Wilms' Tumor

							Wilms’ Tumor
D.K Gupta, Prof.and Head




    Department of Pediatric Surgery
 All India Institute of Medical Sciences
            New Delhi, INDIA
  DKG /SAAPS/2008
Wilms tumor : 6% of childhood cancer
• National Wilms’ Tumor Study (NWTS)
• Société Internationale d’Oncologie Pédiatrique (SIOP)
• UK Children Cancer study Group (UKCCSG)
• Children Oncology Group (COG)


• Intensifying treatment for high risk cases
• Reduce long-term complications
• Identify favorable prognosticators

 DKG /SAAPS/2008
                  Imaging Studies

   •   USG including doppler
   •   IVP / renal scan
   •   CECT Scan – chest and abdomen
   •   MRI
   •   Others – RGP, cystoscopy




DKG /SAAPS/2008
CECT gives the anatomical details of the tumor and
    replaces IVP for assessing renal function


  DKG /SAAPS/2008
NWTS Classification of Renal tumors

Low risk - Mesoblastic Nephroma
Intermediate risk
• Favorable histology WT – Classic form of WT

High risk- Unfavorable histology
• Anaplastic (focal –diffuse)
• Clear cell sarcoma
• Rhabdoid tumor



 DKG /SAAPS/2008
    Congenital Mesoblastic Nephroma
•    Most common benign tumor ( < 6 mo age)
•    Low grade spindle cell tumor
•    Haemorrhage and necrosis,
•    Calcification rare,
•    Mostly centered near kidney hilum
•    Classical- leiomyomatous, Atypical - cellular
•    Gross- Locally invasive tumor
•    Total Surgical Excision,
•    Excellent prognosis, FU needed


    DKG /SAAPS/2008
             Clear Cell Sarcoma
   • Rare - 3% of renal tumors
   • Peaks during 2nd year
   • Bone metastasizing renal tumor
   • Higher rate of relapse and death
   • Surgery + RT + 3 drug CT
   • Poor prognosis


DKG /SAAPS/2008
                  Rhabdoid Tumor
  •   Rare tumor - 1.8% of renal tumors
  •   15% may develop brain tumors
  •   80% are stage III-IV at diagnosis
  •   Solid, bulky , well circumscribed.
  •   Extremely aggressive
  •   Metastasis in Lung in 70%
  •   Poor prognosis - 3 yr Survival <20%


DKG /SAAPS/2008
     Extra renal Wilms’ Tumor
 • Common Sites:
   Retroperitoneum
   Sacrococcygeal
   Testis, Uterus
   Inguinal canal, Mediastinum

 • Difficulty in diagnosis– histology confirms



DKG /SAAPS/2008
           Rare Lesions

• Intrarenal Neuroblastoma-
  ( Increased VMA, NSE, poor prognosis)
• Intrarenal Teratoma- Raised AFP,
  Histological diagnosis is confirmatory
• Teratoid Wilms - significant diversity of cell
  types and tissues + classic Wilms areas
  Good prognosis after excision if no yolk sac
  elements



DKG /SAAPS/2008
     Prognostic factors
1.       Stage of the disease
2.       Favorable or unfavorable histology
3.       Metastases at presentation
4.       Regional lymph node involvement
5.       Hyper-diploidy which correlates well
        with anaplastic variety




DKG /SAAPS/2008
                  NWTS Staging




DKG /SAAPS/2008
                  Histopathology

• Favorable histology
• Unfavorable histology -
3 main features of anaplasia
   a) 3-fold or greater nuclear enlargement
   b) hyperchromatism
   c) enlarged abnormal mitotic figures




DKG /SAAPS/2008
                  Aims of Treatment

• NWTS                      • SIOP
1.    Biopsy to Stratify    1. Down stage tumor by
   according to histology      Chemotherapy
2. Eliminate radiotherapy   2. No biopsy
   as far as possible       3. Only Imaging
3. Use combination          4. Treatment tailored
   chemotherapy                according to stage
4. Identify risk groups        found at surgery


Our Exp. Combination of both – imaging plus FNAC


     DKG /SAAPS/2008
                  Therapy

      •   Surgery
      •   Chemotherapy
      •   Radiotherapy
      •   Supportive therapy
      •   Managing the recurrences
      •   Special considerations for B/L WT



DKG /SAAPS/2008
       Main Surgical technique
 •   Liberal incision
 •   Radical nephrectomy Vs nephroureterectomy
 •   Clear the renal fossa
 •   Lymph node sampling
 •   Contra-lateral exploration – Just palpation
 •   Handling the pedicle
 •   Removal of thrombus
 •   Clipping the tumor bed




DKG /SAAPS/2008
       Neo-adjuvant chemotherapy
         for unresectable tumors

  • Bilateral Wilms’ tumor
  • Bulky tumors
  • Inoperable tumor
  • Intravascular supra-hepatic ext. in IVC
  • Tumor in solitary kidney




DKG /SAAPS/2008
 Treatment according to the stage
• Stage I + Favorable histology Stage II Nephrectomy
  + LN sampling + 18 weeks CT with vincristine and
  pulse-intensive dactinomycin.
• Stage II Focal anaplasia
  Nephrectomy + LN sampling + abdominal RT + 24
  weeks CT with vincristine, doxorubicin, and pulse-
  intensive dactinomycin.
• Stage II Diffuse anaplasia
  Nephrectomy + LN sampling + abdominal RT + 24
  weeks CT with vincristine, doxorubicin, etoposide,
  cyclophosphamide, and Mesna.




