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Application of interventional bronchoscopic therapy in eight pediatric patients with malignant airway tumors
Hongwu Wang, Nan Zhang, Meimei Tao, Dongmei Li, Yunzhi Zhou,
Hang Zou, Sujuan Liang, and Jing Li
Minimal Invasive Tumor Therapy Center, Beijing Coal General Hospital, Beijing, China
airway, bronchoscopy, children, malignant tumor.
Hongwu Wang, Minimal Invasive Tumor Therapy Center, Beijing Coal General Hospital, No 29 Xibahe Nanli, Chaoyang Distric, Beijing 100028, China.
Received September 2, 2011;
accepted May 16, 2012.
Aims and background.
Malignant airway tumors in children have rarely been reported. We evaluated the safety and therapeutic effects of interventional bronchoscopic therapy in 8 children with malignant airway tumors.
Methods and study design.
We retrospectively analyzed 8 children with malignant airway tumors diagnosed by pathology, and evaluated their clinical features, chest computer tomography findings and bronchoscopic manifestations.
Two of the 8 pediatric patients had high-grade malignancies (lymphoma and sarcoma) and the others all had low-grade malignancies, including 2 cases with mucoepidermoid carcinoma and 4 cases with inflammatory myofibroblastic tumor. Their ages ranged from 4 to 8 years (mean, 5.7 ± 0.9). There were no specific clinical manifestations in the children, and all of them presented with various respiratory symptoms, including cough and gasping associated with hemoptysis. Chest CT indicated round intra-airway neoplasms. Obstructive pulmonary atelectasis occurred in the main bronchus of 4 patients (3 cases of the left main bronchus and 1 case of the right intermedius bronchus). All children (1 case with local anesthesia and 7 cases with general anesthesia) underwent interventional bronchoscopic therapy, including argon plasma coagulation and CO
cryosurgery. The success rate for the rigid procedures was 100.0% (7/7), and the cure rate after 3 months was 85.7% (6/7). A part of the tumor remained in the lung of 1 patient with inflammatory myofibroblastic tumor after bronchoscopic treatment. One patient with local anesthesia died of suffocation caused by tumor consolidation during the bronchoscopic procedure. There were no recurrences in 6 patients during the follow-up period. One recurred patient was cured at 6 months.
There are no specific manifestations in children with malignant airway tumors. Interventional bronchoscopic therapy seems to be safe and effective for those tumors under general anesthesia.
The pediatric trachea and bronchus are notable for the following features: the lumens are narrow; the tracheal cartilages are weak; there are rich tunica mucosa tracheal vessels; the development of the elastic tissue in lumens is poor; and ciliary function is relatively weak. Congenital diseases and inflammation are more common than tumors in pediatric airways, and primary tracheal malignant neoplasms are extremely rare lesions and are often misdiagnosed
. With the progression of interventional bronchoscopic technology in pediatrics, its indications have increased, not only in the diagnosis of airway diseases, but also in its therapeutics. Interventional bronchoscopy is a modality increasingly accepted by pediatricians, otorhinolaryngologists and surgeons and has been widely used in the treatment of airway tumors in adults. Argon plasma coagulation (APC), CO
cryosurgery, laser, endoprosthesis and photodynamic therapies are often adopted in the therapy
. However, the application of these techniques is rare in pediatric patients. Currently, there is no bronchoscopic instrument specially designed for the treatment of children. The application of a rigid bronchoscope in children is used mainly to remove foreign bodies
In recent years, we have treated 8 pediatric patients with unresectable malignant airway tumors using interventional bronchoscopic therapies.
Patients and methods
We retrospectively analyzed 8 pediatric patients, 6 males and 2 females, admitted to our hospital between December 2006 and June 2010. Their ages ranged from 4 to 8 years (mean, 5.7 ± 0.9). Two patients had high-grade malignant tumors (lymphoma and sarcoma) and the other patients all had low-grade malignant tumors (2 cases of mucoepidermoid carcinoma and 4 cases of inflammatory myofibroblastic tumor).
