1、Tumors of Urinary systemTypes of tumors in urinary systemUrothelial cancer of BladderRenal cancerProstate cancerTesticular cancerPenile cancerEstimated new malignant cases in North America(2013)Estimated mortality of malignant cases in North America(2013)Prevalence of urological tumors in developing

2、 countries (China)Urothelial cancer of BladderRenal cancerProstate cancerUrothelial Carcinoma (Transitional cell carcinoma)Definition of Urothelial CarcinomaThe epithelium of urinary tract is referred as urothelium or transitional epithelium. The pelvis of the kidney, ureters, bladder, and urethra a

3、re lined by this kind of epitheliumTherefore, the same type of cancers seen in either one of the above organ can also occur in the other sites. (Multi-locus origination)LocationUrothelial Carcinoma of the BladderCompromises 90+% of all bladder cancersOther urothelial malignancies of the bladder incl

4、ude:adenocarcinomasquamous carcinomaurachal carcinomaNon-Urothelial Tumors in the BladderSmall cell carcinomaSarcomas (typically leiomyosarcoma)LymphomasPheochromocytomaCarcinosarcomaMetastatic tumorsIncidence68,810 new cases diagnosed in 2010 in USAThe 4th most common cancer in menThe 11th most com

5、mon cancer in women260,000 new cases diagnosed annually worldwide120,000 deaths worldwide each yearDemographicsGender: Male to Female ratio = 3.5:1 Age: Rates in those aged 70 years and older are approximately 2 to 3 times higherthan those aged 55-69 years, about 15 to 20 times higher than those age

6、d 30-54 yearsRisk Factors for Bladder TCCAge (peak in 7th decade)Incidence in those 70 years and older are approximately two to three times higher than those aged 55-69 years, and about 15 to 20 times higher than those aged 30-54 yearsOccupational exposuresAmines and aniline dyesDye workers, rubber

7、workers, leather workers, truck drivers, painters, and aluminum workersRisk Factors for Bladder TCCCigarette Smoking50% of these cancers in men and 30% in women are due to smokingPhenacetin abuseCyclophosphamide treatment transplant immunosuppressantArsenic, Coffee and Artificial sweetenersPreventio

8、n of Urothelial carcinomaThe greatest prevention strategy is reduction of cigarette smokingCigarette use increases ones risk for bladder cancer by 2 to 6 timesWhen cigarette smokers quit, their risk declines in two to four yearsPathology - GrossPathology- MicroscopicBladder AnatomyFour layers. Impor

9、tant for staging the cancer. Epithelium: Urothelial mucosaLamina propria: a layer of connective tissue and blood vessels under the epithelium. Within the lamina propria, there is a thin and often discontinuous layer of smooth muscle called the muscularis mucosae. This superficial layer of smooth mus

10、cle is not to be confused with the true muscular layer of the bladder called the muscularis propria or detrusor muscle. Bladder AnatomyMuscularis propria (Detrusor muscle): For purposes of staging bladder cancer, the muscularis propria has been divided into: Superficial muscularis propria (inner hal

11、f) Deep muscularis propria (outer half). Perivesical soft tissue: This outermost layer consists of fat, fibrous tissue and blood vessels. When the tumor reaches this layer, it is considered out of the bladderClassification of Urothelial carcinoma of bladderNon-invasive: Ta, T1, TisInvasive: T2-T4Bla

12、dder urothelial carcinoma StageNon-invasiveTaconfined to mucosaT1Invasion into lamina propriaTISIntraepithelial CISNon-invasive urothelial carcinomaAt initial diagnosis, 70% of patients with bladder cancers have non-invasive disease70-80% will relapse4-30% will progress to invasive diseaseInvasiveT2

13、aInvasion into superficial muscularis propriaT2b Invasion into deep muscularis propriaT3a Invasion through muscle into perivesical fat in microscopeT3bInvasion through muscle into perivesical fat in macroscopeT4Invasion into adjacent organsBladder urothelial carcinoma StageInvasive Bladder urothelia

14、l carcinoma30% of urothelial carcinomas invade the detrusor muscle (T2-T4) at presentationHighly aggressiveMay spread by the lymph and blood systems to bone, liver, and lungsSigns and SymptomsHematuria Gross, Painless, Whole range, IntermittentFlank Paindue to obstruction, pelvic mass, or metastatic

15、 diseaseIrritative voiding symptoms (5-10%)Frequency, urgency, dysuriaDiagnosis and Evaluation of Bladder urothelial carcinomaCystoscopy with Biopsy/Resectionsend for pathologyKUB+IVPCT of abdomen and pelvis - assess lymph nodesBimanual exam under anesthesiaCytology FISH(Chrom3,7,9,17 mut)Cytoscopy

16、and BiopsyDescription of bladder mass: Location Size Shape Base AmountIVPUltrasonographyCTMRICytologyNormal urothelial cells uniform appearance abundant cytoplasm small nucleiHigh grade cancer cellBladder cancer cells are enlarged, with large and dark nucleiP16(紅)位點,17染色體著絲粒(綠)3(綠),7(紅)染色體著絲粒P16(紅)缺

17、失,17染色體多體3,7染色體多體正常人患者TreatmentNon-invasive diseaseTransurethral resection (TUR-Bt)Immediate instillation (within 24h after resection)Routine instillation (every week for 6-8w)Maintenance instillation (every month till 1y)Radical cystectomy is seldomRegular surveillance with cystoscopy (every 3m)Tre

18、atmentPostoperative intervention drugsChemotherapyMitomycin C (most effective)Others include Doxorubicin and thiotepaIntravesical immunotherapyBCG (bacille Calmette- Guerin)improved response with addition of alpha-interferon if failed with BCG aloneTreatmentInvasive disease (Stage T2 or greater)Radi

