UPPER URINARYTRACT T.C.C.

Anwar EsawiR4

K.K.N.G.H.

CONTENT

►Epidemiology►Risk factors & associations►Natural history►Diagnosis►Staging►Treatment►Summary►Studies

Epidemiology

►Renal pelvic ca. is 10% of renal tumor.►5 % of urothelial tumor.►Ureteric tumor is 1% of urothelial

tumor. ( 73% :distal , 24% :mid , 3% : prox. )►> 90% of upper urinary tract tumor is

T.C.C.►M : F is 3 : 1►W : B is 2 : 1

Epidemiology

►10/100000/year in white male .►Peak age is 75—79 years .►2 – 5% is bilateral , syn or asyn.►2-4 % inci. Of upper tract TCC in pts with

bladder TCC.►20% risk of upper urinary tract TCC in

bladder CIS at 10 y.►40-80% risk of bladder TCC in upper tract

T.C.C. pt.

Risk Factors

► Mostly: age,gender,race,smoking & Balkan nephropathy.

Balkan neph.: interstitial nephropathy, in rural areas of

Balkan countries100-200*inci. Of upper tract T.C.C. in

these families.Generally low grade,multiple & bilateral

more than other T.C.C.

Risk Factors

►Analgesics: phenacetin increase risk by 3.6*, become 20* if combined with papillary necrosis.

Long-term analgesics can cause nephropathy that has 70% inci of upper T.C.C.

( Thickening of BM around subepithelial capillaries- capillosclerosis )

Risk Factors

► Coffee► Ocupational factors: chemical,petrochem. Plastic

industries,coal,coke,asphalt,tar.► Chronic infection & irritation calculi: predispose to

S.C.C. or adeno.► Cyclophosphamide: most of these ca. are high

grade & aggressive.► Hereditary: Lynch syndrom ll is a familial proximal

colonic nonpolypotic ca. with extracolonic ca. mostly endometreal,may have increase risk of upper T.C.C.(molecular alteration –Ch9,17,13), female predominance.

Risk Factors

►Smoking: Nitrosamines,2-naphthylamine , 4-aminobiphenyl and increased urinary tryptophan metabolites all are carcinogenic agents of smoking .

Patterns of spread

►Epithelial spread: cephalad to caudad►Lymphatic extension: paraaortic ,

paracaval , ipsilateral common iliac & pelvic L.N.

►Hematogenous dissemination: mostly lung , liver , bone .

Increase spread with high grade.95% mets with hilar invasion.

DIAGNOSISSymptoms & Signs

►Mostly gross or micro hematuria > 75% .

( Long thin clots suggest upper source) Dull flank pain in 30% (since gradual

obs.)( Acute colic if clot obst.) 15% Dx. Incidentally. 10% Abd. Mass . CVA tenderness .

DiagnosisImaging

►I.V.P.: radiolucent filling defect 50-70% (Irrigular & continuity with wall)

Non-function 2ry to obst.D/D of filling defect : ca.,radiolucent

stone, slough renal papilla, blood clot, bowel gas, crossing vessel, fungus ball, fibroepithelial polyp, air bubble, granuloma, leukoplakia, hemangioma, T.B., leiomyoma

DiagnosisImaging

►Retrograde pyelography : use non-ionic contrast.

Helpful if I.V.P. showing non-functioning kidney due to obst.

Urine cytology can be collected by barbotage.

Brush biopsy can be taken over catheter not URS bec. Fear of seading.

Antegrade pyelography: not used,fear of seading along needle tract.

DiagnosisImaging

► C.T.Scan: Dx. & staging. Diff. T.C.C. from uric acid stone. Soft tissue mass with density of 46 HU T.C.C. is hypovascular, so low density after

contrast not like R.C.C. M.R.I.: no adv. Over C.T. U/S : Little value in definitive Dx. And

staging. Renal Angiography . NO STUDY CAN DIFF. Ta FROM T2

DIAGNOSISProcedures

► Cystoscopy: 1. Look for coexistent bladder ca.2. Which tract produces hematuria3. Cytology: ureteral cath. washing is

more accurate but 25% false_ve, also false +ve with hyperosmotic contrast.

4. Brush Bx.: over cath. not URS d/t risk of bleeding,perforation & spread of tumor . 90% sens,88% spec,89% accuracy

DIAGNOSISProcedures

► Ureteroscopy & Nephroscopy :1. High Dx. accuracy:86% of pelvic,90%

ureteric .2. Not needed if +ve cytology&filling defect.3. Comp.; perf.,stricture, pyelo-veno-

lymphatic migration .4. Nephroscopy: risk of seeding , not

encouraged.5. Intraluminal U/S .

