Clinical Meetings at RH Year 2006

2006 KH: AN Uncommon Cause of Airway Obstruction

Dr SF Chui and Dr YN POON, Respiratory Medical Department, Kowloon Hospital

Case History
The patient was a 66 year old housewife, non-smoker, with history of carcinoma of left breast with left radical mastectomy done in 1996. She presented in June 2005 with one-month history of cough and whitish sputum. Physical examination and chest X ray were normal. Sputum cytology revealed cells suspicious of adenocarcinoma twice. Sputum for AFB by direct smear method was negative. The FEV1was 1.6L which was 88% predicted of normal value. The FEV1/FVC ratio was 73%. Fiberoptic bronchoscopy was done and showed mild mucosal swelling over bronchus of apical segment of left lower lobe. Bronchial aspirate for cytology and AFB by direct smear method were both negative. Bronchial biopsy of the mucosal swelling showed no evidence of malignancy. CT thorax also showed no lung opacity.



The patient was referred to Queen Mary Hospital and autofluorescence video-bronchoscopy was done in August 2005. Abnormal mucosal lesions were found at right main bronchus lateral wall just distal to level of carina, left main bronchus at the level of bifurcation to left upper lobe and left lower lobe and left upper lobe bronchus. Bronchoalveolar lavage fluid showed atypical cells. Multiple biopsies of the abnormal sites showed no malignancy.

The patient was then referred to Clinical Oncology Unit of Queen Elizabeth Hospital at September 2005. The diagnosis was probable early lung cancer with mucosal lesion, without gross tumour. Since the lesions were not operable due to involvement of bilateral main airways, intraluminal brachytherapy was offered. The patient admitted again for increased shortness of breath three months after brachytherapy. Chest X ray was normal. Spirometry showed obstructive pattern with FEV1 decreased by 50%. Flexible bronchoscopy was done and found lower trachea and carina swollen and covered with whitish materials. The left main bronchus and right lower lobe bronchus were narrowed by mucosal swelling and covered with whitish materials. Bronchial aspirate for cancer cell and AFB by direct smear method were again both negative. Bronchial biopsy of left main bronchus showed fibrinoid material with scanty atypical cells only. The diagnosis of irradiation bronchitis was made after discussion with the oncologist in the Queen Elizabeth Hospital. Despite intravenous hydrocortisone 100mg Q6h, patient deteriorated with SaO2 90% on 100% oxygen via non-rebreathing mask. CXR showed partial collapse of the right upper and lower lobes. Rigid bronchoscopy was done and found stenosis of both left and right bronchi. Both main bronchi were dilated. Stenting was done for the left main bronchus as well.




Discussion
Endobronchial brachytherapy
Brachytherapy is for palliation of inoperable carcinoma of the lung with endobronchial symptoms. The term "brachytherapy" is derived from the Greek word brachy, meaning short, and refers to the short distance, under 1 cm, between the radioactive source and the tumor volume to be irradiated. The radiation is therefore deposited where it is most required and is restricted to a short distance due to rapid falloff.1, 2 This permits effective treatment of endobronchial disease while at the same time bypassing the obstacle imposed by the radiation tolerance of surrounding normal tissue. The development of a high-dose-rate remote afterloading system has led to a breakthrough in this technique.3 It eliminates the radiation exposure hazard associated with the handling of radioactive sources. It does this by loading, or inserting, the radioactive material into catheters at a separate or remote location. Therefore, a highly radioactive source can be utilized. This permits a higher dose of irradiation to be delivered to the tumor volume in a shorter period of time. The brevity of the treatment (about 20 mins) is vital, since patient tolerance of an endobronchial catheter can be a limiting factor. Patients can now be treated on an outpatient basis at a tremendous cost savings.

