17503299

The Relevance of Surgical Therapy for Bilateral and/or Multiple Pulmonary Metastases in Children

Authors	F .- M. Häcker1, D. v. Schweinitz 1,3, F. Gambazzi2
Affiliations	1 Department of Pediatric Surgery, University Children's Hospital, Basel, Switzerland 2 Department of Thoracic Surgery, University of Basel, Basel, Switzerland 3 Department of Pediatric Surgery, Dr. von Haunersches Children's Hospital, Munich, Germany

Key words

· bilateral/multiple pulmo- nary metastases

surgery

· childhood

Mots-clés

· métastases pulmonaires bilatérales multiples

· chirurgie

· enfance

Palabras clave

· metástasis bilaterales o múltiples

· cirugía

· niños

Schlüsselwörter

· bilaterale/multiple unilate- rale Lungenmetastasen

Chirurgie

l ” Kindesalter

Abstract

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Purpose: Pulmonary surgery is frequently used for the treatment of metastases in children with various malignant diseases. The benefit of an ag- gressive surgical treatment in children with bi- lateral and/or multiple pulmonary metastases is still discussed controversially.

Methods: A retrospective analysis of 10 children (7 girls, 3 boys; age range from 2 to 16.5 years) who underwent thoracotomy for bilateral and/or multiple pulmonary metastases was performed. The primary malignancies were osteosarcoma (n=4), hepatoblastoma (n=3), malignant pe- ripheral nerve sheath tumor (n = 1), adrenocorti- cal carcinoma (n = 1) and alveolar rhabdomyosar- coma (n =1). Unilateral but multiple pulmonary metastases were found in 3 children. 7 patients showed bilateral pulmonary metastases. Preop- erative induction chemotherapy with tumor re- gression and a subsequent decrease in the size and number of pulmonary metastases was man- datory for the surgery of metastases.

Results: Standardized bilateral thoracotomy was performed in 4 patients in 1 operation (in 1 pa-

tient combined with a hemihepatectomy), and in 3 patients, in 2 operations on different days. 5 children underwent re-thoracotomy due to re- current pulmonary metastases (2 patients: uni- lateral; 3 patients: bilateral; 1 patient: twice bi- lateral). All visible and palpable metastases (1 - 25) were excised, either by wedge resection, by segment resection or by lobectomy. Postopera- tive artificial ventilation was necessary for 0 to 24 hours. Postoperative complications included intrathoracic secondary hemorrhage in 3 cases and pneumonia in 1 patient. 2 patients (20%) died of recurrent metastatic disease (osteosarco- ma: 1; adrenocortical carcinoma: 1). During a mean follow-up period of 49 months (14 to 66 months after the last thoracotomy), 8 patients (80%) remained in complete remission without clinically relevant respiratory restrictions.

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Conclusion: Complete surgical resection of pul- monary metastases after response to induction chemotherapy may increase survival in carefully selected children, even in cases with multiple and recurrent metastatic disease. In children, bi- lateral thoracotomy within a single operation is possible without an increased complication rate.

received November 4, 2005 accepted after revision December 12, 2005

Bibliography

DOI 10.1055/s-2007-964873 Eur J Pediatr Surg 2007; 17: 84-89 @ Georg Thieme Verlag KG Stuttgart . New York . ISSN 0939-7248

Correspondence

Dr. Frank-Martin Häcker Department of Pediatric Surgery University Children’s Hospital P.O. Box 4005 Basel Switzerland

frankmartin.haecker@ukbb.ch

Introduction

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The most frequent pediatric thoracic malignan- cies are pulmonary metastases secondary to solid tumors. Primary solid tumors of childhood, such as osteosarcoma (OS), hepatoblastoma (HB) and nephroblastoma, commonly spread to the lungs. Within the last 10 to 15 years, the treatment of malignant diseases in childhood has significantly improved the outcome of affected children. These improved outcomes are due to more accurate di- agnostic tools as well as more differentiated on- cologic therapy protocols including chemother- apy, radiotherapy and surgery. In cases with uni- lateral and/or solitary metastatic disease, pulmo-

nary surgery is frequently used for the treatment of metastases in children with various malignant diseases. However, the benefit of an aggressive surgical treatment in children with bilateral and/ or multiple pulmonary metastases is still dis- cussed controversially. Additionally, only little data is available on bilateral thoracotomy carried out as a single operation in children. In order to evaluate the risks and benefits of surgery for multiple unilateral and/or bilateral pulmonary metastases in children with different malignan- cies, we analyzed the data from patients who underwent thoracotomy for pulmonary metasta- ses due to primary malignancies such as HB, OS, malignant peripheral nerve sheath tumor

(MPNST), adrenocortical carcinoma (AC) or alveolar rhabdomyo- sarcoma (RMS).