STAGINGTNM Staging System

Ta : epithelial confined, usually papillary. Tis : CIS . T1 : lamina propria . T2: muscularis propria . T3: peripelvic/periureteric tissue or renal

parenchyma . T4 :contiguous organs .

► N1 : L.N. <= 2 cm.► N2 : L.N. >2 <=5cm or multiple L.N. < 5 cm.► N3 : L.N. > 5 cm.

……………………………………….. MO : no mets. M1 : distant mets.

Metastatic Evaluation

C.T.Scan : Look for liver mets . Cant diff. Ta & T2 . Poor accuracy of fat invasion or periureteric

extension . Failure to detect multifocal lesions . Good for large tumor . CXR , Bone scan , LFT . Renal scan & split renal function , Cr

clearance if compromised renal function .

Poor prognostic factors

► Tumor > 1.5 cm .► High grade .► Multifocality . Ceasation of ABH blood group antigens expression

on tumor cells correlate with increase recurrence rate .

DNA Flow Cytometry :1. Oldbring(1989)reported that all G3 & 50% of G2

tumor are aneuploid2. Blute(1988)found correlation among tumor cell

DNA ploidy,grade,stage & clinical outcome .3. Corrado(1991)found correlation bet.

ploidy&survival . P53 mutation has important role in tumor

development & progression .

Treatment► Must Dx. & look at opposite side .► Must R/O multiple tumors on affected side.► Low grade&stage pt. do well with conservative or Rad. Sx.► Intermediate grade better with Rad. Sx.► High grade&stage poor with either thus ;1. Most pelvic ca. Nephroureterectomy .2. Upper&Med uretersegmental resection if solitary&low

grade , NephroU. if multifocal & mod. diff.3. Distal U. distal ureterectomy & ureteroneocystostomy if no

multifocality & low grade .4. Solitary kidneypreserve func. by conservative resection ,

endourologic Tx., Autotransplantation, Antegrade instillation Tx.

► +ve cytology but –ve Radio.&endoscopic exam pt. F/U with RGP & IVP and not to Tx. blindly .

Treatment options forlow grade & stage

►Nephroureterectomy .►Open pyelotomy .►Partial nephrectomy .►Segmental resection .►Distal ureterectomy & re-implantation .►Pyeloureteroscopy .►PCN .

Treatment by grade

Grade 1 : 1. 5 YRS is 88%(Rad.) vs 75%(conservative).2. Recurrence rate from Rad. is 5% . Grade 2 :1. Radical is Tx. of choice .2. 80 % 5YRS . Grade 3 :1. 40% have +ve L.N.2. 60% 5YRS .3. 50% Recurrence .

Treatmentby location

Pelvis :1. 50% recurrence after local resection .2. 10% have CIS . Upper/Medureter :1. Segmental resection if solitary and low grade .2. 30% recurrence rate .3. NephroU. If multiple or mod/high grade . Distal :1. Distal ureterectomy/reimplant if not multifocal &

low grade .2. 100 % survival if G1 and treated as so .3. High grade NephroU.

Radical Nephroureterectomy

►30—75% risk of recurrence in ureteral stump if complete distal ureterectomy & bladder cuff was not done .

►Wether you do 1 or 2 incisions, its important not to transect the ureter to avoid tumor spillage .

►Do anterior cystotomy to ensure good cuff taken & other orifice is not damaged .

Radical Nephroureterectomy

► Regional lymphadenectomy :1. Remove ipsilat. renal hilar,paraaortic &

paracaval nods in renal pelvic,proximal or middle ureter tumor .

2. Remove ipsilateral deep pelvic nodes in distal ureteric tumor .

► 5YRS :1. 90% for Ta,Tis and T1 .2. 43% for T2 .3. 23% for T3—4 ,N1—2 .4. 0% for N3,M1 .

Patient in torque flank position for radical nephroureterectomy through a single thoracoabdominal incision. The shoulder girdle is rotated into a full flank position. The pelvic girdle is rolled back

nearly to a supine position. All potential pressure points are carefully padded

Radical nephroureterectomy may be performed via a long midline incision or through a subcostal plus Gibson, lower midline, or Pfannenstiel incision. The patient is supine, and the table is mildly flexed. Placing a small roll under the

edge of the rib cage is helpful

►Radical nephroureterectomy specimen including the kidney, Gerota’s fascia, perinephric fat, with or without the ipsilateral adrenal gland. Note that the ureter is divided distally in the pelvis between ties for a separate distal ureterectomy

Conservative TreatmentIndications

1. Solitary kidney .2. Bilateral tumors .3. Compromised contralateral renal unit

.4. Overall compromised renal function .5. Unstability to tolerate long procedure

.

