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J Thorac Cardiovasc Surg 1998;116:402-406
© 1998 Mosby, Inc.

General Thoracic Surgery

Bronchoscopic treatment of intraluminal typical carcinoid: a pilotstudy

From the Departments of Pulmonary Medicine and Surgery, Free UniversityHospital Amsterdam, The Netherlands.

Received for publication Nov 4, 1997. Revisions requested Jan 6, 1998; revisions received May 15, 1998. Accepted for publication May 18, 1998 Address for reprints: G. Sutedja, MD, PhD, FCCP, Department ofPulmonary Medicine, Free University Hospital, PO Box 7057, 1007 MB Amsterdam,The Netherlands

	Abstract

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Objective: The curative potential ofvarious bronchoscopic treatments such as Nd:YAG laser, photodynamic therapy, andbrachytherapy for the treatment of intraluminal tumor has been reportedpreviously. Bronchoscopic treatment can be used to treat small intraluminaltumor with curative intent, such as in patients with roentgenologically occultsquamous cell cancer. In a retrospective study, we showed that bronchoscopictreatment provided excellent local control with surgical proof of cure in 6 of11 patients with intraluminal typical bronchial carcinoid.
Methods: In a prospective study, 19 patients (8 women and11 men) with resectable intraluminal typical bronchial carcinoid have undergonebronchoscopic treatment under general anesthesia. Median age was 44 years(range, 20-74 years). If tumor persisted after 2 bronchoscopic treatmentsessions, surgery was performed within 4 months after the treatment.
Results: Bronchoscopic treatment was able to completelyeradicate tumor in 14 of the 19 patients (complete response rate 73%, 95%CI: 49%-91%). Median follow-up of these patients is 29 months(range, 8-62 months). One patient had severe cicatricial stenosis afterbronchoscopic treatment, and sleeve lobectomy was necessary. No residualcarcinoid was found in the resected specimen. In the remaining 5 patients,bronchoscopic treatment did not result in a complete response and radicalsurgical resection was performed afterward with confirmation of residualcarcinoid in the resected specimen. Median follow-up of the surgical group is 34months (range, 12-62 months).
Conclusions:Current data suggest that bronchoscopic treatment may be an effectivealternative to surgical resection in a subgroup of patients with resectableintraluminal typical bronchial carcinoid. It alleviated the necessity ofsurgical resection in 68% (95% CI: 43%-87%) of thepatients.

	Introduction

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Many bronchoscopic techniques are currently available for the treatmentof patients with tracheobronchial malignant tumors. ^1,2In patients with roentgenologically occult intraluminal tumor, bronchoscopictherapy with curative intent, especially photodynamic therapy, may provide analternative to surgery. ^3-7

Surgical resection is the treatment of choice in patients with bronchialcarcinoid and survival has been shown to be excellent. In patients with typicalbronchial carcinoid, even limited surgery, such as bronchoplastic surgery, hasbecome an accepted treatment modality. ^8-11 Until recently, bronchoscopictreatment was considered only in patients with contraindications for surgicalresection. ¹² Preoperativebronchoscopic treatment enabled better assessment of tumor growth and restoredairway patency to improve the preoperative pulmonary condition in patients withobstructive pneumonia.

We ¹³ reportedpreviously that bronchoscopic treatment resulted in histologically confirmeddisappearance of tumor in patients with intraluminal typical bronchial carcinoidwho underwent surgery after bronchoscopic treatment. Bronchoscopic treatment mayprovide a parenchyma-sparing treatment alternative for bronchoplastic surgery.This seems to be justified by the excellent survival of patients with typicalcarcinoid after bronchoplastic surgery, the low rate of lymph node invasion andmetastasis, its central localization, its tendency for endobronchial polypoidgrowth, without extraluminal extension, and the feasibility of using currentbronchoscopic treatment techniques to obtain tumor necrosis extending severalmillimeters deep. We therefore conducted a prospective study of bronchoscopictreatment, using Nd:YAG laser or bronchoscopic electrocautery, in carefullyselected patients with resectable intraluminal typical bronchial carcinoid, withthe purpose of complete tumor eradication, as an alternative for surgicalresection.