Patients and Methods

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In a retrospective study, we reviewed the records of patients who underwent thoracotomy for pulmonary metastases between June 1999 and November 2004 at our institution. Data included age at diagnosis and thoracotomy, sex, primary malignancy, pri- mary therapy, interval between diagnosis and the appearance of pulmonary metastases, location, size and number of radiologi- cally detectable and resected metastases, results of histopatho- logic examination and outcome. Pulmonary metastases were de- tected by posteroanterior and lateral chest X-ray and thoracic computerized tomography (CT). The indication for thoracotomy was based on the following criteria:

No evidence of residual or recurrent primary malignancy.

No evidence of extrapulmonary metastatic disease.

Preoperative chemotherapy (ChT) with regression and a sub- sequent decrease in the number and size of pulmonary metas- tases.

· Assessment as a surgically resectable disease with no subse- quent postoperative residual disease and no postoperative re- sidual pulmonary insufficiency.

All patients underwent conventional lateral thoracotomy. Nei- ther median sternotomy nor video assisted thoracoscopic sur- gery (VATS) was performed. Selective intubation was carried out using a double lumen tube. The lung was assessed macro- scopically, and carefully palpated in both its deflated and in- flated state. The nodules were dissected sharply and excised to- gether with a 1-2 cm wide margin of apparently normal sur- rounding lung tissue. In cases of multiple metastases or centrally located metastases, segment resection or lobectomy was per- formed.

All patients were treated according to the individual GPOH (Ger- man Society of Pediatric Oncology) study protocol [3,4,6,10,11, 13,14]. Adjuvant pre- and postoperative chemotherapy and/or radiotherapy were used, depending on the primary malignancy, the histology of the metastasis and the interval between the di- agnosis of the primary malignancy and the appearance of pul- monary metastases.

Results

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From June 1999 to November 2004, 10 patients underwent thor- acotomy for bilateral and/or multiple pulmonary metastases. Primary malignancies were osteosarcoma (OS) (n =4), hepato- blastoma (HB) (n =3), malignant peripheral nerve sheath tumor (MPNST) (n=1), adrenocortical carcinoma (AC) (n=1) and alve- lolar rhabdomyosarcoma (RMS) (n= 1) (+ Table 1). The mean age at the time of diagnosis was 9.7 years (range 2-16 years). In 4 patients (40%), pulmonary metastases were encountered at the time of initial diagnosis (patients nos. 1, 6, 9 and 10). In the re- maining 6 patients, the mean time between diagnosis of the pri- mary malignancy and the appearance of pulmonary metastases was 20 months (range 4-56 months) ( Table 1). Unilateral but multiple pulmonary metastases were found in 3 children (30%). They were mostly nodular, and located in the right lung in cases of unilateral disease in 2 patients. 7 patients showed bilateral pulmonary metastases.

All patients underwent resection of the primary malignancy be- fore surgery of lung metastases except for 1 boy, in whom bilat- eral thoracotomy was done during the same procedure after hemihepatectomy. Another 3 patients underwent bilateral thor- acotomy in a single procedure. Segmentectomy (6 patients) or lobectomy (3 patients) was done when the site, size and/or num- bers of the metastatic nodules within the lung and close to the bronchus made complete removal necessary. Otherwise, exci- sion was done by means of wedge resection (1-25 nodules). The nodules contained vital tumor cells in most cases (>95%). In 5 patients, 10 re-thoracotomies were performed because of re- current metastatic lesions ( Table 1). One girl (patient no. 2) underwent a second re-thoracotomy of both lungs.