 DKG /SAAPS/2008
•    Stage III Wilms' Tumor
    Favorable histology and Focal anaplasia -
    Nephrectomy + LN sampling + abdominal RT
    + 24 weeks CT with vincristine, doxorubicin,
    and pulse-intensive dactinomycin.
    Diffuse anaplasia –
    Nephrectomy + LN sampling + abdominal RT +
    24 weeks CT with vincristine, doxorubicin,
    etoposide, cyclophosphamide, and mesna.




    DKG /SAAPS/2008
• Stage IV Wilms' Tumor
 Favorable histology and Focal anaplasia -
 Nephrectomy + LN sampling , abdominal RT according
 to local stage, pulmonary RT for pulm. metastases, and
 24 weeks of CT with vincristine, doxorubicin, and pulse-
 intensive dactinomycin.
 Diffuse anaplasia - Nephrectomy + LN sampling ,
 abdominal irradiation,whole-lung irradiation for
 pulmonary metastases, and 24 weeks of CT with
 vincristine, doxorubicin, etoposide, cyclophosphamide
 and mesna




DKG /SAAPS/2008
Stage V Wilms' Tumor (Bilateral tumors)
   Aim: preserve renal tissue, more CT, Less RT

• Earlier, unilateral nephrectomy + contralateral biopsy or
  heminephrectomy -> late renal failure.
• No difference in survival between initial bilateral biopsy
  -> CT -> surgical resection & initial resection -> CT.
• Preserve renal mass, minimize late renal failure.
  Bilateral biopsies + LN sampling.
  Preop CT -> second look, reassess at 6 wks with
  abdominal CT. If no reduction -> second look surgical
  procedure




  DKG /SAAPS/2008
• small synchronous bilateral polar lesions -> bilateral
  partial nephrectomies or wedge resections
• Excisional biopsy/partial nephrectomy if radical resection
  not compromised, negative margins obtained and 2/3
  renal parenchyma preserved
• Large tumor on one side and contralateral small -> radical
  tumornephrectomy on more involved side and partial
  nephrectomy on opposite.
• If not favorable for surgical intervention -> biopsy. More
  aggressive CT &/or RT. Third look
• Bilateral nephrectomy -> renal transplantation




    DKG /SAAPS/2008
 Case - Bilateral Wilms Tumor
•   Presented with bilateral renal lumps.
•   Received 4 week chemotherapy
•   Tumors reduced significantly on repeat CT
•   Planned for excision of tumors
•   December 2002: B/L Tumorectomy done
•   Biopsies showed FH, edges free of tumor




DKG /SAAPS/2008
  (B/L Wilms’ tumor) Left sided larger tumor
Much reduced with preop. 4 week chemotherapy

 DKG /SAAPS/2008
Tumor excision marked with diathermy



DKG /SAAPS/2008
  Tumor extending      Tumor excision completed,
 upto central calyx.    No clamping of Pedicle.

DKG /SAAPS/2008
   Left Tumor excision     Right renal Tumor
        completed          excision completed
    and floor sutured    and renal floor sutured.


DKG /SAAPS/2008
                  Indications of RT

    1. Stage II,III,IV with unfavorable histology
   2. Stage III & IV with favorable histology
    3. Metastatic disease
   4. CCSK, in all stages




DKG /SAAPS/2008
    Intravascular tumor extension
• USG – for thrombus and caval flow
• Neoadjuvant chemotherapy helpful.
•   Infradiaphragmatic infrahepatic adherent caval vein
    - usually disappears on chemotherapy
    - Removal of thrombus by cavotomy or Fogarty catheter
    - Excision of segment of IVC – ensure collaterals
•   Intravascular suprahepatic extension - preoperative
    chemotherapy -> decrease in size of thrombus or complete
    regression
•   Adverse, embolectomy under cardiopulm. bypass




    DKG /SAAPS/2008
              Post chemotherapy
        Renal vein with calcified tumor
            which extended in IVC




Ashu- 3 yrs with large R tumor
Received Pre-op chemotherapy for large tumor extending in IVC for
Stage III - Responded very well to CT
Was found to have resectable tumor with calcified thrombus in IVC.
Doppler US showed some lumen in IVC


