Transoral laser microsurgery for laryngeal cancer: A primer and review of laser dosimetry
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Transoral laser microsurgery (TLM) is an emerging technique for the management of laryngeal and other head and neck malignancies. It is increasingly being used in place of traditional open surgery because of lower morbidity and improved organ preservation. Since the surgery is performed from the inside working outward as opposed to working from the outside in, there is less damage to the supporting structures that lie external to the tumor. Coupling the laser to a micromanipulator and a microscope allows precise tissue cutting and hemostasis; thereby improving visualization and precise ablation. The basic approach and principles of performing TLM, the devices currently in use, and the associated dosimetry parameters will be discussed. The benefits of using TLM over conventional surgery, common complications and the different settings used depending on the location of the tumor will also be discussed. Although the CO2 laser is the most versatile and the best-suited laser for TLM applications, a variety of lasers and different parameters are used in the treatment of laryngeal cancer. Improved instrumentation has lead to an increased utilization of TLM by head and neck cancer surgeons and has resulted in improved outcomes. Laser energy levels and spot size are adjusted to vary the precision of cutting and amount of hemostasis obtained.
KeywordsLaser Microsurgery Laryngeal cancer CO2 Endoscope
Over the last 50 years, advances in the management of laryngeal cancer have resulted in treatments with increased effectiveness as well as improved function. With the development of new conservation surgical techniques, advances in delivery of radiation treatments, and development of organ preservation regimens using chemotherapy (CT) combined with radiotherapy (RT), decision-making has become more complex.
Over the last 20 years, organ preservation surgery has evolved from standard external surgical approaches to resect cancer and preserve parts of the larynx to surgical procedures resecting equivalent tumors performed through an endoscope. These operations turn the operative paradigm “inside out”. They require re-learning the surgical anatomy from a new perspective, and development of skills to resect tumors through the lumen of long, narrow endoscopes. This has required critical examination and validation of oncological effectiveness of surgical resection, and surgeons learning a new skill set to successfully perform these procedures.
This review outlines the development of transoral laser microsurgery (TLM), provides rationale for treatment selection, describes a practical description of surgical technique, and analyzes technical factors associated with the use of the carbon dioxide laser in surgical management of laryngeal cancer.
Laryngeal cancer is the second most common cancer in the upper aerodigestive tract, with over 12,000 new cases a year in the United States and nearly 3,000 annual deaths . Approximately 95% of laryngeal cancers are squamous cell carcinomas (SCC), and a significant majority occur in patients between 60 and 70 years old . The overall 5-year survival rate for laryngeal SCC is 64% . The risk of developing laryngeal SCC has been closely related to tobacco and alcohol use, and is proportional to the amount and duration of use. Furthermore, tobacco and alcohol act synergistically [4, 5, 6, 7, 8]. Other potential risk factors for laryngeal SCC include laryngopharyngeal reflux [9, 10], as well as occupational exposure to asbestos and other environmental toxins. Because of confounding variables and low prevalence of most occupational exposures, definitive assessment is difficult and the contribution of these factors is debated [11, 12]. In recent years, a relationship between human papillomavirus (HPV) and head and neck cancer has been elucidated. Although the association is strongest for pharyngeal cancers, there appears to be at least a weak association with development of laryngeal cancer [13, 14, 15]. Genetic predisposition is also a contributing factor for the likelihood of developing HNSCC, partially explaining why some heavy smokers and drinkers fail to develop cancer, while some young persons with no significant exposure to tobacco, alcohol, or HPV exposure develop aggressive tumors .
Anatomy and staging
Head and neck cancer is also a heterogeneous disease, with different behavior and prognosis at each region of the head and neck, and within the larynx between the three subsites. Prognosis and treatment selection is dependent in large part on tumor staging using the TNM staging system of the American Joint Committee on Cancer (AJCC). Staging is based on the anatomical location of the tumor, tumor spread to the cervical lymph nodes, and distant metastasis. Using the TNM stage, patients are divided into four stage groups (I–IV), which provides a good stratification of survival probability and aids selection of appropriate treatment modalities. A full description of the staging system is provided in the AJCC staging manual .