Postoperative ventilation was necessary for 0 to 24 hours. Post- operative complications included intrathoracic secondary hem- orrhage in 3 cases (patient no. 9 required re-thoracotomy for he- mostasis) and pneumonia in 1 patient. During the mean follow- up period of 49 months (14 to 66 months after the last thoracot- omy), the surviving 8 patients (80%) presented with complete remission without clinically relevant respiratory restrictions.

Details of Treatment

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Patient no. 1 presented with bilateral pulmonary metastases at the time of initial diagnosis of OS. Despite high-dose induction ChT preoperatively, the patient demonstrated an increase in the size and number of pulmonary metastatic nodules. Although all visible and palpable metastases were removed completely and ChT was continued, the girl developed bilateral recurrent meta- static disease within 5 months. After bilateral re-thoracotomy, the histopathologic evaluation again showed vital tumor tissue, and the girl died of metastatic disease 6 weeks later. The remain- ing 3 patients with OS underwent preoperative induction ChT and subsequent resection of the primary malignancy, and stayed in remission thereafter. Although repeated recurrent pulmonary metastases required a total of 4 re-thoracotomies in patient no. 2, she has demonstrated no evidence of disease for 52 months. All 3 patients with HB received preoperative ChT, with a good re- sponse of both the primary tumor and the pulmonary metasta- ses in 2 children. In patient no. 6, pulmonary metastases were encountered at the time of initial diagnosis. Therefore, bilateral thoracotomy was performed together with laparotomy during a single anesthesia after induction ChT. Despite high-dose induc- tion ChT, patient no. 5 showed no relevant response of the pri- mary tumor and developed bilateral pulmonary metastases 6- 8 months after laparotomy. An increase of the tumor marker o- fetoprotein and thoracic CT demonstrated recurrent bilateral metastatic disease 6-8 months later. After performing bilateral re-thoracotomy with removal of vital metastases, regular fol- low-up examinations have shown no evidence of disease for 59 months.

Patient no. 8, a 13-year-old girl with MPNST, underwent local re- resection of the primary malignancy three times within 54 months. The treatment was completed by pre- and postopera- tive ChT according to the CWS study protocol [6,13]. 2 months later, thoracic computerized tomography (CT) detected 3 nod- ules in the upper and middle lobe of the right lung. After right- sided thoracotomy, histopathologic evaluation demonstrated vi- tal tumor cells of the primary malignancy. 14 months later, CT showed 2 suspicious nodules in the lower lobe of the right lung. However, histopathologic evaluation revealed no vital tumor