	Methods

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Patients were selected from consecutive patients referred to our clinicbecause of intraluminal typical bronchial carcinoid. Inclusion criteria wereaccessibility of tumor for the fiberoptic bronchoscope and high-resolutioncomputed tomographic (CT) scans showing no signs of bronchial wall infiltration(bronchial wall irregularities, bronchial wall thickening, peribronchial tumorinvasion), or enlarged lymph nodes. Scan technique used for high-resolution CTwas previously described. ¹⁴Bronchoscopic treatment was performed by means of high jet ventilation with thepatient under general anesthesia. Nd:YAG laser and bronchoscopic electrocauterywith both the rigid and fiberoptic bronchoscopes were used to provide optimalmanagement in clearing intraluminal tumor mass. ¹⁵ In case of bronchoscopicelectrocautery, the same technique has been used as described previously. ¹⁶ Carcinoids were documentedphotographically before and immediately after treatment. Follow-up bronchoscopicexamination was performed to assess response 4 to 6 weeks after bronchoscopictreatment. In case tumor persisted after 2 bronchoscopic treatment sessions,surgical resection was performed.

Oral informed consent was obtained from all subjects. Beforebronchoscopic treatment, there was always a consensus about treatment strategybetween the surgical oncologist and the pulmonologist. This study was approvedby the scientific and ethical board of our hospital.

	Results

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So far, 19 patients (8 women and 11 men), median age 44 years, range 20to 74 years, have been treated. Bronchoscopic findings before bronchoscopictreatment with regard to localization, estimated tumor size, and visibility ofdistal tumor margin are shown in Table I. Technique used and result of bronchoscopic treatmentare also shown in Table I. No complications occurred duringbronchoscopic treatment, and no significant bleeding occurred. The use of Nd:YAGlaser or bronchoscopic electrocautery under general anesthesia provided anoptimal treatment setting to control hemorrhage. Follow-up data includingtreatment management of those not obtaining a complete response despite 2bronchoscopic treatment sessions are also shown in Table I.

Overall, the complete response rate after bronchoscopic treatment was 74%(95% CI: 49%-91%), and 68% (95% CI: 43%-87%)of the patients were spared surgery. During follow-up, bronchoscopic examinationwas performed at a 3- to 4-month interval. Median follow-up of patients afterbronchoscopic treatment has been 29 months (range, 8-62 months). Surgicalpatients had a median follow-up of 34 months (range, 12-62). These patients didnot undergo regular bronchoscopic examination except once after resection,because surgical resection was radical.

	Discussion

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This prospective study was started after our retrospective data showedthat bronchoscopic treatment may provide complete tumor eradication in asubgroup of patients with intraluminal typical bronchial carcinoid. Theircarcinoid seemed not to be the tip of an iceberg. ¹⁶ Currently, several bronchoscopictreatment alternatives are available for palliation in patients with obstructivetracheobronchial malignant tumors. ^1,2 These techniques have been used tocompletely eradicate intraluminal tumor, and their curative potential formultiple, occult cancers and carcinoma in situ has been established. ^3,7,17,18The indication and limitation of bronchoscopic therapy has been addressedrecently. ¹⁹ The success rateof bronchoscopic treatment with curative intent depends on the malignantbehavior of the tumor. Patients with occult cancer 3 mm thick or less and with alongitudinal axis of 20 mm or less have been shown not to have lymph nodemetastasis. ^20,21 Therefore photodynamic therapyhas been proposed as a "normal tissue-sparing" treatment alternativefor surgical resection, partly on the basis of the issue of photodynamic therapyselectivity. ^5,22 However, data to support thisdrug selectivity are lacking, and skin photosensitivity remains a problem. ^23,24Randomized trials comparing the different bronchoscopic treatment techniques arenot available. It is, however, fair to ask whether the technique per se is themost important determinant for cure. ¹⁹Early stage cancers several millimeters thick require necrosis of severalmillimeters regardless of the technique of choice.

