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