Table 1 Patient characteristics

No.	Sex	Age (at diagnosis)	Primary malignancy	Therapy	Interval to pulmonary metastasis/ recurrence of primary tumor	Location of metastases	Nodules (number)	Type of excision	Follow- up	Outcome
1	F	13 y	osteosarcoma	preoperative ChT						DoD
			(proximal tibia r. s.)	tumor resection
				bilateral thoracotomy	0 months	UL r. s.	1 (5 cm)	s. r.
						LL r. s.	2	w. r.
						LL I. S.	1	w.r.
				re-thoracotomy r. s.	5 months (since r. s. thoracotomy)	UL r. s.	2	w.r.
						ML r. s.	2	w.r.
						LL r. s.	5	w.r.
				re-thoracotomy l. s.	5 months (since l. s. thoracotomy)	UL l. s.	3	w. r.
						LL I. S.	3	w. r.
2	F	8 y	osteosarcoma (proximal tibia r.s.)	preoperative ChT primary tumor resection					52 m	NED
				local re-resection	7 d
				thoracotomy l. s.	4 months	LL I. S.	5	w.r.
						UL I. S.	1	w.r.
				thoracotomy r. s.	5 months	LL r. s.	3	w.r.
				re-thoracotomy l. s.	7 months (since l. s. thoracotomy)	LL I. S.	2	w.r.
				expl. thoracotomy r. s.	7 months (since r. s. thoracotomy)	no mx
				re-thoracotomy r. s.	23 months (since r. s. thoracotomy)	ML r. s.	1 (5 cm)	s.r.
				re-thoracotomy r. s.	5 months (since r. s. re-thoracotomy)	UL r. s.	1 (3 cm)	s. r.
						LL r. s.	scar	w. r.
				re-thoracotomy l. s.	44 months (since l.s. re-thoracotomy)	UL I. S.	1 (2 cm)	s.r.
3	F	14 y	osteosarcoma	preoperative ChT					46 m	NED
			(distal femur l. s.)	primary tumor resection resection bone metastasis	24 months
				bilateral thoracotomy	25 months	UL r. s.	2	w.r.
						LL r. s.	6	w.r.
						UL l. s., LL l. s.	5 each	w.r.
4	F	12 y	osteosarcoma	preoperative ChT					14 m	NED
			(distal femur l. s.)	tumor resection
				bilateral thoracotomy	22 months	LL l. s., LL r. s.	2 each	w.r.
				re-thoracotomy l. s.	16 months (since thoracotomy)	UL I. S.	1 (3 cm)	s.r.
						LL I. S.	2	w.r.
5	M	3 y	hepatoblastoma IV	preoperative ChT					59 m	NED
				tumor resection
				thoracotomy r. s.	6 months	UL r. s., ML r. s.	1 each	w.r.
						LL r. s.	4	lobectomy
				thoracotomy l. s.	8 months	UL l. s.	5	w.r.
						LL I. S.	2	w. r.
				re-laparotomy	10 months	right liver lobe	scar
				re-thoracotomy r. s.	8 months (since r. s. thoracotomy)	UL r. s.	1 (5 cm)	s.r.
				re-thoracotomy l. s.	6 months (since l. s. thoracotomy)	UL I. s., LL I. S.	2 each	s./w.r.
6	M	2 y	hepatoblastoma IV	preoperative ChT					65 m	NED
				tumor resection
				bilateral thoracotomy	0 months	LL l. s., LL r. s.	4 each	w. r.
7	M	2 y	hepatoblastoma IV	preoperative ChT					66 m	NED
				tumor resection
				thoracotomy r. s.	7 months	LL r. s.	2 (5 cm)	s.r.

Table 1 continued

No.	Sex	Age (at diagnosis)	Primary malignancy	Therapy	Interval to pulmonary metastasis/ recurrence of primary tumor	Location of metastases	Nodules (number)	Type of excision	Follow- up	Outcome
8	F	13 y	MPNST (upper arm l.s.)	primary tumor resection					61 m	NED
				local re-resection	14 months
				local re-resection	12 months
				local re-resection	30 months			w.r.
				thoracotomy r. s.	56 months	ML r.s., UL r. s.	2 each	lobectomy
				re-thoracotomy r. s.	14 months (since r. s. thoracotomy)	ML r. s.,	5	w.r.
						LL r. s.	2	w.r.
9	F	16 y	AC	primary tumor resection						DoD
				thoracotomy r. s.	0 months	UL r. s.	3	w.r.
						ML r. s.	8	w.r.
						LL r. s.	10	w.r.
				re-thoracotomy r. s.	local bleeding			hemostasis
				thoracotomy l. s.	0 months	UL l. s.	6	w.r.
						LL I. S.	multiple	lobectomy
10	F	14 y	RMS	preoperative ChT					26 m	NED
				tumor resection
				thoracotomy l. s.	0 months	UL l. s.	3	s.r.
				resection metast. nodule	26 months	left mamma

r. s.: right side; l. s.: left side; dg.: diagnosis; UL: upper lobe; ML: middle lobe; LL: lower lobe; w. r.: wedge resection; s. r.: segment resection, m: months; NED: no evidence of disease; DoD: died of disease

cells. 61 months after the last thoracotomy, the girl showed no evidence of disease.

In patient no. 9, a good regression of multiple bilateral pulmo- nary metastases of AC due to multimodal ChT was the indication for bilateral thoracotomy. However, complete removal of all pal- pable metastases was not possible without risking severe respi- ratory insufficiency, and the girl died of recurrent metastatic dis- ease 2 months later.

