U.O. Clinicizzata di Chirurgia Pediatrica – P.O. di Pescara

Cattedra di Chirurgia Pediatrica – Università di Chieti-Pescara

Professore Pierluigi Lelli Chiesa

RUOLO DELLA CHIRURGIA NEI LINFOMI

ADDOMINALI / INTESTINALI

P. Lelli Chiesa, G. Lauriti

Pediatric Gastrointestinal Tumors, Murphy JT and Foglia RP,

in Pediatric Surgery 7th edition , 2012

EPIDEMIOLOGIA

Lymphoma is the most common small bowel malignancy in children, with

high-grade non-Hodgkin lymphoma (NHL) comprising 74% of these tumors.

Burkitt lymphoma constitutes the most common histologic subtype. The

majority of patients (50% to 93%) present with lymphoma localized to the

distal small bowel, although tumor may occur anywhere from the stomach

to the rectum.

GASTROINTESTINAL TUMORS

Gastrointestinal tumors in children and adolescents, Ladd AP and Grosfeld JL, Sem Ped Surg 2006

Non-Hodgkin’s lymphoma (NHL) remains the most common malignancy of

the GI tract in children.

Non-Hodgkin’s Lymphoma

• 3a più frequente neoplasia in età pediatrica

• 3 sottotipi istologici:

- 65% Non-Hodgkin’s lymphoma (NHL) a cellule B

linfoma di Burkitt

linfoma diffuso a grandi cellule B

- 20% Linfoma linfoblastico

- 15% Linfoma anaplastico a grandi cellule

Il Linfoma di Burkitt da solo rappresenta il 40-50% dei NHL pediatrici.

Site distribution of lymphomas

Kohno S et al,

Histopathology 2003

Primary gastrointestinal tract lymphoma in the

pediatric patient: review of 265 patients from the

SEER registry. Kassir N et al, J Pediatr Surg 2011

St Jude’s staging system for Burkitt lymphoma

Clinical implications and surgical management of intussusception in pediatric patients with Burkitt lymphoma,

Gupta H et al, J Pediatr Surg 2007

Stage I A single tumor (extranodal) or involvement of a single anatomical area(nodal), with the exclusion of the mediastinum and abdomen.

Stage II A single tumor (extranodal) with regional node involvement.Two or more nodal areas on the same side of diaphragm.Two single extra nodal tumors, with or without regional node involvementon the same side of the diaphragm.A primary gastrointestinal tract tumor (usually in the ileocecal area), withor without involvement of associated mesenteric nodes, that iscompletely resectable.

Stage III Two single tumors (extranodal) on opposite sides of diaphragm.Two or more nodal areas above and below the diaphragm.Any primary intrathoracic tumor (mediastinal, pleural, or thymic).Extensive primary intraabdominal disease.Any paraspinal or epidural tumor, whether or not other sites are involved.

Stage IV Any of the above findings with initial involvement of the central nervoussystem, bone marrow, or both.

The very rapid growth of this lesion gives us a clue about

the diagnosis. Burkitt’s lymphoma has the shortest

doubling time of cancers in humans and thus was our

leading diagnosis.Case 11-2013: A 4-Year-Old Boy with Fever and

Abdominal Pain. Ryan DP et al, N Engl J Med 2013

BURKITT’S LYMPHOMA

La rapidità del raddoppio volumetrico di questa neoplasia porta

frequentemente a una presentazione di addome acuto che può

essere confusa con altre malattie (occlusione intestinale secondaria

ad invaginazione ileo-cecale causata dalla crescita tumorale,

occlusione intestinale o sanguinamento; alcuni casi possono esordire

con un quadro simile all’appendicite acuta).

