MANAGEMENT OF ABDOMINAL MASSES
IN CHILDREN
Gian Battista Parigi
Chirurgia PediatricaUniversità degli Studi di Pavia
e IRCCS Policlinico "S.Matteo", Pavia
Two fundamentalconcepts:
Abdominal masses are almost always silent, therefore they must besought for…
…mostly because in almosthalf of cases they are malignant
Children’s tumours vs adults’ tumours
Epidemiologic: rare pathology (<5% of all tumours)Importance of all series reports also if scanty
Hystologic: sarcomas and embryomas >>> carcinomasMore severe aggressiveness of the tumour
Therapeutic: >>> sensibility to radiochemotherapyCurative and not merely palliative attitude
Prognostic: RFS >2yrs = “cure”Relapses / metastases immediately evident
are different from different points of view:
Management of a child with abdominalmass
General overviewClinical pictureDiagnostic work-upPrinciples of therapy
Management of a child with abdominalmass
General overviewClinical pictureDiagnostic work-upPrinciples of therapy
How we define an abdominal mass (AM) ?Circumscribed mass coming out from an
abdominal organ or districtThe definition doesn’t include generalizedabdominal distensions (intestinal occlusions,Hirschsprung disease, fecaloma, etc.) Excluded also hepatosplenomegalies from a medical cause
Management of a child with abdominalmass
General overviewClinical pictureDiagnostic work-upPrinciples of therapy
Some epidemiology data
359 AM admitted in 25 years
35.000 admissions
About 1% of the total
1,2 cases x month
Subdivision by nature
MalformationsNeoplasms
BenignMalignant
Subdivision by nature
Malignant46%
Benign17%
Not neopl.37%
Subdivision by location
IntraperitonealRetroperitoneal
Urinary tractNot Urinary
Subdivisione by location
Intraperitoneal34%
Retroperitoneal24%
Urinary42%
Wilms16% hydronephrosis
11%
other kidney 16%
other retroperiton.
7%neuroblastoma
17%
gastrointestinal app.
8%
female genital app.12%
liver &bile ducts
9%
other intraperitoneal
5%URINARY
RETROPERITONEAL
INTRAPERITONEAL
Incidence peak by age and type of cancer
Possible causes of AMA. Masse RetroperitonealiA.1. Urinarie A.1.1. Benigne / non neopl.· Idronefrosi · Cisti gigante del rene · Rene policistico infantile· Cisti multiloculare del rene· Pionefrosi· Nefroma mesoblastico· Leiomioma/Linfangioma· Angiomiolipoma· Infarto renale· Rene ectopicoA.1.2. Maligne· Tumore di Wilms· Nefroblastomatosi bilaterale· IpernefromaA.2. Non UrinarieA.2.1. Benigne / non neopl.· Ganglioneuroma· Teratoma· Linfangioma cistico· Fibrosi retroperitoneale· Ematoma surrene· Xantogranuloma
A.2.2. Maligne· Neuroblastoma· Feocromocitoma· Rabdomiosarcoma· Adenocarcinoma surrene· Lipoma e liposarcoma
B. Masse IntraperitonealiB.1. Quadranti superiori B.1.1. Benigne / non neopl.· Cisti del coledoco· Idrope colecisti· Teratoma gastrico · Emangioma / amartoma epatico· Cisti/pseudocisti pancreas· Cisti/pseudocisti milza· Tricobezoar gastricoB.1.2. Maligne:· Epatoblastoma· Metastasi epatiche· Linfoma gastrico· Pancreatoblastoma
B.2. Quadranti inferiori B.2.1. Benigne· Cisti ovaio· Teratoma ovaio· Globo vescicaleda ostruzione uretraleda difetti neurologicida ureterocele· Idrometrocolpo· Cisti dell'uraco· Aneurisma aortaB.2.2. Maligne:· Tumori ovarici· Rabdomiosarcoma GUB.3. Intero addomeB.3.1. Benigne / non neopl.· Duplicazione intestinale · Cisti mesenterica· Cisti omentale· Pseudotumore infiammatorio· Linfadenite mesenterica TBC· Milza vaganteB.3.2. Maligne· Linfomi Hodgkin /non H.· Adenocarcinoma intestinale· Tumore desmoplastico
Retroperitoneal / urinary masses
Benign /not neopl.