A suspicious nodule in the right mamma was the first clinical sign in patient no. 10, a 14-year-old girl. Fine-needle biopsy was performed, and histopathologic evaluation showed metastatic RMS, with the primary malignancy at the right foot. Diagnostic staging revealed metastatic nodules in the upper lobe of the left lung. The primary malignancy as well as the metastases showed a good response to preoperative induction ChT following the CWS protocol. Therefore, amputation of the primary tumor and of the metastatic nodule of the mamma was performed as well as thoracotomy with segment resection of the upper lobe one week later. 26 months after the thoracotomy, a metastatic nod- ule in the left mamma was diagnosed. Staging carried out prior to complete resection revealed no evidence of other metastatic disease, in particular, no evidence of pulmonary nodules.

Discussion

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Thoracotomy is a safe and simple procedure with a low operative mortality in children. Therefore, it is widely used for the treat- ment of primary or metastatic malignant diseases confined to the thoracic cavity [2,15]. Several authors recommend pulmo- nary metastasectomy in cases with unilateral pulmonary dis- ease due to pediatric solid malignancy [1,2,5,9,12,17]. In chil- dren with bilateral and/or multiple pulmonary metastases as well as recurrent metastatic disease, the benefit of an aggressive surgical treatment is still discussed controversially [16]. Most of the primary malignancies in childhood have well established treatment protocols for medical therapy, and are associated with good survival rates [3,4,6,7,10,11,14,17]. Therefore, actual treat- ment protocols and treatment measures have to aim at reducing the morbidity associated with treatment without impairing the cure rates.

Since many of the pulmonary metastases are located peripher- ally in the lung, thoracoscopic removal (VATS) of these lesions has become feasible. However, this technique can identify only superficial, visible metastases. Centrally located nodules cannot be detected. Additionally, sometimes there is a discrepancy be- tween the number of radiologically visible metastases and the palpable nodules, and many more metastases are identified dur- ing surgery by manual palpation than by CT [16]. Our results confirmed this experience and corroborate the concept of using open surgery. Some authors recommend a median sternotomy for routine bilateral lung exploration [8]. In our and others [16] experience, a lateral thoracotomy allows a better access to basal and posteriorly located lung segments as well as to lymph nodes. In addition, we have to take account of the risk of intraoperative respiratory insufficiency after extensive unilateral lung resec- tion, which is the reason why we prefer a staged bilateral thora- cotomy.

The efficacy of excising pulmonary metastases depends on sev- eral factors. First, complete resection of the primary tumor offers the best chance for survival by eliminating the source of further metastatic spread. Second, the longer the interval between diag-

nosis or resection of the primary tumor and the development of chemotherapy-resistant metastases, the better the chance of survival [5,16]. Third, effective chemotherapy, evidenced by de- clining tumor marker levels and disappearing radiological find- ings, improves survival by eliminating microscopic disease and shrinking macroscopic lesions to enhance resectability. With re- gard to these facts, pulmonary metastasectomy may increase survival in carefully selected children.

Eight out of 10 children in our series confirm these selection cri- teria. Although we treated only 3 patients with HB, our results emphasize the necessity of an aggressive surgical treatment in carefully selected patients with HB. However, Uchiyama et al. re- ported a poor prognosis for patients with pulmonary metastases secondary to HB, despite adjuvant ChT [17], which is contradic- tory to our experience and emphasizes the importance of careful patient selection.

Retrospectively, the clinical course of patient no. 1 who died of metastatic disease also corroborates the above statements. The girl presented with pulmonary metastases at time of diagnosis, and showed no relevant response to preoperative ChT. Neverthe- less, even in the case of an excellent response to preoperative ChT, the outcome of some tumors may be poor, as seen in patient no. 9. The clinical course and intraoperative findings of this pa- tient illuminate another relevant problem. Sometimes there is a discrepancy between the number of radiologically visible me- tastases and the palpable nodules, and many more metastases are identified during surgery than by CT [16]. In our patient, the number and size of the intraoperatively palpable pulmonary metastases made complete removal of all pulmonary metastases impossible. Bilateral thoracotomy had no benefit for these 2 pa- tients.