One child underwent electronic flexible bronchoscopy with local anesthesia, and 7 patients underwent rigid bronchoscopy with general anesthesia. Various examinations were performed preoperatively, including routine blood tests, electrocardiogram, blood oxygen saturation, blood gas analysis, pulmonary function tests, chest X-rays and CT scans. The preoperative assessments and anesthesia assessments were performed by anesthesiologists and pulmonologists. The movements of the mouth, teeth, jaw bones and neck were carefully examined. Informed consent was obtained from the parents of each study patient.
Local anesthesia: One percent amethacaine was sprayed in each patient for local anesthesia, and 0.1% lidocaine was then sprayed in locally after entering with the bronchoscope without intravenous anesthesia.
Oxygen was given by a face mask on the patient for general anesthesia to achieve preoxygenation for 5 to 10 min before anesthesia. Either 0.5 mg atropine or 0.3 mg hyoscine was administered by intravenous drip 10 min preoperatively to inhibit excessive secretions in the airway. Blood oxygen saturation, electrocardiogram, blood pressure readings and respiratory movements were monitored intraoperatively.
Midazolam, 2 mg (anti-anxiety and anti-amnesic drug), was intravenously administered 5 min before the anesthesia to prevent the children from acquiring frightening memories of the surgical experience, which can then be recalled after the procedure. Subsequently, fentanyl (1-2
g/kg) and 1% propofol (1-2 mg/kg body weight) were intravenously administered until disappearance of the patient’s lash reflex and response reactions. Skelaxin atracurium, at a dose of 0.5 mg/kg, was then administered, and the rigid bronchoscope was inserted until the disappearance of muscle trembling and the initiation of muscle relaxation in the lower mandible. The patients’ eyes and teeth were protected during general anesthesia.
Insertion methods of the rigid bronchoscope.
The rigid bronchoscope
diameter) of Karl Storz (Karl Storz GmbH & Co
Tulingen, Germany) was used in the procedures. The patients lay in a supine position on the bed. A cushion was placed under the patient’s shoulders to keep the head leaning back, convenient for the insertion of the rigid bronchoscope. The procedures of rigid bronchoscopy can be performed with the guide of an indirect laryngoscope or direct vision, and a high-frequency jet ventilator can be connected after insertion into the trachea.
For glottic or subglottic tumors, the front end of the rigid bronchoscope needs only to cross the glottis, and this can be performed by the assistant.
Maintenance of anesthesia.
A concentration of 1% propofol, 1-2 mg/kg•h
, and remifentanil, 0.1-0.2
, are used for the anesthesia. The general anesthesia required for insertion of the rigid bronchoscope is less than that needed for surgery. It is proper to inhibit spontaneous breathing slightly but not totally. The anesthetics were discontinued at the end of the procedure. When the patient’s blood oxygen saturation reached over 95% and lasted for 5 min, and if the patient did not inhale oxygen in the resting state before waking, he/she could return to the ward.
The anesthetic machine and high-frequency ventilation.
Mechanical ventilation can be connected through the lateral pore of the rigid bronchoscope. The common types of ventilation are assisted mechanical ventilation, controlled mechanical ventilation and manual balloon compression with spontaneous breathing. Generally, the anesthetic machine was first connected to the patient at the beginning of anesthesia to maintain the oxygen saturation at 100%. High frequency jet ventilation was then used at a frequency of 40-80 times/min, and a three-way pipe was connected to the respiratory tube before performing the interventional therapy. The various examinations and therapies were carried out without pausing the respiratory machine. If the high-frequency jet ventilation cannot maintain enough oxygen saturation long enough for bronchoscopy, the anesthetic machine can be exchanged. In addition, manual balloon compression can be used if necessary, and the blood oxygen saturation should be maintained at over 100% for the continuous procedure.
Interventional bronchoscopic modalities.
The various interventional modalities were performed through the hole at the posterior extremity of the rigid bronchoscope. Both APC and CO
cryosurgery can be applied under the guidance of the rigid instrument for the treatment of tumors in the main trachea, whereas they must be guided by the electronic flexible bronchoscope PENTAX-EPM 3500 (Pentax Ricoh Imaging Co, Ltd Tokyo, Japan) for tumors in the bronchus.
