Therapeutic Approach to Surgically Resectable Typical Bronchial Carcinoid

The strategy of applying intraluminal bronchoscopic treatment (IBT) for patients with intraluminal typical bronchial carcinoid (ITBC) may well sound controversial. However, the relatively benign nature of typical carcinoid, its tendency for polypoid growth, and the low rate of metastatic disease (lymph nodes and distant), together with the advancements of bronchoscopic techniques for a more accurate diagnosis and staging and current abilities to treat intraluminal tumor bronchoscopically with curative intent, can offer alternatives to standard surgery. Recently, new bronchoscopic techniques have been developed and clinically applied to treat tumor in the central airways. 1 The feasibility of various BT modalities enables us to remove tumor located in the tracheobronchial tree in a safe and efficient way. For both malignant and benign conditions, the role of BT will certainly become increasingly important as our diagnostic and therapeutic abilities improve. 2 The role of BT in palliative care has been established to offer better quality of life for patients with central airway obstruction. Techniques are relatively straightforward in reopening the airway lumen for immediate symptomatic relief, either by removal of intraluminal tumor mass or by stent insertion for extraluminal compression. 3 Reports have described the role of bronchoscopic tumor removal in combination with surgical resection to enable a less extensive surgical resection. 4 This strategy is meant to spare as much normal lung tissue as possible. Frequently, tumor in the central airways may be located such that a radical surgery may result in a relatively wasteful resection of normal lung parenchyma. Clinical data have also shown that IBT may offer cure for patients with occult lung cancer. 5,6 Considerations for our new strategy of applying IBT first, versus the standard surgical resection, for selected patients with ITBC will be extensively discussed. TYPICAL VERSUS ATYPICAL HISTOLOGY Bronchial carcinoid accounts for less than 5% of all primary lung tumors and has been classified in the neuroendocrine group of tumors. 7 Well-differentiated carcinoid tumors constitute almost 90% of all bronchial carcinoids and they are mostly located in the central airways. The differentiation of bronchial carcinoid in a “typical or TC” variant and an “atypical or AC” variant is very important in terms of its clinical behavior and patients' outcome. 7–10 Surgical treatment of bronchial carcinoid has been accepted as the standard strategy, in which a limited resection by surgical bronchoplasty is recommended whenever feasible. 11–14 Long-term survival after radical surgery has been shown to be excellent, even in cases with nodal metastasis. 15 Survival analysis with special reference to the histology has shown that AC variant has a survival rate of 58.6%. 10 Survival is negatively influenced by atypical histology, in which the AC variant behaves like a small cell carcinoma. 9–11 A continuous spectrum of mitotic activity was seen in resected specimens of carcinoid tumors. 9 Increasing numbers of mitotic counts of neuroendocrine tumors indicate histology closer toward large-cell neuroendocrine carcinoma and small-cell carcinoma. However, it is also important to realize that accurate histology classification is not as easy as it may seem. 16 Agreement among pathologists is not 100%, although ultimately, a consensus agreement between experienced pathologists can be reached. The magnitude of microscopy magnification may depend on the type of microscope used. The thickness of the specimens may affect counting the exact number of mitoses. 9 Nevertheless, despite the fact that one cannot expect 100% accuracy for the typical histology, the classification of the TC variant is the most reproducible and the TC variant tends to be macroscopically endobronchial polypoid growing. STANDARD SURGICAL TREATMENT Ample data are available in the literature showing the excellent survival of patients with bronchial carcinoid. 11–15 Even for patients with nodal disease (mostly AC variant), complete tumor removal and mediastinal lymph nodes dissection may result in 5 year survival for more than 50% of them. The role of a more conservative resection, such as surgical bronchoplasty, bronchotomy, or local excision using Nd-YAG laser, 12,17 has also been addressed. Normal parenchyma-sparing surgical techniques have been accepted as the standard approach. Recurrences are mainly caused by the rather malignant behavior of the AC type. Survival of patients after incomplete resection locally or by surgery is strongly determined by the behavior of the AC variant, and patients with a TC variant may die because of an unrelated cause at a later stage 12,14,17; that is, clinical data show patients die of unrelated causes with TC despite incomplete resection, and they die of metastatic AC despite complete resection (radical surgery). It is also obvious that bronchoplastic surgery, such as bronchotomy, can only be carried out successfully when the tumor is small, with small pedicle or limited infiltration to the tracheobronchial wall, as well as being a TC variant. This is exactly the same subgroup of patients with intraluminal polypoid typical carcinoid located in the central airways who may be suitable for intraluminal bronchoscopic resection using bronchoscopic techniques such