Although our study included only 10 patients, we report on the benefit of 29 thoracic surgical procedures. Multiple unilateral and bilateral thoracotomies were successful in achieving the long-term survival of 7 children (patient no. 4 has had a follow- up of only 14 months) in this series. Bilateral thoracotomy car- ried out as a single procedure, combined with laparotomy in one patient, was well tolerated in 4 patients. In addition to a good operative technique, the success of the surgical procedure also depends on the correct indication. Summarizing study re- ports of others and our results, we conclude that bilateral and/ or recurrent unilateral thoracic surgery may represent a thera- peutic option for carefully selected patients. Indications must be based on strict criteria. These should include no evidence of residual or recurrent primary malignancy, no evidence of extra- pulmonary metastatic disease, effective preoperative ChT with regression and a subsequent decrease in the number and size of pulmonary metastases, and the assessment as surgically resect- able disease without the risk of postoperative residual pulmo- nary insufficiency. Regarding these criteria, patients suffering from pulmonary metastases due to primary malignancies such as OS and HB as well as MPNST and RMS may benefit from lung surgery. Neither bilateral nor recurrent metastases are a contra- indication for surgical intervention if the lesions are amenable to resection, whereas the presence of pulmonary metastases at the time of initial diagnosis represents an unfavorable factor.

Résumé

L’intérêt du traitement chirurgical devant des métastases pulmonaires bilatérales et/ou multiples chez l’enfant

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Buts: La chirurgie pulmonaire est fréquemment utilisée pour le traitement des métastases de l’enfant dans de multiples lésions malignes. Le bénéfice d’un traitement chirurgical agressif chez l’enfant pour des métastases bilatérales et/ou multiples est en- core discuté.

Méthodes: L’analyse rétrospective de 10 enfants (7 filles et 3 gar- çons) d’âge moyen de 2 à 16.5 ans qui ont subi une thoracotomie pour des lésions bilatérales et/ou multiples a été réalisée. La tu- meur maligne était un ostéosarcome N =4, un hépatoblastome N = 3, une tumeur nerveuse périphérique maligne N = 1, un carci- nome surrenalien N= 1 et un rhabdomyo-sarcome alvéolaire N = 1. Une métastase unique unilatérale mais multiple était re- trouvée chez trois enfants qui avaient des métastases pulmonai- res bilatérales. La chimiothérapie d’induction pré-opératoire avec régression de la tumeur et une diminution en taille et en nombre des métastases pulmonaires était obligatoire avant toute chirurgie.

Résultats: Une thoracotomie bilatérale était réalisée chez 4 pa- tients (en un temps chez un patient associé à une hépatectomie et chez 3 patients en deux opérations différées). 5 enfants ont subi une seconde thoracotomie pour récurrence des métastases pulmonaires (2 patients à métastases unilatérales, 3 patients à métastases bilatérales, 1 patient à métastases 2 fois bilatérales). Toutes les métastases visibles et palpables (1 à 25) étaient enle- vées soit par résection atypique, soit par résection segmentaire, soit par lobectomie. Les ventilations artificielles étaient néces- saires en post-opératoire de 0 à 24 heures. Les complications post-opératoires incluaient une hémorragie intra-thoracique se- condaire dans 3 cas et une pneumonie dans un cas. 2 patients (20%) mourraient de métastases récurrentes (ostéosarcome 1, carcinome surrénalien 1). Durant une période de suivi de 49 mois (14 à 66 mois après la dernière thoracotomie), 8 patients (80%) restaient en rémission complète sans manifestation respi- ratoire.

Conclusion: La résection chirurgicale des métastases pulmonai- res après réponse à une chimiothérapie d’induction augmente la survie chez les patients, même chez ceux qui présentent des métastases multiples ou récurrentes. Chez l’enfant, une thoraco- tomie bilatérale en un seul temps est possible sans augmenter le risque de complication.

Resumen

Utilidad del tratamiento quirúrgico de las metástasis bilaterales o múltiples en niños

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Objetivos: Se usa frecuentememnte cirugía pulmonar para el tra- tamiento de las metástasis en niños con varios tumores pero el beneficio de este tratamiento agresivo en niños con metástasis bilaterales o múltiples es motivo de controversia.