The applied instrument was a Cesel type 3000 (Soring GmBH, Germany). The APC probe was stretched out of the insertion through the biopsy channel of the electronic bronchoscope (the probe marker that can be seen was set as the standard) and began to cauterize at a distance of from the foci. The output power of the APC probe was 30-50 W, and the flow rate of argon was 0.8/min. There was no need to stop the inhalation of oxygen during the cauterization. Interrupted cauterization should be used, but not for too long. The coagulated tissue should be taken out using biopsy forceps or cryoprobes.
A freezing therapeutic instrument (ERBE Co., Tubingen, Germany) was applied in the study. The diameter of the flexible cryoprobe was 1.5 mm, and the terminal length of the probe was 5 mm. The cryogen was liquid carbon dioxide. The metal head of the freezing probe was placed on the surface of the tumor or was pushed into the tumor to freeze it for 5-10 s in order to generate an ice ball surrounding the probe. Subsequently, the probe and its cryoextracted tissue were removed in a frozen state. The probe was inserted again until all the tumors in the lumen were removed. If hemorrhage occurred after cryoextraction, APC was used to stop the bleeding.
Four cases of pediatric patients with inflammatory myofibroblastoma (IMT)
The ages of the 4 children were 5, 5, 8 and 9 years, respectively, including 3 males and 1 female. Two of the children were initially misdiagnosed as pneumonia and bronchial tuberculosis. The other 2 cases were diagnosed as left pulmonary atelectasis. All of the tumors originated from the left main bronchus: two were located in the orifices of the left main bronchus and involved the lower extremity of the main bronchus, and the others were located in the middle and inferior part of left main bronchus. All of the clinical manifestations of the patients were reflected as respiratory infections such as cough and fever, and none improved after antibiotic treatment. CT scan showed that there were round or orbicular-ovate neoplasms in the airway. Two cases were diagnosed as pulmonary atelectasis. The polyp neoplasms with abundant blood vessels can be seen under bronchoscope (Figures 1 and 2), and the tumors were scavenged by CO
cryosurgery combined with APC. All of them were pathologically diagnosed as IMT (Figure 3). The follow-up time was 2-10 months. One case showed recurrence after follow-up at 2 months and cure at 6 months, and the others had no disease progression after a follow-up at 10 months.
Two cases of mucus epidermoid carcinoma (MEC).
Two children, both males aged 4 and 7 years, were admitted to our hospital for cough, hemoptysis and fever of more than 3 years duration and recurrent cough accompanied by fever for 1 year. One of them with MEC, aged only 7 months at the onset of symptoms, did not undergo bronchoscopy until 4 years of age, despite suffering from frequent obstructive pneumonia. Both of them had pulmonary atelectasis when they were admitted to our unit. In one child, chest X-ray and CT examinations indicated a solid lesion in the dorsal and posterior segment of the left lower lobe accompanied by left lower pulmonary atelectasis. In the other child, pulmonary CT scan indicated a high-density occupation in the right intermedius bronchus accompanied by atelectasis in the middle lobe of the right lung and inflammation in the inferior lobe of the right lung. The two cases had undergone rigid bronchoscopy under general anesthesia, and the inferior extremity of the left main bronchus was partially obstructed by the neoplasm in one patient (Figure 4); the right intermedius bronchus was completely obstructed in the other (Figure 5). All of the tumors were removed by cryoextraction and APC. The pathological results were reported as MEC. Pulmonary atelectasis (in 2 cases) resolved immediately after bronchoscopic treatment. The children were so young that their parents could not agree to perform pneumonectomy or lobectomy, even though the surgeons suggested that left pneumonectomy or right middle inferior lobectomy should be performed. After two years and one year of follow-up respectively, neither of them has had a recurrence.
