer

Question 22

Renal cell caricnoma urine tests and imaging

Answer 22

Urine tests - hematuria…cytology not applicable

US can show oslid mass vs. cyst
CT or MRI with contrast cna reveal areas

Question 23

Von-Hippel Lindau

Answer 23

VHL is tumor suppressos

Auto DOM

Usually multiple tumors with clear renal cell carcuinma

About 90% of clear cell have the VHL mutation

Question 24

What does VHL protein do

Answer 24

If hypoxic, makes HIF…in healthy person after hypoxia over, VHL degrades HIF

If defective, HIF not degraded and persistent angiogenic and VEGF

Question 25

VEGF

Answer 25

Stimulate new blood vessel

SOlid tumors outgrow blood supply unless they can make new blood vessels

Blocking VEGF can inhibito growht of solid tumors

Question 26

HIF pathway ingibitors

Answer 26

Clear cell type of renal cell caricnoma

Bevacizumab - monoclonal AB against VEGF