Métodos: Estudiamos retrospectivamente 10 niños (7 chicas y 3 chicos) de edades entre 2 y 16.5 años que sufrieron toracotomía por metástasis pulmonares bilaterales o múltiples. Los tumoresa primarios fueron osteosarcoma (n =4), Hepatoblastoma (n =2), tumor maligno de vaina nerviosa periférica (n=1), carcinoma

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adrenocortical (n=1) y rabdomiosarcoma alveolar (n=1). Tres niños tenían metástasis unilaterales pero múltiples mientras que 7 las tenían en ambos lados. Se indujo regresión tumoral con quimioterapia antes de la operación.

Resultados: Se practicó toracotomía bilateral standard en 4 pa- cientes en una sola operación (en 1 combinada con hemihepa- tectomía) y en 3 pacientes en dos operaciones en días diferentes. Cinco niños hubieron de ser reoperados por nuevas metástasis (2 en un lado, 3 en los dos y 1 dos veces en ambos lados). Todas las metástasis visibles y palpables (1-25) fueron extirpadas me- diante resección en cuña, extirpación de un segmento o lobecto- mía. Los pacientes fueron ventilados durante 24 horas en el post- operatorio. Las complicaciones incluyeron hemorragia intratorá- cica (n=3), y neumonía (n = 1). Dos pacientes (20%) murieron de enfermedad metastásica recidivante (1 osteosarcoma y 1 carci- noma suporarrenal). Los niños han sido seguidos una media de 49 meses (rango 14 a 66 m) y 8 (80%) permanecen libres de en- fermedad sin limitaciones respiratorias.

Conclusión: La resección quirúrgica completa de las metástasis tras quimioterapia de inducción puede incrementar la supervi- vencia en niños seleccionados incluso cuando las metástasis son múltiples o bilaterales. En niños la toracocomía bilateral en una sola operación es posible sin aumentar la tasa de complica- ciones.

Zusammenfassung

Die Relevanz chirurgischer Maßnahmen bei bilate- ralen und/oder multiplen Lungenmetastasen im Kindesalter

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Hintergrund: Die Lungenchirurgie hat bei der Behandlung solitä- rer Metastasen verschiedener Malignome im Kindesalter eine wesentliche Bedeutung. Der Nutzen eines aggressiven chirurgi- schen Vorgehens bei Kindern mit bilateralen und/oder multi- plen unilateralen Lungenmetastasen wird auch heute noch kon- trovers diskutiert.

Methoden: Wir analysierten retrospektiv die Daten von 10 Kin- dern (7 Mädchen und 3 Jungen im Alter von 2 bis 16,5 Jahren), bei denen aufgrund bilateraler und/oder multipler unilateraler Lungenmetastasen eine Thorakotomie durchgeführt werden musste. Primärerkrankungen waren Osteosarkom (n = 4), Hepa- toblastom (n=3), maligner peripherer Nervenscheidentumor (n=1), Nebennierenkarzinom (n=1) und alveoläres Rhabdo- myosarkom (n = 1). Unilaterale aber multiple Lungenmetastasen wurden bei 3 Kindern gefunden. 7 Kinder zeigten bilaterale Lun- genmetastasen. Eine präoperative Chemotherapie mit Tumorre- gression und nachfolgender Reduktion von Grösse und Anzahl der Lungenmetastasen waren Voraussetzung für die Indikation zum chirurgischen Vorgehen.

Ergebnisse: Bei 4 Kindern erfolgte eine bilaterale Thorakotomie innerhalb derselben Narkose (bei einem Patient kombiniert mit einer Hemihepatektomie), bei 3 Kindern im Rahmen von 2 Ope- rationen an jeweils aufeinander folgenden Tagen. Bei 5 Patienten musste eine Re-Thorakotomie aufgrund eines Lungenmetasta- sen-Rezidives durchgeführt werden (2 Kinder: unilateral; 3 Kin- der: bilateral; 1 Kind: zweimal bilateral). Alle sichtbaren und palpierbaren Metastasen (1-25) wurden exzidiert, entweder mittels Keilresektion, Segmentresektion oder Lobektomie. Post-

operativ mussten die Kinder für 0-24 Stunden nachbeatmet werden. Postoperative Komplikationen waren intrathorakale se- kundäre Blutung (n=3) und Pneumonie (n= 1). 2 Kinder (20%) verstarben aufgrund eines Metastasen-Rezidives (Osteosarkom bzw. Nebennierenkarzinom). Während eines mittleren Nach- beobachtungszeitraumes von 49 Monaten (14 bis 66 Monate nach dem letzten Eingriff) blieben 8 Kinder (80%) in Voll-Remis- sion, ohne klinisch relevante pulmonale Einschränkung.