One case of a pediatric patient with tracheal malignant lymphoma
The 8-year-old child, a female, came to the outpatient clinic of our hospital for treatment on December 27
, 2006, for cough and suppression of breathing of more than 1 year duration. The patient had had similar symptoms without an evident cause in October 2005, and she was thought to be suffering from bronchial asthma. She therefore received spasmolysis and asthma therapy, but the therapeutic effects were not favorable. A chest CT examination indicated a neoplasm in the middle of the trachea and she subsequently underwent tumor resection. The pathological diagnosis was malignant lymphoma, and
the tumor was completely removed. The patient did not receive general chemotherapy after the surgery because of rejection by her parents. After half a year, the breathing suppression returned, and bronchoscopy indicated that the neoplasm had reappeared in the trachea and occupied the lumens. She was transferred to our emergency room for treatment. The physical examination at that time showed the following: Karnofsky performance score at 60%, a short breathing index at grade III (stopped walking due to shortness of breath when walking normally), and a heart rate of 140 beats/min (she also suffered from congenital heart disease). High-pitched stridor could be heard in the front of the heart. Bronchoscopy was performed under local anesthesia, and multiple polypoid neoplasms were found in the upper middle position of the trachea, which showed a flap-type movement during respiration. More than 90% of the lumen was obstructed by the tumor (Figure 6A). APC was then performed in order to ablate the tumor. After 10 min, the lumen was abruptly occluded by the stiff and outpunching neoplasmas, which were deformed by the APC (Figure 6B). The patient died immediately from suffocation. After an urgent nasal trachea cannula was applied and respiration was assisted by a respirator, her heart rate remained zero; she was declared deceased one hour later.
One case of a pediatric patient with tracheal fusocellular sarcoma
The 6-year-old female child came from another hospital. She was initially admitted to the Tianjin Childrens’ Hospital of China in September 2008 and had a recurrence in May 2009; unfortunately, there was no further treatment. The patient was not suitable for tracheotomy upon consultation at many famous hospitals in Beijing and Tianjing. The chest CT scan in October 2009 indicated that the neoplasm in the trachea had increased (Figure 7A), and nodules and a strip shadow had appeared under the pleura of the middle lobe of the right lung.
She was admitted to our hospital on November 5
, 2009, for labored breathing accompanied by cough and hemoptysis of more than 1 year duration. The patient appeared to evidence breathing suppression accompanied by cough and a small quantity of hemoptysis without an evident cause, and she was thought to be suffering from pneumonia and bronchiectasis. However, antibiotic therapy had no benefit, and the chest CT scan indicated a neoplasm in the middle portion of the trachea. A soybean-sized swelling was taken out by bronchoscopy and was diagnosed histologically as a intermediate-grade differentiated fusocellular sarcoma. Radio- and chemotherapy were subsequently administered.
Physical examination upon admission showed the following: Karnofsky performance score was 90%, and the short breathing index was grade III. Stridor could be heard in the front of her heart. Bronchoscopy was performed in the operating room under general anesthesia, and the globular neoplasm was found in the lower end of the trachea (Figure 7B). In this location, the mucosal surface is smooth and glossy with abundant and crisp blood vessels, all of which hemorrhage easily. Over 50% of the lumen was obstructed by a soybean-sized neoplasm which involved of the length of the trachea. The neoplasm was removed by APC and cryoextraction. After the treatment, the neoplasm disappeared, and the lumen reopened. There has been no recurrence at one year of follow-up.
Malignant neoplastic diseases of the pediatric airway are evidently different from those in adults, in whom squamous cell carcinoma and adenocarcinoma occur primarily
. However, these malignant tumors rarely occur in children, even though IMT and MEC are common
. In this study, only 2 of 8 pediatric patients had high-grade malignancies (lymphoma and sarcoma), and the others all suffered from low-grade malignancies (MEC and IMT). One patient was only 7 months old at the onset of symptoms; the oldest was 8 years old, and the mean age was 5.7 ± 0.9 years.
There are no specific clinical manifestations in children with malignant tumors. It has been reported that cough, pneumonitis, fever, respiratory distress, hemoptysis, chest pain and wheezing are the most common signs and symptoms
. All 8 pediatric patients had chronic cough. Four patients with main trachea tumors were misdiagnosed with bronchitis or bronchial asthma, and the others (3 located in the left bronchus and 1 located in the right intermedius bronchus) had obstructive atelectasis, including one patient misdiagnosed with bronchial tuberculosis. However, no evident therapeutic effects were achieved after antibiotic treatment in all of the patients.