Primary gastrointestinal tract lymphoma in the pediatric patient: review of 265 patients from the

SEER registry. Kassir N et al, J Pediatr Surg 2011

• The most common complaint is abdominal pain that has

been present for several weeks before diagnosis

• Weight loss occurs in nearly half of patients and nausea

and vomiting are common

• A palpable mass is found in one third of cases

• Those children that present with colicky abdominal pain

and heme positive stools may have intussusception from

an intramural mass in the distal ileum or cecum

• Fever is seen in 26% of children and an initial diagnosis of

appendicitis may be made

PRESENTAZIONE CLINICA

Lymphoma, Billmire D.F., in The Surgery of Childhood Tumors 2nd edition, 2008

The role of surgery in abdominal non-Hodgkin's lymphoma: experience from the

Childrens Cancer Study Group. LaQuaglia MP et al, J Pediatr Surg 1992

The multicenter Children’s Cancer Study Group experience revealed a

similar pattern with correct preoperative diagnosis in 15% of patients.

In this series, more than half of children had an urgent operation and

most of those were felt to have appendicitis or intussusception.

Casistica 1962-2005

189 Burkitt addominali

33 invaginazionietà media 10aa

23pts (70%) limited stage II

156 altri

10pts (6.4%) stage II

Clinical implications and surgical management of intussusception in

pediatric patients with Burkitt lymphoma

Gupta H et al, St Jude Children’s Research Hospital, Memphis, USA

J Pediatr Surg 2007

Wayne et al [J Pediatr Surg 1976] reported a series of 378

patients with intussusception; only 12 patients were older than 6

years, and 6 of these 12 patients had lymphosarcoma

(lymphoma).

Therefore, they recommended that in children older than 6 years, even if

hydrostatic reduction is done, extensive small bowel reflux should be observed and an

upper gastrointestinal series performed after the evacuation of barium to rule out any

pathologic lead points.

However, it is generally believed that intussusception caused by lymphomas is unlikely to

be completely reduced by an air-contrast or barium enema.

Intussusception - Lymphoma

Clinical implications and surgical management of intussusception in pediatric patients with Burkitt lymphoma,

Gupta H et al, J Pediatr Surg 2007

Surgical approach to intussusception in older children: Influence of lead points, Banapour P et al,

J Pediatr Surg 2015

Intussusception

Children older than 5 years are much more likely to have a pathologic

lead point and early surgical intervention should be considered. Enema

reduction was safe but minimally beneficial in this age group.

Intussusception

244 children with intussusception, median age 8.2mm (range 16dd-12.7yy)

Current success in the treatment of intussusception in children, Kaiser AD et al, Surgery 2007

Caso clinico 1 – C.F.

• 2 anni e 4 mesi, maschio, da circa 10 giorni coliche addominali ricorrenti,

episodi di vomito anche biliare, alvo tendenzialmente stitico (evacuazione di feci

abbondanti, gommose e di odore fetido dopo clisteri evacuativi), irritabilità,

inappetenza e perdita di peso

• Eco Addome c/o altra sede: sospetta invaginazione intestinale clinicamente

intermittente con immagine ecografica fissa da 48 ore (“in fianco-ipocondrio dx

persistenza di ansa intestinale di pertinenza colica, con aspetto “a bersaglio” con

Ø trasversale di 3.5cm ad estensione cranio-caudale di 7cm”)

• Trasferito c/o la nostra U.O.C.. Eco Addome: a livello della flessura colica

destra ansa intestinale fissa con immagine a coccarda tipica di invaginazione

intestinale; in corrispondenza della testa dell’invaginato si rileva un’immagine

rotondeggiante di circa 3x2.5cm, ad eco struttura omogeneamente fine.”

• Rx clisma opaco: non risoluzione dell’invaginazione

Caso clinico 1 – C.F.

LAPAROSCOPIA ESPLORATIVA?

Invaginazione ileo-ceco-colica secondaria a neoformazione della valvola ileo-cecale:

exeresi dell’intestino invaginato ed anastomosi ileo-colica termino-terminale

extramucosa.

Diagnosi di Linfoma di Burkitt, stadio Il sec. Murphy.

Trattamento chemioterapico sec. protocollo AIEOP-LNH97.

Caso clinico 1 – C.F.