Early stage cancer (stages I and II) is generally managed with single modality therapy, and treatment selection is based primarily on treatment morbidity as surgery and RT generally have similar cure rates. For advanced stage (stages III and IV) disease, combined modality therapies are generally used, and decisions regarding the ability to preserve the larynx are critical.
Endoscopic approaches to manage laryngeal cancer have developed over the last 30 years, and with increased anatomic understanding, clinical experience, and long-term results demonstrating oncological efficacy, transoral laser microsurgery (TLM) on the larynx has become an accepted treatment modality for both early laryngeal cancer, and as an organ preservation technique for advanced laryngeal cancers.
Overview of treatment options for laryngeal cancer
Total laryngectomy is performed for advanced laryngeal cancer, and is the gold standard oncologically. It is also debilitating, relegating recipients of this procedure to breathing through an artificial stoma in the neck, and learning alternative methods to speak without a voice box. Dissatisfaction with the morbidity of the total laryngectomy led to progressive development of conservation surgical procedures to remove portions of the larynx. For glottic tumors, removal of the vocal cord (cordectomy) and external vertical partial laryngectomy were developed to treat early glottic cancers. For supraglottic cancer, the supraglottic laryngectomy, which removes the epiglottis, preepiglottic space, and false vocal cords, was developed to preserve speech function and avoid a permanent stoma or tracheostomy [21, 22]. When contemplating conservation surgery, it is important to consider several basic concepts when evaluating if a patient is eligible for a conservation laryngectomy. It is critical to be able to accurately assess the complete tumor extent, and determine if the tumor can be resected with adequate oncologic margins and preserve the critical structures necessary for maintenance of laryngeal function to preserve the airway and maintain adequate phonatory function. The cricoarytenoid unit forms the basic functional unit of the larynx. Fundamentally, adequate laryngeal function requires preservation of at least, one functional cricoarytenoid joint, and the cricoid cartilage for the patient to be a candidate for conservation laryngectomy. .
Open conservation laryngeal resection (partial laryngectomy) is oncologically effective when performed on appropriately selected patients by competent surgeons. A limitation of open procedures is that intervening normal structures are either transected or resected to access the intraluminal tumor from an external approach. Open surgical approaches disrupt the strap muscles, laryngeal cartilages, nerves, and blood supply to tissues external to the tumor. This results in postoperative swelling necessitating temporary tracheostomy, impairment of laryngeal elevation, and loss of sensation, resulting in swallowing dysfunction and aspiration in the postoperative period. Chronic aspiration is the norm with open supraglottic laryngectomies. This limited the number of patients who were eligible for these procedures to those with good pulmonary function who could withstand several months of chronic aspiration while they heal and re-learn how to swallow. Open resection of glottic tumors results in postoperative airway swelling necessitating tracheostomy, either from the resection, or the soft tissue reconstructions designed to restore soft tissue removed during resection of the tumor. Because of the soft tissue disruption, airway stenosis from scarring and/or extensive atrophy resulting in aphonia are common and often lead to unpredictable functional outcomes. These limitations of traditional open conservation approaches led to efforts to develop endoscopic techniques to treat laryngeal cancers, described below.
Radiation therapy is an effective treatment for early laryngeal cancers. Treatment is performed daily over a 5–7 week period. It has the advantage of being a nonsurgical modality, and voice outcome for glottic cancer is generally very good. There are several limitations to primary RT. The primary limitation is RT generally cannot be repeated for curative purposes if there is recurrence, or a second primary in the previously radiated field . RT is often used with other treatment modalities. Postoperative RT is used in locally advanced laryngeal tumors to decrease recurrence . It is also used with CT in a variety of organ preservation regimens described below .
Photodynamic therapy (PDT) is a treatment modality that has demonstrated effectiveness, especially for superficial head and neck cancers. A light-activated pro-drug is administered, and it accumulates preferentially in cancer cells. The drug is activated by light of a specific wavelength catalyzing reactions that result in release of oxygen free radicals that are cytotoxic to the cells accumulating the drug. PDT produces a variable length of photosensitivity following treatment that is dependent on the agent used. Although impressive results have been reported [27, 28], the technique is not yet widely available.
Organ preservation strategies
In 1991, the Department of Veterans Affairs Laryngeal Cancer Study Group published a landmark randomized controlled clinical trial comparing an organ preservation protocol with total laryngectomy. Induction CT followed by RT in clinical responders in carefully selected laryngeal cancer patients produced an equivalent cure rate to those patients receiving TL, while preserving the larynx in approximately two-thirds of cases . This trial demonstrated the oncologic viability of organ preservation of the larynx, and launched a new trend for organ preservation in selected advanced laryngeal cancers. In 2003, the Radiation Therapy Oncology Group and the Head and Neck Intergroup published a trial (RTOG 91-11) that confirmed that the use of concurrent chemoradiation therapy (CRT) significantly improved locoregional control and organ preservation compared to CT followed by adjuvant RT or RT alone , making concurrent CRT a new organ preservation treatment standard for selected advanced laryngeal cancers. Subjects receiving radiation alone did not fare as well as either the concomitant or neoadjuvant CT groups. This study excluded advanced T4 lesions with cartilage invasion or extralaryngeal spread . Since the introduction of organ preservation strategies, the indication for radical surgery, a total laryngectomy (TL), has declined. The combination of CT and RT is a very aggressive treatment regimen. Mortality of up to 4% has been reported in major series . Many patients undergoing these treatments experience prolonged loss of swallowing function, and in a minority of patients, long-term fibrosis results in anatomic preservation of a nonfunctional larynx. TL is indicated when the disease cannot be treated with partial laryngectomy, CT or RT, or when the laryngeal tumor has invaded extralaryngeal tissues of the neck .
Transoral laser microsurgery (TLM) for laryngeal cancer
What is TLM?
Transoral laser microresection, in laryngeal cancer is the oncologic resection of tumors performed through an endoscopic as opposed to an external surgical approach. Tumors are visualized through an endoscope, resected using lasers or other cutting and coagulation methods, and the wound bed is left open to heal by secondary intention.
The historical evolution of TLM for laryngeal cancer goes all the way back to the early days of laryngeal surgery. Chevalier Jackson was perhaps the first to endoscopically resect a tumor of the epiglottis through an endoscope with cup forceps in 1915 [33, 34]. Because of very primitive equipment, the ability to perform transoral resections of tumors was limited, and tumor resections of the larynx were only occasionally performed.
As laryngology developed, technological advances laid the groundwork to allow endoscopic surgical resections. The first advance was the development of fiber-optic light sources, to allow distal illumination of the airways. A second important advance was the development and use of the operative microscope, which allowed magnified views of the larynx. In conjunction with magnification was the development of smaller instruments adapted from otologic instruments to manipulate tissues within the larynx. The critical advance that allowed transoral laser microsurgery to develop was coupling of the newly developed carbon dioxide laser to the microscope and developing micromanipulators to precisely deliver energy to the larynx. In 1972, Strong and Jako  coupled a CO2 laser to a surgical microscope for use through a laryngoscope, introducing a new modality for the treatment of benign laryngeal pathologies. Three years later, in 1975, Strong  used the CO2 laser to successfully treat 11 patients with early T1 laryngeal cancer. In 1978, Vaughan  first reported the use of the CO2 laser to resect supraglottic tumors. Based on the early work by Strong and Vaughan, Steiner [38, 39, 40, 41] worked to develop new endoscopes to aid exposure, developed sturdy instruments to grasp and retract the larynx, worked out techniques to obtain and maintain hemostasis through the endoscope, and importantly demonstrated that tumors could be resected in sections with oncologic safety. Importantly, these techniques have been adapted by others [42, 43, 44, 45, 46, 47, 48], and the oncologic effectiveness has been replicated, treating different stages and locations of laryngeal cancer.
Indications and contraindications for TLM in malignant lesions
• Tumors amenable to conservation laryngeal surgery T1, T2, and selected T3 tumors
• Ability to adequately expose the larynx
• Palliative tumor debulking
• Extensive tumors
○ Extralaryngeal tumor spread
○ Inability to preserve cricoid and one arytenoid
• Inadequate endoscopic access
The CO2 laser has an infrared beam with a wavelength of 10.6 μm. It is delivered into the airway along the axis of the microscope visual field using a micromanipulator coupled to the microscope. The micromanipulator allows precise control of beam delivery to precisely cut through tissues and obtain hemostasis. The carbon dioxide laser has ideal tissue properties for surgery in the larynx because of its high coefficient of extinction in water, which limits soft tissue penetration and minimizes collateral thermal effects, while providing generally adequate hemostasis. Recently, laser delivery through a flexible hollow tube has become available to deliver the laser beam close to the target. The advantage of the flexible systems is the ability to have limited bending of the fiber within the endoscope to vary the angle of attack for cutting through tissues and to allow easier access to some areas that are difficult to reach with traditional laser systems. The primary limitations of these systems are limited angulation and as with use of standard microlaryngeal instruments, the effect of natural surgeon tremor is magnified along the shaft of the instrument [50, 51].
Although the CO2 laser was the first to be used in the larynx, a number of other lasers have been used within the larynx. They differ in method of delivery of the energy, tissue penetration, and tissue cutting and hemostatic capabilities. The KTP (532 nm) laser has excellent hemostatic properties with a slight increase in the depth of tissue injury. It is delivered through a quartz fiber, which for selected tumors can be advantageous. Recently, pulsed KTP lasers have become available for tissue photoablation. For premalignant lesions, and selected early glottic carcinomas, experience with 585- and 595-nm pulsed dye lasers has been reported [48, 52]. Other lasers, including thulium and gold lasers, have recently become available and are being evaluated [53, 54, 55].
Small tumors (e.g., small superficial T1 glottic tumor) can be resected en bloc by cutting around the tumor and removing it in one piece. Another option for small tumors, especially if the tumor is more infiltrating is to cut the tumor in half to definitively establish depth of invasion and then remove it in two pieces. For larger tumors, en bloc resection is either challenging or impossible. For larger tumors, the tumor is removed in sections starting at one end of the tumor, working systematically across the tumor to completely resect the tumor. This technique initially came under significant criticism because it violated classic Halstedian principles of en bloc resection. Extensive study by Steiner [39, 57] and others [45, 58, 59, 60] has demonstrated that there is no sacrifice of oncologic control using a block-wise resection of the tumor in discrete segments.
An advantage of removing the tumor in sections is the ability to precisely define the depth of tumor invasion. A significant risk of en bloc resections is the inability to determine the depth of tumor penetration, and there is a risk of unknowingly resecting too close to the tumor margin at the deepest and least accessible portion of the tumor. By cutting directly through the tumor under high magnification, the depth of tumor penetration can be seen and appropriate deep margins delineated.
Once the larynx is exposed and the tumor and surrounding structures are visualized, the surgeon marks the peripheral margins using the CO2 laser. The size of the margin depends on the location and stage of the tumor and if the patient is undergoing primary treatment or resection of recurrent disease. If there has been prior RT, wider margins are taken because of the higher risk of an infiltrative pattern of spread through the tissues. For small glottic tumors, a margin of as little as 1 mm is necessary. For deep margins, several millimeters, and ideally a connective tissue barrier are chosen for margins of resection.