Conservative Treatment

► Overall recurrence risk in the ipsilateral renal pelvis after pyelotomy & partial nephrectomy varies from 7% to 60% .

► Risk of recurrence increase with tumor grade ;1. G1 < 10%2. G2 & G3 28%--60% ► Murphy(1980),reported 5YRS of 75% & 2YRS of

46% after conservative surgery in pts. With G1 and G2 renal pelvic tumor,respectively .

► Rad. nephroU. & dialysis still offer the best chance of cure&survival in pts. with large,invasive,high-grade organ confined renal pelvic tumor(T2,N0,M0) in a solitary kidney .

Open SegmentalUreterectomy

►Indicated for noninvasive G1&G2 of proximal or midureter that too large for complete endoscopic ablation & for G3 or invasive tumor when nephron sparing for preservation of renal func. is a goal .

►Complete distal ureterectomy is recommended for distal ureter tumors that cannot be removed completely by endoscopic means .

Open SegmentalUreterectomy

►McCarron(1983)reported 5YRS of 64% for Ta pts. treated by either segmental ureterectomy or endoscopic tumor ablation,5YRS of 66%&50% for T1&T2 , respectively treated with segmental or distal ureterectomy .

►Anderstrom(1989)reported segmental ureterectomy in 21 pts. with low grade , noninvasive tumor & F/U for a median of 83 mon. 1 recurrence & no tumor-related deaths .

► Ipsilat. recurr. post conserv. Ureteral tumor Tx. is 33% to 55% .

►McCarron(1983)reported 5YRS of 64% for Ta pts. treated by either segmental ureterectomy or endoscopic tumor ablation,5YRS of 66%&50% for T1&T2 , respectively treated with segmental or distal ureterectomy .

►Anderstrom(1989)reported segmental ureterectomy in 21 pts. with low grade , noninvasive tumor & F/U for a median of 83 mon. 1 recurrence & no tumor-related deaths .

► Ipsilat. recurr. post conserv. Ureteral tumor Tx. is 33% to 55% .

Endoscopis Management(Ureteroscopic Tx.)

► Prefered over perc. Since no spillage .► Needs strict F/U since high recurrence .► Tawfick&Bagley(1997)reviewed 205 pts. 1. 33% recurrence in ureteral lesions.2. 31.2% recurrence in pelvic lesions .► Most imp. prognostic factor for recurr.is

grade.► Keeley(1997)reported recur. rate 26% for

G1 & 44% for G2 .

Endoscopis Management(Ureteroscopic Tx.)

► Indications :1. Solitary kidney .2. Bilateral tumor .3. Compromised contralateral renal

func.4. Overall compromised renal func.5. Poor surgical candidate .6. Preoperative evidence of single , low-

grade tumor .

Endoscopis Management(Ureteroscopic Tx.)

► Complications :1. Perforation & extravasation .2. Seeding & recurrence .3. Pyelo-veno-lympho. back flow .4. Bleeding .5. Stricture(5—13%)(better results with

laser) .

Percutanious Tx.

►Indications: same as ureteroscopic Tx. but to tumors not amenable to ureteroscopic excision .

►Recurrence : G1:15%,G2:30%,G3:50% .

►Risks: Bleeding,Seeding,Spillage & all comp. of perc.

► Advantages: Larger scopes , instillation Tx. can be used .

Instillation Tx.

►All studies describes small,retrospective, uncontrolled series of pts. Tx. with thiotepa,MMC or BCG .

►No statistical improvement in survival or recurrence rate .

►Complications: scarring,obst.,BCGosis (systemic absorption greater than in bladder).

►Methods of delivary: PCN(best),retrograde , refluxing ureter .

Radiation Tx.

►Used as adjuvant therapy post surgical Tx. of T3,4,N+ .

►Results: Does not decrease local relapse nor protect against a high rate of distant failure .

Systemic Chemotherapy

►Very limited data on response rates of advanced upper tract tumors to chemo are availabe owing to the rarity of these lesions .

►Therefore, one must take advantages from observations in bladder cancer trials . (Cisplatinum)(Gemcitabin)(Paclitaxel) ets.

►Overall survival of 12 to 24 months .