as excision biopsy, Nd-YAG laser, and electrocautery. One may argue that an intraluminal bronchoscopic approach is inappropriate because of the inability to assure radical removal and the inability to dissect mediastinal lymph nodes, in contrast to surgery. In addition, bronchoscopic approach may cause a delay, which may compromise the chance for a radical resection later on, owing to rapidly progressive tumor infiltration or the development of distant metastasis in time. However, for the TC variant, which grows very slowly, the endobronchial polypoid tumor may be initially removed by local bronchoscopic treatment. If this is incomplete, even in retrospect, very slow progression will occur and tumor will recur at a much later stage, after which surgical resection is still the choice of treatment, even in cases with mediastinal lymph node involvement. 15 Survival will remain excellent, even if surgery proved to be incomplete, as mentioned previously. 12,14 Besides, we currently have increasing ability to accurately monitor tumor growth by high-resolution computed tomography (HRCT) scan 18,19 and endobronchial ultrasound (EBUS). 20 It is unwise for a diligent bronchoscopist with the diagnostic tools currently available to allow a long delay before surgical resection while being active at the cutting edge of interventional bronchoscopy and being diligent in detecting early stage cancer. 1–3 An initial bronchoscopic approach is therefore justifiable. If the TC variant is clearly not completely removed by the IBT, either due to a technical reason, bronchial wall invasion, or insecurity about the distal tumor margin, surgical resection should follow without delay. 21,22 The time interval before the definite surgical resection may thus not pose a big problem after the initial IBT. One also has to remember that even after radical surgery of an AC variant, survival rate is still greater than 50%. Disease progression and ultimate prognosis is mainly determined by distant metastasis. Again, the extent of local resection either by surgery or IBT seems to be less relevant than the issue of accurate histologic classification. 11–15 Behavior of the AC type and its propensity to metastasize or to harbor occult metastasis at the time of presentation are clearly important determinants for cure. This is a comparable dilemma to dealing with lung cancer in general regarding our approach toward non-small-cell versus small-cell lung cancer. An AC variant is also unlikely to be a pedunculated or sessiled endobronchial polypoid tumor or located in the central airways without showing infiltration into the lung parenchyma. 7–10 This is apparent to an experienced bronchoscopist before IBT. A deliberate attempt at IBT by ignoring these bronchoscopic characteristics is obviously wrong. However, one may argue that minimal residual tumor in the bronchial wall can be so small that it is below the detection threshold of HRCT (≤2 mm) and EBUS (≤0.1 mm). 19,20 The clump of carcinoid cells accidentally left behind after IBT may prove to be an AC variant. This may cause a delay in treating patients properly, leading to a clinical dilemma such as in the case of a small cell carcinoma. The intraluminal specimen sampled during IBT might be improperly classified as the TC variant, showing no mitosis at all. However, this is unlikely, as neuroendocrine tumor tends to form homogeneous clumps of cells microscopically. The difficulty, however, lies more in the inability or unawareness of the individual pathologist to deal with the proper classification in cases of bronchial carcinoid, either using the Arrigoni criteria or the new classification by Travis et al. 8,9 Even if this may be true, it is still difficult to defend that the concept of “an initial bronchoscopic approach” is unacceptable. The argument that a delay of 6 to 8 weeks after IBT before the next bronchoscopic intervention may already have led to the development of distant metastasis is difficult to accept. The TC variant may show 5 to 10 mitoses per 2 mm2 (10 high power field) and may well be classified as an AC5–10 variant, but its 5-year survival rate is still 81%. 9 Experienced interventional bronchoscopists know what to look for and how to look at and deal with these intraluminal lesions, being diligently involved in early detection programs. 3 Centrally located carcinoid with endobronchial polypoid growth is therefore almost exclusively the TC variant, with relatively benign nature and showing a cure rate of 80% or more or other benign conditions such as hamartoma. The limitation of IBT for treating intraluminal tumor, pedunculated or sessiled, with limited invasion of the bronchial wall and our ability to use HRCT and EBUS for accurate assessment of local tumor infiltration are familiar issues for many interventional bronchoscopists. Data indicate that radiographically occult lung cancer can be treated with IBT as an alternative to surgical resection. 