Hydronephrosis
Malignant
Wilms’ tumour
Hydronephrosis
Causes of hydronephrosisTorsion of the ureter
Polar vessel
Causes of hydro-
nephrosis
Ureteral kinking
Retroperitoneal masses – not urinary
Benign / not neopl.
Ganglioneuroma
Malignant
Neuroblastoma
Intraperitoneal masses – upper half
Benign / not neopl.
Gastric teratomaHepatichaemangioma / amartomaPancreatic cyst / pseudocyst
Malignant
HepatoblastomaLiver metastases
Intraperitoneal masses – lower halfBenign / not neopl.
Ovary (cyst, teratoma) Bladder globusHydrometrocolpos
Malignant
Ovary (tumors)GenitourinaryRhabdomiosarcoma
Intraperitoneal masses –whole abdomen
Benign / not neopl.
IntestinalduplicationsMesenteric cystOmental cystWandering spleen
Malignant
Hodgkin / not H.lymphomas
Why these tumours develop ?
Oncogenes
Antioncogenes
Apoptosis
Kariotype of a child with Wilms’ tumour
BilateralWilms’ tumour
in a girl withsyndrome of
Beckwith-Wiedemann
Environmentalfactors ?
Huge bilateral Wilms’ tumour
Management of a child with abdominalmass
General overviewClinical pictureDiagnostic work-upPrinciples of therapy
Prenatal diagnosis
Cyst of the ovary
Neuroblastoma
Wilms’ tumour
History data
Peritoneal cavityPainAlteration in the abdominal profile
History data
Pelvis compression symptomsNO ovarian cysts dislocation in the abdomen
The last famous words…
“The girl is a bit dumpy…”Right Wilms’ tumour 2,3 Kg
“A huge fecaloma is present…”(US scan – for > 15 months)
Retroperitoneal neuroblastoma 1,5 Kg.
Warning symptoms (1)
hematuria, hemihypertrophy, genitourinary anomalies, aniridia WTparaparesis of the lower limbs NRB with extension into the medullary canal bluish subcutaneous nodules metastasisof NRB Jaundice choledochal cyst
Warning symptoms (2)
virilizing syndrome / Cushing adrenal adenocarcinoma precocious puberty / hirsutism secreting ovarian tumorsintussusception lymphomadysuria, urinary globe bladder RMS
Warning symptoms (3)Metastatic retroorbital localisations
Clinical presentation
General criteria for a diagnosis:
Sex ( ? )Age ( ! )
Types of AM by sex
49,8
8,8
41,4
Maligni
BenignI
Non neopl
42,6
24,8
32,6
males
female
Types of AM by age
32,6
17,8
49,6
68,6
8,5
22,9
37,3
25,4
37,3
0%10%20%30%40%50%60%70%80%90%
100%
< 1 anno 1-5 anni > 5 anni
Maligni Benigni Non neopl.
Clinicalpresentation
CarefulinspectionGentlepalpation
What to appreciate with palpation ?
MobilityFixed retroperitoneal massesMovable intraperitonealmassesMovable with inspirationliver masses
What to appreciate with palpation ?
Location crossing the midline =
neuroblastomaNot crossing = WilmsLUQ spleen not always !RUQ liver what ?
Wilms
neuroblastoma
What to appreciate with palpation ?
Location crossing the midline =
neuroblastomaNot crossing = WilmsLUQ spleen not always !RUQ liver what ?
What to appreciate with palpation ?
Increasedpain
Torsion of an ovarycyst
Management of a child with abdominalmass
General overviewClinical pictureDiagnostic work-upPrinciples of therapy
Laboratory exams
Neoplastic markers :aspecific: ferritine, LDH, CEAsusp. NRB: urina VMA & HVA, serum NSE susp.ovarian tumour: CA-125, b-HCGsusp.teratoma or liver tumour: a-FP, b-HCG
Diagnostic imagingDetermine the anatomical compartmentIdentify the organ of originDetermine the consistency of the massAssess the degree of invasion of adjacent organs and structuresDetermine the presence of calcifications ( NRB )Determine the presence of distant metastatic lesions
Methods of imaging
UltrasoundRx abdomen plain and with contrast
TCRMNDigitaslised angiography
Nuclear medicinePET / PET-TC
Ultrasound
Plain abdomen Rx
Standard contrast Rx
TC
Magnetic Resonance Imaging
Bone scintiscan
total body MIBG scintiscan
Laparoscopy
Diagnostic option
Therapeutic option
Management of a child with abdominalmass
General overviewClinical pictureDiagnostic work-upPrinciples of therapy
Not neoplastic AM
Neoplastic benign AM
How can we treat these tumours ?