STUDY (Int J Urol.2006 Jan)Dep of uro,Hamamatsu Univ School of Medicine,Japan

Mugiva,Ozono,Nagata,Otsuka,Takayama,Nagae .► Objective: to investigate the efficacy of endoscopic laser Tx.

& URS surveillance for upper tract TCC .► 7 Pts.:5 with G1, 2 with G2. 1.3 cm avarage tumor size.► Results: 1. 1 pt with large,multifocal tumor died of metastasis.2. 1 pt died of an unrelated cause.3. 1 pt requested nephroU. after endoscopic Tx.4. 4 pts were F/U for a mean of 32 mon,each pt received

avarage 5.3 URS surveillance while 3.3 recurrences on avarage were detected.

5. Recurrence occurred in all pts showed normal radio finding .6. Cytology was of little value in predicting recurr. except in 1

(cis).7. 3 pts of 4 remained alive& 1 pt with G2 died of recurr after

30 mon.► Conclusions: Pts treated endoscopically should be

recommended to undergo long_term endoscopic follow up .

Study (Cancer2003Jul)Dep of uro,Uni of South California,Keck school of

medicine, L.A.,USADaneshmand,Quek,Huffman

► Objective: efficacy & long term results of endoscopic Tx. of upper TCC.

► Method: bet 1987and2001,50pts(17with solitary kid)► 11pts underwent ureterectomy or nephroU shortly after

URS&biopsy, there were no F/U► 30 pts underwent URS&laser or electrofulguration & URS

surveillance at 3_4 mon intervals :1. Mean 38 mon F/U(4_106mon)2. 3.4 avarage recurrences with avarage time to 1st recurr of

7mon3. 10 pts underwent open resection during F/U4. 6 pts exhibited tumor progression at F/U5. 1 pt died of recurr & 6 died of other causes► Conclusion: Endoscopic Tx of focal,low grade TCC upper

tract is feasible and safe,provided that vigilant F/U & endoscopic surveillance are performed .

Study(Urology2005Aug.)Dep.of Urology,New York Presbyterian Hosp-Weill-Cornell Medical

Center.USA.BOORJIAN,MUNVER,SOSA,DEL PIZZO,VAUGHAN,SCHERR

► Objectives ;to investigate whether a delay in nephroU. for pts with TCC upper urinary tract owing to ureteroscopic biopsy and/or laser tumor ablation affects postoperative disease status.

► Methods ; 1. (19932003)2. 121 pts underwent nephroU. out of 155 pts with upper tract TCC.3. 75 pts post +ve ureteroscopic biopsy, 34 pts after +ve cytology&filling

defect on contrast imaging (no URS) ,12 pts post URS biopsy& laser tumor ablation.

4. Results: Mean follow up of 38.7 months 29(85.3%) of the 34pts group were disease free, 61(81.3%) of the 75 pts

group were disease free & 10(83.3%) of the 12 pts group were disease free .

CONCLUSIONS: Ureteroscopy with biopsy and/or tumor ablation before nephroureterectomy did not adversely affect the postop. disease status.

Study(Urology2001Aug.)Dep. Of Urology,Mayo Clinic,Rochester,Minnesota,USA

Elliott,Segura,Lightner,Patterson,Blute

► Objectives : to evaluate the endoscopic management of upper tract TCC as a first-line treatment in pts with a normal contralateral kidney ( Long-term experience ) .

► Methods : 1. 21 pts with upper tract TCC were treated with conservative endourologic

techniques using either laser or electrocautery2. Follow up for a mean of 6.1 years(range 111.6)► Results : 1. 8 renal pelvic TCC while 13 ureteral TCC2. All stage T1 or less, < 2 cm,G3 or less3. 7 of all(33%) had one local recurrence,1(4.7%) had 2 local recurr.4. 6 of ureteral(46%) recurred,1 of 8 renal pelvic(12%) recurred5. No change in grade in recurrence6. 17 out of 21(81%) were preserved,4(19%) required nephroU.7. 11 pts died(10 of non-TCC etiology&1 secondary to invasive bladder TCC)► CONCLUSIONS : conservative endourologic treatment of upper tract TCC is

an evolving field;however, in properly selected pts, endoscopic treatment can be safely and effectively used as a first-line treatment for upper tract TCC.

Conclusions

►Conservative Tx. needs close F/U .►Segmentl resection when renal

preservation is necessary .►High grade or pelvic lesion are not

suitable for local resection .►Focal , low grade are ideal for local

resection .►Low grade pelvic tumor : conserv. vs.

aggressive Tx.