19、cal Cystectomypatients will require urinary diversion50% of patients with muscle invasive TCC will have metastatic disease at diagnosisCystectomy not curative and additional therapy needed with metastasesNeo-adjuvant chemotherapyAdjuvant chemotherapyTreatmentMuscle invasive TCCSelect patients (Stage

20、 T2) may be treated with transurethral resectionPartial cystectomy may be an option in select patients with unifocal disease away from the ureteral orifices and bladder floor in whom 2 cm margins are attainableTreatmentThe role of Chemotherapy Neo-adjuvant chemotherapyNeo-adjuvant chemotherapy showe

21、d survival benefit in the treatment of invasive bladder cancer, especially in pts with T2-T3 stageNeo-adjuvant chemotherapy could reduce 16% of death risk in pts with bladder cancerMeta-analysis: improvement of 5-year OS and PFS is 5% and 9%, respectively.Adjuvant chemotherapyThe clinical value of a

22、djuvant chemotherapy after surgery is still controversial, due to lack of large scale prospective RCTs.Metastases with Invasive TCCLymphaticpelvic lymph nodesHematogenous metastasesliverlungboneadrenal glandbowelMetastatic or Unresectable TumorsPlatinum-based chemotherapy GC used most commonlyMVAC (

23、classic regimen)Radiation therapyInterventional therapyBio-therapyEnrolled into Clinical TrialSurvivalNon-invasive (Ta, Tis, T1)70% at 5 years with TURBt80% at 5 years with cystectomyRecurrence66% at 5 years overall88% at 15 years despite resection15% with muscle invasive diseaseBCG decreases recurr

24、ence to 17-55% with one 6 week coursebest for CISSurvivalInvasive (T2, T3, T4)Radical cystectomyT245-70% at 5 yearsT335-60% at 5 yearsRadiation TherapyT1, T240% at 5 yearsT3, T420% at 5 yearsN1,N2 (nodal metastases) 7% at 5 years50-70% recurrence rateProgressionTCC is a progressive diseaseGrade 110-

25、20%Grade 220-35%Grade 335-65%Surveillance is keyCystoscopyUrinalysis + B ultrasound + cytologyNewer approaches in researchRenal Cell CarcinomaEpidemiologyResponsible for 80-85% of primary renal neoplasms54,390 newly cases in USA in 2010The 7th and 9th common malignancies in men and female, respectiv

26、ely Incidence increased gradually over past 30 yrs (2-3% per year)Approximately 12,000 deaths/year Incidental FindingsIncidential Finding:A large number of RCCs now are discovered as an incidental finding due to abdominal CT or ultrasound performed for abdominal pain, trauma, or in the work-up for o

27、ther medical problemsIn a 1971 review, hematuria, abdominal mass, pain, and weight loss most common presentation. Only 10% were discovered incidentally in the 1970s, compared to 61% in 1998. 25% metastases at diagnosisRisk factorsRisk factorsSmoking (2 fold):The longer a person smokes, the higher th

28、e risk. Decreased for those who quit.Occupational exposure: Possibly asbestos, cadmium or gasoline exposure (1.42 fold)Acquired cystic disease of the kidney (30 fold)ACKD occurs in 35-50% of chronic dialysis (usu after 8-10 yrs of dialysis)Phenacetin: ? No longer sold in the United StatesOther risk

29、factors - geneticVon Hippel-Lindau disease (1/3 get RCC)Autosomal dominantAbnormalities in chromosome 3pHereditary papillary RCCMutated c-met oncogene (chromosome 7p)Tuberous sclerosis (95% accuracy. If not clearly a cyst CT. D/Dx mainly RCC, hamartoma, xanthogran pyeloIVPCT scanPlain scan Enhanced

30、scanCT scan CT scan: 91% accurate for staging (as compared to stage after surgery) 98% sens, 96% spec for renal vein invasion 83% sens, 88% spec for metastatic LAD 46% sens, 98% spec for perinephric invasion 100% spec for adjacent organ invasionMRI MRI is useful if IVC or atrial involvement suspecte

31、d and to identify extent of IVC involvement.Retrograde PyelogramAngiographyRenal arteriography- D/Dx Useful if nephron sparing approach plannedMetastatic Work-upChest X-rayCTAbdomen and Pelvis: lymphadenopathy or elevated liver function testsHead/Chest (mental status changes, lung lesions)Bone scan

32、esp if T3a or if nodeswith bone pain PET scan may be more sens for bony metsMetastatic Work-upLaboratory TestsLiver Function Tests (LFTs)Serum CalciumSites of metastases include:Lung (69%) Bone (43%) Liver (34%) Lymph Nodes (22%) Adrenal gland(s) (19%) Brain (7%)TNM classification of RCC(2004)TNM cl

33、assification of RCC(2010)TreatmentRadical NephrectomyPartial Nephrectomy (nephron sparing)Laparoscopic NephrectomyTarget molecule therapyImmunologic TherapyRadiationChemotherapySurgical managementStage I (7cm but limited to kidney, no nodes or mets) partial or radical nephrectomyPartial if Bilateral

34、 tumorsPatients with solitary kidneyChronic Renal Insufficient Small (4cm) or tumor at poleLaparo nephrectomy possible if mass cells (+) for MDR, PFS 4mo vs 27 moAttempts to use MDR modifiers like CsA or PSC 833 have so far been unrewardingPalliative / supportive carePain, bleedingAnalgesic medicationsXRT to sites of painful mets (esp bone mets)XRT for cord compressionAngioinfarction (re