We presumed that the same may apply for the selected patients withintraluminal typical bronchial carcinoid in whom the relatively benign nature ofthe disease justified bronchoplastic surgery. Previous surgical series haveshown that bronchoplastic surgery is indeed an acceptable treatment strategy inpatients with intraluminal or mural, pedunculated or sessile typical carcinoidof limited size. ^9-11

As shown in our present series, tumors were intraluminal and neverexceeded 2 cm in diameter. High-resolution CT scan did not show grossperibronchial tumor involvement. ¹⁴In depth necrosis of several millimeters is sufficient to completely eradicatethese tumors. We used both ND:YAG laser and electrocautery to achieve this. Inour clinical experience no difference was found between these techniques withregard to tumor clearance. ¹⁶Intraluminal typical bronchial carcinoid localizations may be such that surgicalbronchoplasty is not always feasible, resulting in a relatively wastefulparenchymal surgical resection, while the "preservation of as much normallung tissue as possible is one of the primary goals of therapy." ²⁵ Previous series also show thatparenchyma-sparing resection yields excellent survival. ^9-11,26 Typical carcinoid behavesdifferently from the atypical variant, with excellent survival after completesurgical resection despite the presence of metastasis in lymph nodes. ^8,27It is therefore understandable that patients suitable for bronchoplastic surgerymight be excellent candidates for bronchoscopic treatment. Our series shows thatmural type carcinoid was not necessarily the tip of an iceberg and that indeedthe findings of high-resolution CT are correlated to complete response. We havemore difficulties, however, in treating intraluminal typical bronchial carcinoidextending to the segmental bronchi, where the distal tumor margin was invisiblefor the bronchoscopist. In patients 5, 8, 11, 13, and 15, tumor was located in asegmental bronchus of the left or right upper lobe, and the distal involvementof carcinoid was difficult to assess during and after bronchoscopic treatment.In retrospect, it was therefore not surprising that bronchoscopic treatment didnot result in complete tumor eradication and that salvage surgery was necessary.Therefore it seems that patients with intraluminal typical bronchial carcinoidin whom distal tumor margin is less clear are not candidates for bronchoscopictreatment. This is a problem similar to treatment of occult squamous cell lungcancer and shows the limitation of bronchoscopic treatment in general. ^1-4,19 It is of interest that inpatient 8, repeated thin-section CT scans revealed an enlarged hilar node afterthe first bronchoscopic treatment had resolved the atelectasis. Transbronchialneedle aspiration showed carcinoid cells in the hilar node, and the patientunderwent surgical resection. In patient 11, complete response could not beobtained despite repeated bronchoscopic treatment, and in the resected specimenatypical carcinoid was found with a diseased hilar node. This particular case isa warning that bronchoscopic treatment as the initial therapy for patients withresectable intraluminal typical bronchial carcinoid may have a certain risk.However, the use of general anesthesia in combination with techniques thatprovide excellent coagulation enables the bronchoscopists to collectrepresentative biopsy specimens for histologic examination. Still, definitehistologic classification is sometimes possible only after a complete surgicalresection.

In conclusion, bronchoscopic treatment seems to be an effective initialtreatment alternative for patients with resectable intraluminal typicalcarcinoid. This prospective study supports our earlier experience ¹³ that patients with intraluminaltypical bronchial carcinoid may be given bronchoscopic treatment after a carefulselection has been made. These selection criteria are good bronchoscopic tumoraccessibility with clearly visible distal tumor margin and high-resolution CTscans showing no extraluminal tumor extension. Bronchoscopic treatment mayoptimize the parenchyma-conserving treatment strategy in patients withintraluminal typical bronchial carcinoid. ^9-11 A less extensive surgicalresection may also be possible after preoperative bronchoscopic treatment.Surgery can be performed afterward in case of persistent or residual tumor.Longer follow-up will reveal whether bronchoscopic treatment is as effective asbronchoplastic surgery in a subgroup of patients with resectable intraluminaltypical bronchial carcinoid.

	References

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