Quadro istopatologico a “cielo stellato” (starry sky), tipico del Linfoma di Burkitt

Caso clinico 2 – R.C.

• 11 mesi di età, femmina, circa 15 giorni prima episodio di gastroenterite

autolimitatosi. Da >24 ore la piccola ha iniziato ad accusare crisi di pianto

inconsolabile con flessione delle gambe e cosce sull’addome, intervallati da

episodi di sonno e prostrazione, alternati a nuove crisi di pianto. Comparsa di

vomito alimentare e successivamente evacuazione di feci miste a muco e sangue

• La paziente giunge c/o la nostra U.O.C.. Riscontro di materiale muco ematico al

sondaggio rettale

• Rx clisma opaco: “regolare risalita del mdc fino al colon ascendente ove si

osserva interruzione del lume. Dopo ripetuti tentativi: parziale opacizzazione del

cieco che appare dismorfico, con visualizzazione dell’appendice. Reperti riferibili

verosimilmente ad invaginazione con successiva parziale ricanalizzazione del

colon. Non opacizzata l’ultima ansa ileale.”

Caso clinico 2 – R.C.

Laparotomia (ore 2am) Invaginazione ileo-ceco-colica secondaria a

neoformazione polipoide sessile della valvola ileo-cecale: exeresi

dell’intestino invaginato ed anastomosi ileo-colica termino-terminale

extramucosa.

Diagnosi: iperplasia follicolare linfoide reattiva ileo-colica, appendicolare e

linfonodale – prevalente a carico della mucosa cecale e della valvola ileo-

cecale – associata a flogosi erosiva e ad aspetti rigenerativi dell’epitelio

ghiandolare.

Surgery at 3am

D.M. Hays (Los Angeles, CA): I would like you to visualize

yourself in the operating room at 3am with an intussusception

that can't be reduced by hydrostatic pressure and the question

comes up as to what it is. Is it an irreducible intussusception, is it

really a tumor, how do you make this distinction? Do you do

biopsies? Can you tell right away? How do you handle it?

M.P. LaQuaglia (response): I can't be definitive about I think that

many of these patients are going to present urgently and that

you just have to rely on surgical judgment. It may be that you will

have to do a sleeve resection. The only caveat, you can't do

cytogenetics and immunophenotyping on formalin tissue so that

some awareness of the possibility that an appendicitis,

intussusception, or bowel perforation may be a lymphoma may

be helpful in term of getting some of the tissue stored in the

refrigerator so that the more esoteric studies can be done.

The role of surgery in abdominal non-Hodgkin's lymphoma: experience from the Childrens

Cancer Study Group. LaQuaglia MP et al, J Pediatr Surg 1992

Paziente di 14 anni, maschio, da circa 24 ore vomito alimentare e quindi biliare

associato ad intenso e continuo dolore addominale, diffuso a tutti i quadranti ma

più accentuato in fossa iliaca destra, associato ad alvo chiuso alle feci da 5

giorni. Rx Diretta Addome: multipli livelli idro-aerei.

Caso clinico 3 – D. P. G.

Occlusione intestinale da stenosi ileale (a circa 30cm dalla valvola ileo-cecale):

resezione di circa 10cm di ileo ed anastomosi ileo-ileale termino-terminale

extramucosa.

Diagnosi: Linfoma di derivazione dai linfociti B periferici, a grandi cellule diffuso

a fenotipo GC-like (centro germinativo) a localizzazione ileale, II stadio sec

Murphy. In trattamento sec. Protocollo AIEOP LNH B 97, R2.

Caso clinico 3 – D. P. G.

The surgeon’s approach to non-Hodgkin’s

lymphoma in the abdomen will be dictated by the

clinical scenario and anatomic findings.

Approximately half of the cases will involve the

gastrointestinal tract and the vast majority of those

will arise in the distal ileum or the right colon.

Most of the gastrointestinal lymphomas will present

as an acute abdomen due to tenderness or

obstruction and many are focal lesions that are

amenable to straightforward resection with

anastomosis.

RUOLO DELLA CHIRURGIA

Lymphoma, Billmire D.F., in The Surgery of Childhood Tumors 2nd edition, 2008

Surgical intervention is focused on either complete resection or palliative

intervention for the relief of bowel obstruction, in addition to a definitive

tumor biopsy.

Frozen section analysis of unexpected tumors should be obtained

intraoperatively to make a correct diagnosis and determine appropriate

therapy.

The mainstay of treatment for isolated gastrointestinal lymphoma is

complete surgical resection when possible, including excision of regional

lymph nodes.

Nearly 50% of children with gastrointestinal NHL will have tumor infiltrates

confined to the gastrointestinal tract with possible regional lymph node

involvement.

Children that are amenable to localized resection have an 80% survival at

2 years. Those children with more extensive spread of disease have a 33%

2-year survival.

RUOLO DELLA CHIRURGIA

Gastrointestinal tumors in children and adolescents, Ladd AP and Grosfeld JL, Sem Ped Surg 2006

?

Clinical implications and surgical management of

intussusception in pediatric patients with Burkitt lymphoma.

Gupta H et al, St Jude Children’s Research Hospital, Memphis, USA, J Pediatr Surg 2007

Today, almost all patients with stage II disease and over 80% of those with

stage III or IV disease can be cured with chemotherapy. Complete resection of

the tumor would allow less intensive therapy and improve quality of life of the

survivors.

Complete tumor resection with minimal complication is possible in most patients who

present with intussusception; thus, their stage of disease can be downgraded to

stage II.

Importantly, the surgeon should thoroughly explore all the peritoneal surfaces, collect

ascitic fluid, and examine liver, spleen, and retroperitoneal nodes. The presence of

residual disease indicates that the patient has stage III disease and requires a much

more intense chemotherapy regimen for cure.

If extensive disease is noted in the abdomen such that complete resection is not

feasible, biopsy alone should be done.

Aggressive surgical resection should be avoided in cases of advanced disease,

because this approach not only would fail to completely resect the disease, but could

increase the risk of surgical complications and delay the start of curative

chemotherapy.

Primary gastrointestinal tract lymphoma in the pediatric patient: review of 265 patients

from the SEER registry. Kassir N et al, J Pediatr Surg 2011

RUOLO DELLA CHIRURGIA NEI LINFOMI

GASTRONTESTINALI PEDIATRICI

RUOLO DELLA CHIRURGIA NEI LINFOMI

GASTRONTESTINALI PEDIATRICI

In our evaluation of the 265 pediatric patients in the SEER

(Surveillance, Epidemiology and End Result) database from 1973 to

2006, by univariate analysis, surgery did not improve long-term

survival but was found to significantly decrease 10-year overall

and DSS in patients 10 years or older. There was no difference in

overall or DSS for those younger than 10 years who underwent

surgical extirpation.

Primary gastrointestinal tract lymphoma in the pediatric patient: review of 265 patients

from the SEER registry. Kassir N et al, J Pediatr Surg 2011

Without question, urgent surgery is required in patients with primary

GI tract lymphomas who develop obstruction or perforation of the

alimentary tract. However, in cases where these clinical findings are not

present, arguments against the use of surgery have been largely based on

the rate of surgical complications requiring prolonged hospitalizations and

leading to delays in the initiation of chemotherapy.

Burkitt lymphoma

Bowel Obstruction after Treatment of Intra-Abdominal Tumors, Aguayo P et al,

Eur J Pediatr Surg 2010

In the patients with Burkitt’s lymphoma who underwent

an abdominal operation, the incidence of p.o. small bowel

obstruction was 17.6%. As in procedures to resect Wilm’s

tumor or rhabdomyosarcoma, operations for Burkitt’s

lymphoma are often major procedures.

Abdominal Burkitt’s Lymphoma

Diagnosis in Childhood Abdominal Burkitt’s Lymphoma, Vural S et al, Ann Surg Oncol 2010

Caso clinico 4 – A. I.