ChemotherapyRadiotherapy
Surgery
TailoringProtocols
Neuroblastoma: survival w/wo ABMT
Neoplastic malignant AM
Radical surgeryTo completely remove the mass
Conservative surgeryNot to mutilate child’s physicalentirety
The role of surgeryDemolitive surgery ?
Extended sacrifice of the organs
Aggressive surgery ?Subadventitial resection of the tumour
“Intermediate” surgery ?Removal of tumour and lymphnodes
Conservative surgery ?Biopsy for histology and biology studies
Aggressive surgery
stomach
spleenNEUROBLASTOMA
Left kidney
“Intermediate surgery” : tumour / l.nodes removal
Conservative surgery – biopsy
Antiadhesions
gel
Demolitive surgery
Conservative surgery
Long-term sequelae to the treatment
Left kidney“disappeared”after radiotherapyfor leftadrenal NRB
There is no more space for soloists …
…but for an harmonious orchestra
Giving ample space for new players to integrate in the complex
Immunologist
ImmunotherapyBrenda L. Soto, Jacquelyn A. Hank et al. The anti-tumor effect of resveratrol alone or in combination with immunotherapy in a neuroblastoma modelCancer Immunol Immunother. 2011 May; 60(5): 731–738.
ImmunotherapyResveratrole (3,5,4'-trihydroxy-trans-stilbene) natural phenol produced by plants when attacked by pathogens Peritumoral infusion of resveratrol in combination with i.v. immunocitochine in vivo in mice with neuroblastomaPrimary tumor regressed in all mice treatedwith peritumoral resveratrol
Geneticist
11p13 deletionin a boy
withWAGR
syndrome
W = WilmsA = Aniridia
G = GenitourinaryR = mental Retardation
WAGR syndrome
GenomicL.Chesler, W.A. WeissGenetically engineered murine models (GEMM) – Contribution to our understanding of the genetics, molecular pathology and therapeutic targeting of neuroblastomaSemin Cancer Biol. 2011 October; 21(4): 245–255.
GenomicRelationship between pediatric cancer and abnormal development processes
Genetic simplicity in relation to adult cancers
New advances in GEMM technology
Model TH - MYCN GEMM used for a varietyof molecular-genetic applications and development of preclinical applications
Nanopharmacologist
Laboratory of nanopharmacology
Luigi Manzo
Università di PaviaIRCCS Fondazione Salvatore Maugeri
Enhanced Delivery of Active Agents toSolid Tumors Using Nanoparticles
Enhanced permeability and retention (EPR) effect. After intravenous injection, nanoparticles accumulate in tumors through leaky and permeable tumor vasculature and impaired lymphatic system. Dong and Mumper, Nanomedicine 2010.
Drug Property Modulation in a Multi-Functional Nanoplatform
Combined modalities for targeting, imaging, stealth coating and monitoring of cancer diagnosis and safe/effective treatment.
Off-targetorgan toxicity
inhibitor
NanopharmacologyPuiyan Lee,1 Ruizhong Zhang,1 Vincent Li,1 et al
Enhancement of anticancer efficacy using modified lipophilic nanoparticle drug encapsulationInt J Nanomedicine. 2012; 7: 731–737.
NanopharmacologyGold porphyrin or camptothecin (inhibitor of DNA topoisomerase I) encapsulated and tested in vivo model of neuroblastoma N2AIncreased specific uptake in tumor tissue
increased antineoplastic effectivenessIncreased efficiency of the drug release in tumor tissue
NanogenomicsDaniela Di Paolo, Chiara Brignole, Fabio Pastorino et al. – Gaslini Hospital
Neuroblastoma-targeted
Nanoparticles Entrapping siRNA
Specifically Knockdown ALKMol Ther. 2011 June; 19(6): 1131–1140.
NanogenomicsAnaplastic lymphoma kinase (ALK) increases cellular growth and progression of NRB Anti-GD2-targeted nanoparticles carrying ALK-direct siRNA, specifically released in NRB cells expressing GD2I.V. injection of lyposomes marked with ALK-siRNA specific antineoplasticactivity without collateral effects