IMT is a rare tumor that mainly occurs in pulmonary tissue; tumors that occur primarily in the trachea (about 10%) have rarely been reported
. The final diagnosis depends on the pathological results. Histology in pulmonary IMT shows differentiated myofibroblast spindle cells, accompanied by numerous plasma cells and/or lymphocytes. The clear boundary of the tumor, the augmented nodule shadow, and the multiple polypoid neoplasms could be detected by CT scan.
MEC occurs mainly in school-age children but has also been reported, albeit rarely, in preschool children
. MEC originates from the gland under the mucosa of the bronchus tubal wall and belongs to the group of salivary gland carcinomas. There were no specific manifestations on CT examination. The roundish neoplasms in the lumens could be detected in the trachea, whereas the obstructive atelectasis could be seen in the bronchus. The polypoid neoplasms were discovered with sufficient blood vessels under the bronchoscope, and the hemorrhage appeared after palpation. The MEC swelling might be located in the trachea and bronchus, mainly in the segmental bronchus. In the present study, all four cases with IMT originated from the left main bronchus, and the neoplasms could easily be found in the airway. Two cases demonstrated whole left pulmonary atelectasis.
Peripheral T-cell lymphoma was previously diagnosed as malignant granuloma, idiopathic granuloma, and lethal midline granuloma. Peripheral T-cell lymphoma commonly occurs in the external part of a lymph node, including the nasal cavity, skin, digestive tract, respiratory tract, central nervous system, glands, and testis
. One case in this group had a lymphoma invading the tracheal wall with soft tissue neoplasms occupying the lumen, thereby inducing stenosis of the lumen. She was misdiagnosed with bronchial asthma and experienced a recurrence six months after initial surgical resection. Similar cases in adults have been reported worldwide, but no cases in children have yet been reported. It is important that the patient undergoes chemotherapy after surgery. It is an obvious consequence that the neoplasm reappeared half a year later.
Fusocellular sarcoma can occur in the striated muscle and the prostate, whereas the disease in a child’s trachea has not been previously reported. There were no specific clinical manifestations of this particular tumor, and the final diagnosis depends primarily on the pathology.
Surgery is considered to be the most effective treatment for malignant tumors of the airway, and patients can survive with tumors for several years even if they have undergone palliative resection. Massive bleeding can occur during the removal of the neoplasm, and a favorable therapeutic effect can be achieved by APC and a local injection of a coagulant drug. Therefore, interventional bronchoscopic therapy can be performed successfully under a laryngeal mask, a tracheal cannula or a rigid bronchoscope under general anesthesia. In our earlier experience, one child with lymphoma died under local anesthesia. The tumors had grown along the trachea wall and moved as a flap. The patient died of a sudden obstruction of the airway due to the consolidation of the tumors by APC, leading to suffocation. Therefore, general anesthesia is strongly recommended for the brochoscopic treatment of patients with severe tracheal stenosis. Tracheal cannula or cryoextraction combined with APC should be given at the beginning so as to avoid tract occlusion. Successful procedures were performed in the other 7 patients under rigid bronchoscope using general anesthesia. The cure rate was 85.7% (6/7) 3 months later. All of the patients who have undergone tumor bronchoscope surgery have had recurrent tumors, but in 3 cases (1 case with MEC and 2 cases with IMT) the tumors were resected and cryoablated, and no recurrence was found after a follow-up of 6 months to 1 year. The main consideration was that the children were too young to receive pneumonectomy. Interventional bronchoscopic treatment could control the disease and might not affect the child’s growth and development. With the growth of the children and improvement in their conditions, it is possible to have the best opportunity for pneumonectomy in the future.
Owing to the rarity of malignant airway tumors in children and adolescents, diagnosis is frequently delayed. When a child presents with recurrent pneumonia, respiratory distress, persistent cough, wheezing or hemoptysis, a malignant airway tumor should be considered. Interventional bronchoscopic therapy seems to be safe and effective for those tumors under general anesthesia based on the results of the present study. The children will be followed to evaluate the long-term effects.
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