5,6,23 We must remember that the prognosis for incompletely resected squamous cell carcinoma is much worse than for incompletely resected bronchial carcinoid. Why are we then so reluctant regarding ITBC, insisting on “immediate surgical approach without delay”? Do we then really consider that several weeks' delay is unacceptable and risky while accepting that surgical bronchoplasty should be attempted in dealing with typical carcinoid? We currently perform the initial bronchoscopic approach under general anesthesia and use electrocautery for the treatment of ITBC. General anesthesia allows optimal control during tumor manipulation, for taking extensive biopsy specimens and preventing charring the tissue to minimize the chance for histologic misclassification and to provide the maximal amount of tissue available. Certainly for patients with endobronchial polypoid lesions, a bronchoscopist must be able to provide the pathologist with the largest piece of tumor without any difficulty. Improving the parenchymal condition distal to tumor obstruction (postobstructive pneumonia) is also warranted before surgery. Precision in taking biopsy and precision in applying electrocautery minimizes the scarring and damage to the bronchial wall. Electrocautery damage has been shown to be more superficial, 24 whereas Nd-YAG photons scatter deep in the target tissue, which may cause too extensive necrosis and scar formation. One should not hamper any future surgical attempt (e.g., surgical bronchoplasty or bronchotomy) that may be required if IBT fails in achieving the initial objective. 25 MANAGEMENT OF INTRALUMINAL BRONCHIAL CARCINOID We reported both in a retrospective and prospective study that IBT for ITBC has resulted in complete tumor eradication. 21,22 IBT may be an alternative for surgery in a subgroup of patients with ITBC. 22 The long-term outcome of 28 consecutive patients (16 men) in whom ITBC was initially treated with IBT has recently been analyzed. Between June 1991 and January 2000, 28 patients (16 men) who were referred with the possible diagnosis of ITBC have been entered in this study. All patients have been given full information about the purpose and the limitations of our study. Informed consent was obtained. Patients were included when tumor was accessible for the flexible bronchoscope. IBT under general anesthesia was then performed as the initial approach to evaluate intraluminal tumor mass for accurate staging. Tumor size never exceeded 2 cm in diameter. Extensive biopsy specimens were taken for repeat histologic examination to ensure the typical histology. When feasible, IBT was further applied for complete eradication of the intraluminal tumor mass to such an extent that it might enable a less extensive surgical resection. In case of an AC histology, any residual disease, or HRCT showing residual (extraluminal) disease, surgical resection was then carried out. Median age of the patients was 44 years (range 18–75). Table 1 shows the definite results of IBT strategy before any surgical attempt. Treatments applied were Nd-YAG laser or electrocautery. Apart from one mild stenosis during follow-up, there was no other complication. Especially, no significant bleeding occurred. In 16 patients (57% CI 43–79%) IBT was radical. Follow-up has been 6–103 months (median 47). One patient had extraluminal residual tumor behind the dorsal wall of the right mainstem bronchus (Fig. 1), but refused surgery. Gradual progression was seen after 3 years follow-up. In the other 12 (43%) patients, surgical removal was necessary, and all tumors were N0 stage. One patient proved to have an atypical carcinoid N0 disease. In another case, no residual carcinoid was found in the resected specimen. In 2 (18%) of the 11 cases of surgical resections, IBT enabled a less extensive surgical approach. Sleeve lobectomy was performed instead of pneumonectomy. The average duration of hospital stay was significantly longer in patients who underwent surgery (9 versus 3 days IBT). Average treatment costs, including admission charges, were USD $6,200 versus $2,500 for IBT. No patients in the IBT treated group had any regret that they were not subjected to thoracotomy. Analysis of the patients' perception regarding the thoracotomies and repeat bronchoscopies in the surgical group is currently under investigation.TABLE 1: Clinical data of patients with resectable ITBC ≤2 cm, initially treated with IBT with curative intent as an alternative to resectionFIG. 1.: A patient with residual extraluminal typical carcinoid after intraluminal bronchoscopic treatment of the intraluminal part. A gradual progression after 3 years is seen. No intraluminal recurrence was apparent on bronchoscopy or high-resolution computed tomography.CONCLUSION Intraluminal bronchoscopic treatment is a viable and cost-effective treatment alternative for surgery for selected patients with ITBC. The relatively benign nature of the typical bronchial carcinoid justifies a tissue conserving approach such as bronchoscopic surgery and surgical bronchoplasty. Our data showed that in a significant number of the patients IBT provided an elegant and less morbid initial approach than current standard of immediate surgery. In carefully selected patients, initial bronchoscopic treatment may enable a less extensive surgical resection. This is in accordance to current strategies to exploit the cutting edge of interventional bronchoscopy for adopting a parenchyma-saving approach whenever feasible. This strategy proved also to be cost-effective, offering the optimal quality of life for the patients involved without taking unacceptable risk. This new strategy can now be diligently used and is clearly an extension of our current approach to offer the most optimal presurgical condition before a definite resection is attempted.

Topic: Tracheal and airway disorders
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences