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Dr. Thurer is Professor of Surgery, Division of Cardiothoracic Surgery, University of Miami School of Medicine.
Correspondence to: Richard J. Thurer, MD, FCCP, Division of Cardiothoracic Surgery, University of Miami (R114), PO Box 016960, Miami, FL 22101-6960; e-mail: rthurer{at}mednet.med.miami.edy
Numerous endobronchial modalities are currently available for the treatment of bronchogenic carcinoma. These include laser therapy, photodynamic therapy, brachytherapy, airway stents, electrocoagulation, and cryotherapy. Each has its enthusiasts. Each has its advantages and disadvantages. In each case, there are patients who are ideal candidates for the modality and others who are less than ideal. Few institutions have available and are expert in the use of all or nearly all of the available techniques. Some are preferentially employed by surgeons, others by pulmonologists, radiation oncologists, and otolaryngologists. All modalities suffer from lack of convincing studies demonstrating their usefulness in varieties of clinical situations. It is difficult to compare patients across institutions and as described in various published studies. Each of the modalities has been accompanied by initial enthusiasm.
Endobronchial cryotherapy was initially reported in a number of publications between 1975 and 1983. It was then largely abandoned in favor of laser treatment, particularly in the United States. In France and Great Britain, interest has continued. There has been a modest increase in interest recently since the introduction and more general availability of small, flexible cryoprobes that can be passed through fiberoptic bronchoscopes. Current systems utilize nitrous oxide and are highly efficient.
Each endobronchial modality has its relative indications and contraindications. Cryotherapy is safe, with no danger of bronchial wall perforation, no radiation danger, no risk of electrical accidents or fires, and does not require laser training and certification. Disadvantages include delayed results and the requirement for multiple endoscopies to remove debris or to retreat. Laser therapy is immediate in its result but can be associated with bronchial or pulmonary artery injury and cannot effectively treat extrinsic compression. The initial equipment cost is substantial, and special training and certification is necessary. Electrosurgery is simple with apparent low risk, but is best applied to exophytic lesions. Newer fiberoptic systems appear easier to use and will likely be more effective than older systems using rigid instrumentation through rigid bronchoscopes. Stents of varying types are available and provide immediate results but can plug and migrate. Brachytherapy can treat submucosal and peribronchial lesions but the results are delayed, doses are limited, and complications such as fistula formation and pulmonary artery erosion can occur. Photodynamic therapy has recently been more widely used. Its results are delayed, there is a requirement for multiple bronchoscopies for debridement and possibly retreatment, and photosensitivity for a period of 30 days can be a problem. Recently available lasers appropriate for photodynamic therapy are more mobile and less costly than those available in the past.
Most lesions treated with cryotherapy are malignant, usually squamous cell or adenocarcinomas of the lung. Treatment is usually palliative, as is the case with most endobronchial therapies. Hemoptysis due to a visible lesion may be effectively controlled. Dyspnea due to obstructing lesions may be relieved, but the effect is delayed. Therefore, cryotherapy is generally inappropriate for management of acute airway obstruction, particularly when the trachea is involved.
Benign lesions such as granulation tissue and papillomas may be treated with cryotherapy. Some lesions, such as lipomas, are not amenable to cryosurgery since fat is relatively resistant to freezing. Lesions such as suspected carcinoid tumors might be frozen first to reduce the risk of hemorrhage during biopsy. Cryotherapy may be effective in treating airway strictures due to granulation tissue after lung transplantation as well as tracheobronchial obstruction.1 It can be useful in helping extract foreign bodies, clots, and mucus plugs.
Cryotherapy may be combined with other modalities such as radiation therapy and chemotherapy. There appears to be evidence of a favorable impact on subsequent radiation response when cryotherapy is used initially to debulk the lesion being treated. With the current interest in combined modality therapies utilizing chemotherapy, radiation therapy, and surgical resection, endobronchial therapy such as cryotherapy may well have a role in initial palliation of symptoms prior to surgical resection.
Currently, cryotherapy and other local endobronchial treatments are used almost exclusively for palliation and not with curative intent. Patients with resectable lesions are generally treated with endobronchial modalities if they are not fit for surgery. The article by Deygas and coworkers in this issue of CHEST (see page 26) best describes the use of cryotherapy with curative intent in early lesions: early superficial bronchogenic carcinoma. The described experience spans 12 years and is multi-institutional. This alone illustrates the problem of comparing series and evaluating results. Experience with endobronchial therapies suffers from lack of the ability to accumulate sufficient numbers of cases with similar characteristics over a reasonable period of time so as to be able to draw legitimate conclusions. This is of even more major importance when the treatment is directed at early stage disease and the attempt is curative rather that palliative in intent. In the experience described, the acknowledged "failure rate" is 20%. This is significant for lesions recognized at the earliest possible stage. These lesions should not be "undertreated," since long-term cure is the intent. Carcinoma in situ of the bronchus progresses to invasive carcinoma in the majority of cases,2 and must be treated initially with appropriately aggressive means. The dilemma is that many patients with carcinoma in situ or early superficial bronchogenic carcinoma have or have had lesions at multiple sites. This finding alone makes endobronchial therapy attractive. There is evidence, however, that local therapy resulting in destruction of the bronchial mucosa alone may not be curative in early cases since regeneration of the mucosa proceeds from submucosal glands that may harbor neoplastic cells after a variety of local ablative procedures.3
The issue of recurrence as a limitation on long-term survival may be addressed by intensive surveillance. This might allow recognition of recurrent or new lesions at a their earliest stage, allowing for reapplication of locally directed endobronchial therapy with hope of cure. The use of lung imaging fluorescence endoscopy in identifying lesions to be treated would likely provide additional benefit to long-term surveillance. Deygas et al do not discuss this type of posttreatment surveillance but do recognize the necessity for intensive follow-up of those patients treated. They do, however, present a comprehensive assessment of the current status of cryotherapy for early lesions, pointing out the significant advantages as well as the shortcomings of the method. Appropriate references are cited to support the use of this modality and to provide comparisons with other methods.
Cryosurgery in early lesions may well be effective. Confirmation of this will depend on carefully done systematic randomized trials with long-term follow-up, as noted by the authors of the report under discussion. Whether these trials will be possible remains open to question. Such trials would be required should be considered by various cooperative groups in an effort to answer the appropriate questions raised by the descriptive studies currently available.
References
This article has been cited by other articles:
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  M.-L. N. Huynh, K. C. Malcolm, C. Kotaru, J. A. Tilstra, J. Y. Westcott, V. A. Fadok, and S. E. Wenzel Defective Apoptotic Cell Phagocytosis Attenuates Prostaglandin E2 and 15-Hydroxyeicosatetraenoic Acid in Severe Asthma Alveolar Macrophages Am. J. Respir. Crit. Care Med., October 15, 2005; 172(8): 972 - 979. [Abstract] [Full Text] [PDF]
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 A K Banerjee, P H Rabbitts, and J George Lung cancer * 3: Fluorescence bronchoscopy: clinical dilemmas and research opportunities Thorax, March 1, 2003; 58(3): 266 - 271. [Abstract] [Full Text] [PDF]
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