Zusammenfassung: Die komplette chirurgische Entfernung von Lungenmetastasen nach erfolgreichem Ansprechen auf die prä- operative Chemotherapie kann die Überlebensrate sorgfältig ausgewählter Patienten deutlich verbessern, dies sogar bei Vor- liegen multipler und rezidivierender Lungenmetastasen. Im Kin- desalter kann eine bilaterale Thorakotomie innerhalb einer Nar- kose durchgeführt werden, ohne eine erhöhte Komplikations- rate riskieren zu müssen.

References

1 Abel RM, Brown J, Moreland B, Parikh D. Pulmonary metastasectomy for pediatric solid tumors. Pediatr Surg Int 2004; 20: 630-632

2 Baldeyrou P, Lemoine G, Zucker JM, Schweisguth O. Pulmonary metasta- ses in children: the place of surgery. A study of 134 patients. J Pediatr Surg 1984; 19: 121 - 125

3 Bielack SS, Kempf-Bielack B, Delling G et al. Prognostic factors in high- grade osteosarcoma of the extremities or trunk: an analysis of 1702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2002; 20: 776-790

4 Bielack SS, Jürgens H. Surgical expertise and outcome in osteosarcoma trials. J Clin Oncol 2004; 22: 2511 - 2513

5 Black CT, Luck SR, Musemeche CA, Andrassy RJ. Aggressive excision of pulmonary metastases is warranted in the management of childhood hepatic tumors. J Pediatr Surg 1991; 26: 1082 - 1086

6 Brecht IB, Treuner J. Soft tissue sarcoma in children and adolescents: experience of the cooperative Soft Tissue Sarcoma Group Studies (CWS-81-96). Handchir Mikrochir Plast Chir 2004; 36: 275 - 281

7 Fuchs J, Rydzynski J, von Schweinitz D et al. Pretreatment prognostic fac- tors and treatment results of hepatoblastoma in childhood - a report from the German Cooperative Pediatric Liver Tumor Study HB94. Can- cer 2002; 95: 172 - 182

8 Goncalves de Oliveira-Filho A, Sbragia Neto L, Epelman S. Median ster- notomy for the resection of bilateral pulmonary metastases in chil- dren. Pediatr Surg Int 1998; 13: 560-563

9 Green DM, Breslow NE, Yoichi I et al. The role of surgical excision in the management of relapsed Wilms’ tumor patients with pulmonary metastases: a report from the National Wilms’ Tumor Study. J Pediatr Surg 1991; 26: 728 -733

10 Haeberle B, Bode U, von Schweinitz D. Differentiated treatment protocols for high- and standard-risk hepatoblastoma - an interim report of the German Liver Tumor Study HB99. Klin Paediatr 2003; 215: 159 - 165

11 Kager L, Zoubek A, Potschger U et al. Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooper- ative Osteosarcoma Study Group protocols. J Clin Oncol 2003; 21: 2011 -2018

12 Karnak I, Senocak ME, Kutluk Tet al. Pulmonary metastases in children: an analysis of surgical spectrum. Eur J Pediatr Surg 2002; 12: 151 - 158

13 Koscielniak E, Morgan M, Treuner J. Soft tissue sarcoma in children: prognosis and management. Paediatr Drugs 2002; 4: 21 - 28

14 Parlowsky T, Dralle H, Farahati J et al. Malignant endocrine tumours in children. Dt Aerztebl 2001; 98: A764-A767

15 Rusch VW. Pulmonary metastasectomy. Current indications. Chest 1995; 107: 322S-331S

16 Su WT, Chewning J, Abramson S et al. Surgical management and out- come of osteosarcoma patients with unilateral pulmonary metastases. J Pediatr Surg 2004; 39: 418- 423

17 Uchiyama M, Iwafuchi M, Naito M et al. A study of therapy for pediatric hepatoblastoma: prevention and treatment of pulmonary metastasis. Eur J Pediatr Surg 1999; 9: 142- 145

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