 DKG /SAAPS/2008
Tumor bleed - Operated in Emergency




 DKG /SAAPS/2008
       Parenchymal sparing surgery
  ( Partial nephrectomy or tumor Enucleation )
                 we do not prefer

Criteria :                            Indications:
a. Polar tumor < 1/3 kidney       •   Localised small WT
b. Normal remaining kidney
                                  •   Bilateral WT
c. No extension into collecting
system, renal vein                •   Renal insufficiency
d. Clear demarcation between      •   Solitary kidney WT
tumor and kidney and adjacent     •   Syndromes with
structures
                                       nephrogenic rests



  DKG /SAAPS/2008
               Inoperable tumors
• Tumors with suprahepatic extension or massive
  size-> biopsied/ FNAC -> preoperative CT.
• Rarely, extension into liver -> wedge resection
  en bloc or hepatic lobectomy.
• Diaphragm infiltrated -> partial excision en bloc
• Unresectable tumor on imaging = treated as
  stage III, CT -3 drugs, if no reduction then RT.
• Surgery after sufficient tumor shrinkage (6
  wks). Treated as stage III including postop. RT.


  DKG /SAAPS/2008
                  Lung metastases

•   Chest X Ray
•   CT- more sensitive
•   Multiple – Radiation
•   If a small chest
    nodule - Confirm
    before giving whole
    lung radiation
    (NWTS-5)


DKG /SAAPS/2008
Recurrent Wilms' Tumor – our exp.
•   Risk factors associated with relapse
•   unfavorable histology,
•   LN positive,
•   > 6 yrs age,
•   diffuse spill,
•   capsular and vascular invasion, and
•   aneuploidy



DKG /SAAPS/2008
  Recurrence of Wilms tumors
        Poor prognostic factors
• Anaplastic/unfavorable histology
• Recurrence in abdomen after RT
• Recurrence within 6 months of nephrectomy
• Recurrence after initial 3-drug therapy
 (2-year survival after local recurrence - 43%)




DKG /SAAPS/2008
      Recurrent Wilms' Tumor

Further treatment depends on
• site of recurrence
• Tumor histology
• length of initial remission
• initial Chemo regimen (2 vs 3 drugs).




DKG /SAAPS/2008
         Treatment options for
              Recurrence
• Ifosfamide + etoposide + carboplatin
• High-dose CT , then autologous BM in past
• Salvage induction regimen of
   cyclophosphamide and etoposide (CE)
   alternating with carboplatin and etoposide
   (PE) – followed by delayed surgery




DKG /SAAPS/2008
AIIMS Exp. - 202 cases in 17 years
                  Cases   5- year
                  (%)     Survival
                          Rate(%)


    Stage I       19.3    95

    Stage II      15.8    95

    Stage III     43      75

    Stage IV      15.3    62

    Stage V       6.4     40


DKG /SAAPS/2008
      Long-term complications
      •   Renal failure
      •   Lung damage
      •   Congestive heart failure
      •   Liver damage
      •   Infertility - Problem to get married
      •   Second malignant neoplasm
      •   Musculoskeletal defects




DKG /SAAPS/2008
Challenges in developing countries
•   Poverty, malnutrition, ignorance
•   Presentation in advanced stages
•   Limited facilities
•   Huge tumors
•   Advanced Stage 3-5 ( 65% cases )
•   Non-compliance with schedules
•   Huge population with large volume
•   Economic reasons for poor follow-up




DKG /SAAPS/2008
DKG /SAAPS/2008
            Age at presentation
  • Bilateral tumors in 4% to 8%.
  • Median age at diagnosis for Unilateral;
    41.5 months - males
    46.9 months -females.
  • Median age at diagnosis for B/L tumors
    29.5 months- males 32.6 months –females.
  • M: F- 0.92 (unilateral) M: F- 0.6 (bilateral)
  • Most present < 5 years.



DKG /SAAPS/2008
Assoc anomalies (10 to 13% )
• Aniridia 10%
• Hemihypertrophy 2% to 3%.
• Genitourinary 5%
    (UDT, hypospadias, duplex system or fused kidney)
• Denys-Drash Syndrome WT + MPH +AGN
• WAGR Syndrome WT + Aniridia +GU + MR
• Beckwith Wiedemann syndrome
•   Macrosomia + hemihypertrophy + macroglossia
• Hemihypertrophy.



DKG /SAAPS/2008
             Molecular Biology
• Nephrogenic rests - 30 to 40%
• Loss of heterozygosity on chromosome 11p - 40%
• Wilms' tumor gene-1, 11p13 Denys-Drash syndrome.
• Wilms' tumor gene-II, 11p15 Beckwith-Wiedemann
•   p53 tumor suppressor gene
•   Diploid and aneuploid- better long-term survival




DKG /SAAPS/2008
           Clinical Presentation

•   Flank mass
•   With Secondary
•   Associated (gross /microscopic) hematuria,
•   Fever and malaise,
•   weight loss, anemia, or hypertension.




DKG /SAAPS/2008