Radiation bronchitis and stenosis may occur days or weeks after therapy and can manifest with cough or wheezing. Risk factors include large cell carcinoma histology, use of brachytherapy for curative intent, prior laser resection, and concurrent external beam radiation.5 Massive hemoptysis and bronchial necrosis or fistula formation are other serious late complications. It happens in 0 to 42 % of patient according to different reports.6,7

Radiation bronchitis and stenosis
Radiation bronchitis and stenosis was defined as a spectrum of clinical changes which occurred in the tracheobronchial tree following radiation.8 It usually develops 4 to 8 weeks after the last brachytherapy treatment. The incidence of radiation bronchitis ranges from 0% to 4%.8,9 Radiation bronchitis and stenosis is graded from grade 1 to grade 4.10 Grade I changes consisted of a mild mucosal inflammatory response with swelling, and characterized by a thin, whitish, circumferential membrane. The membrane did not have to be complete and occurred within the area of prior intraluminal radiation. There was no significant luminal obstruction caused by the membrane as evidenced by obstructive problems or by cough. Grade 2 changes consisted of an increase in the white fibrinous membrane with greater exudation causing symptoms such as cough and/or obstructive problems. Grade 3 was characterized by a severe inflammatory response with a marked membranous exudate. The associated fibrotic reaction was mild. The final progression was to a grade 4 level which was differentiated by the greater degree of fibrosis with resulting circumferential stenosis leading to a decrease in luminal diameter.

In the earlier grade lesions, histopathological changes consisted of a mild mucosal inflammatory response with swelling that contained an amorphous fibrinous and eosinophilic debris with varying amounts of entrapped white cells. Necrotic tumor cells and granulation tissues were also identified .The later grade responses were characterized by an increase in inflammatory changes with chronic inflammation and increasing fibrosis. A grade 4 reaction was characterized by a predominant fibrotic reaction seen in the deeper portions of the biopsy.

The treatment is observation for grade 1 reactions. For grade 2 reactions treatment is divided up into medical and procedurally related treatments. Medical treatment has consisted of steroid for 2 to 3 weeks and narcotic cough suppressants. Procedurally related treatment would consist of a single debridement. Grade 3 and 4 reactions required more aggressive therapeutic intervention. A grade 3 reaction was treated by multiple debridements via the bronchoscope. The most difficult reaction to control was the grade 4 reaction. Intervention required debridement, balloon or bouge dilatation, and stent placement. While the stents can be removed, it is not mandatory to do so since the stents can remain in place for long periods of time.

Reference:

1. Hilaris BS, Mastoras DA. Contemporary brachytherapy approaches in non-small-cell lung cancer. J Surg Oncol 1998; 69:258.
2. Raben A, Mychalczak B. Brachytherapy for non-small cell lung cancer and selected neoplasms of the chest. Chest 1997; 112:276S.
3. Seagren SL, Harrell JH, Horn RA. High dose rate intraluminal irradiation in recurrent endobronchial carcinoma. Chest 1985; 88:810.
4. Nag S, Kelly JF, Horton, JL et al. Brachytherapy for carcinoma of the lung. Oncology (Huntingt) 2001; 15:371.
5. Speiser B. Spratling I. Remote afterloading brachytherapy for the local control of endobronchial carcinoma. Int J Radiat Oncol Biol Phys 1993; 25:579.
6. Schray MF, McDougall JC, Martinez A et al. Management of malignant airway compromise with laser and low dose rate brachytherapy. The Mayo Clinic experience. Chest 1988; 93:264.
7. Seagren SL, Harrell JH, Horn RA. High dose rate intraluminal irradiation in recurrent endobronchial carcinoma. Chest 1985; 88:810.
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9. Cotter GW, Craig L, Ellingwood KE, et al: Inoperable endobronchial obstructing lung cancer treated with combined endobronchial and external-beam irradiation: A dosimetric analysis. Int J Radiat Oncol Biol Phys 27:531-535, 1993.
10. Speiser B, Spratling L. Intermediate-dose-rate remote afterloading brachytherapy for intraluminal control of bronchogenic carcinoma. Int J Radiat Oncol Biol Phys 18:1443-1448, 1990.