• Paziente di 4 anni, femmina, ricovero c/o la ns. UOC il 12.06 per addome

globoso e riscontro accidentale di massa addominale sinistra all’esame

ecografico (formazione solida diffusamente ipo-ecogena, Ø 10x8cm,

polilobulata con aree necrotico-emmorragiche al suo interno ed aree di

vascolarizzazione all’eco-color doppler.

• TC Addome con mdc 15.06 massa Ø 20x14cm a contenuto disomogeneo

senza calcificazioni, posta lateralmente allo stomaco dislocato verso destra,

anteriore a milza e pancreas, che si estende in basso fino allo scavo pelvico;

evidenti aree di consolidamento in sede polmonare basale bilateralmente.

• 16.06 biopsia percutanea eco-guidata con Tru-cut e posizionamento di

CVC tipo Broviac

• Diagnosi istologica: Linfoma non Hodgkin a grandi cellule B diffuso cs III,

sottoposta a trattamento sec. protocollo AIEOP LNH97 gruppo R4.

Caso clinico 4 – A. I.

• Durante il trattamento le dimensioni della lesione sono state controllate mediante Eco

addome a cadenza bisettimanali. Rivalutazione TC addome a 2 mesi (17.08):

riduzione dimensioni della massa (Ø 11x6cm), scomparsa delle aree di consolidazione

parenchimale in sede polmonare basale bilateralmente.

• Data la modesta riduzione della massa alla TC addome a 3 mesi (12.09), Ø 8x4cm, ed

alla Eco addome del 05.10 (Ø 8x5cm), si esegue second look chirurgico il 13.10:

laparotomia sovra-ombellicale trasversa sinistra, exeresi en bloc della massa tumorale

tenacemente adesa all’ilo splenico ed alla coda del pancreas, con asportazione di

piccola area della coda del pancreas e tessuto splenico polare inferiore (1cm), con

conservazione della milza.

• Esame istologico: massa diffusamente necrotica con reazione xantomatosa.

• Alla luce del quadro anatomo-patologico, non essendovi evidenza di malattia attiva, si

conviene di sottoporre la paziente ad un ultimo ciclo di chemioterapia, non sussistendo

indicazione a terapia ad alte dosi.

RUOLO DELLA CHIRURGIA NEI LINFOMI

GASTRONTESTINALI PEDIATRICI

La chirurgia gioca ancora un ruolo importante in situazioni

esattamente definite:

• resezione completa della malattia localizzata

• trattamento della malattia complicata (occlusione intestinale,

invaginazione, perforazione…)

• biopsia diagnostica *

• second look

N.B. * Va evitato qualunque intervento di chirurgia maggiore che possa portare ad

una più alta incidenza di complicanze post-operatorie e conseguentemente

ad un ritardo nell’inizio della chemioterapia.

Clinico-Pathological Features and Outcome of Management of Pediatric Gastrointestinal

Lymphoma. Morsi A et al, J Egypt Natl Canc Inst. 2005

Today, almost all patients with stage IIdisease and over 80% of those with stage IIIor IV disease can be cured withchemotherapy. Complete resection of thetumor would allow less intensive therapyand improve quality of life of the survivors.

Clinical implications and surgical management of intussusception in pediatric patients with Burkitt lymphoma.Gupta H et al, St Jude Children’s Research Hospital, Memphis, USA, J Pediatr Surg 2007

RUOLO DELLA LAPAROSCOPIA

Diagnostico

• Come tempo preliminare essenziale in ogni paziente >5-6 anni con

invaginazione non riducibile

• Per esplorare accuratamente le superfici peritoneali, collezionare liquido

ascitico ed esaminare fegato, milza e linfonodi retroperitoneali

• Per prelievi bioptici in caso di malattia estesa

• Anche come second look post-chemioterpia

Terapeutico?

“The open surgical approach is still the gold standard in most pediatric

surgical facilities.”

Ileocolic intussusception due to Burkitt lymphoma: a case report

Balanescu NR et al, J Med Life 2013