Successful resection of tumors requires the laser to perform a variety of tasks from tissue ablation, precise cutting, and coagulation of tissues. These tasks require different techniques and differing laser energies, spot sizes, and pulse modes. It is important to emphasize that for a given application, there are no fixed settings, and that practice patterns vary significantly by physician. Several laser parameters are selected for each particular case, including: (a) power, (b) spot size, (c) exposure time, and (d) power (pulse) delivery. Laser energy can be delivered through intermittent pulses, repeated pulses, continuous wave (CW), or use of very rapid (millisecond) pulse delivery in the form of ultrapulse or superpulse mode.
CW mode produces surrounding tissue damage from thermal spread of the laser energy. In order to produce adequate cutting and hemostasis with limited char formation and thermal spread, alternative pulse delivery modes have been developed to allow tissue cutting and hemostasis while limiting thermal damage to surrounding tissues. By producing high-energy, short-duration pulses in rapid succession, tissue ablation can occur with limited heat damage to surrounding tissues. The two most common modes, ultrapulse and superpulse, utilize slightly different strategies to produce rapidly pulsed waves that incorporate high peak power delivered in millisecond pulses. Superpulse mode delivers short bursts (less than 1 ms) in rapid succession. The energy profile of the beam is characterized by a high initial peak energy spike with rapid drop in energy over duration of the pulse. The ultrapulse mode delivers a short pulse with a rapid peak onset, relatively constant energy delivery for the duration of the pulse, and rapid decline in power at the end of the pulse, approximating a square wave. The superpulse mode has higher peak energy but less total energy delivery per pulse and more rapid pulse delivery, while ultrapulse mode has lower peak energy in each pulse, higher energy delivered with each pulse, and longer duration between pulses [61, 62]. From a practical standpoint, the clinical differences between the two pulse modes is subtle, although the thermal damage from the superpulse mode is reported to be slightly greater than with utrapulse mode than the superpulse mode .
When cutting through gross tumor it is necessary to increase the power as high as 20 W and with a beam diameter as low as 400 μm, using a continuous wave pulse to rapidly penetrate the tumor and have adequate hemostasis.
Utilize traction and counter traction to place tissues on tension. As the laser cuts through the tissues, they separate; exposing underlying structures and this also produces decreased char formation.
When dissecting near large vessels or nerves, it is important to decrease power, defocus the beam to increase spot size, and utilize conventional dissection techniques to expose vessels and nerves.
For small- to intermediate-size vessels (up to approximately 1 mm), improved hemostasis is achieved using a defocused beam with increased power.
Large vessels will not be handled adequately with the laser. Liberal use of hemostatic clips, bipolar cautery, or monopolar cautery is recommended for medium- to larger-sized vessels.
- Ultrapulse and superpulse modes are generally used to define margins, cut through normal tissues, and to perform precise tissue dissection. They produce less surrounding damage and char formation, which results in better anatomic visualization. Decreasing the peak pulse energy results in decreased penetration with each pulse and is useful for fine dissections.
○ Ultrapulse and superpulse modes are also helpful for cutting through bone or cartilage when used with high power settings.
Postoperative care and feeding
The postoperative care regimen of the patient is tailored to the extent of the resection. The two most critical concerns are postoperative bleeding into the airway, and airway obstruction from edema. Thus, for larger resections or those involving the supraglottis, the patient is initially managed in the ICU. After 48 h, the risk of major bleeding is significantly decreased, although there can be delayed hemorrhage from sloughing of eschar after 7–10 days. If there is significant bleeding, securing the airway through intubation, or if necessary, tracheostomy is of primary concern to prevent drowning from aspirated blood.
Once the patient is awake and stable, oral alimentation with ice chips and water is started. This clears secretions and inflammatory materials, and helps keep the wound bed clean. Diet is advanced as tolerated. Decisions regarding oral alimentation rest on the extent of the resection, and patient factors. If the patient is expected to have compromised swallowing based on age, preoperative swallowing function, mental status, or prior radiotherapy, a nasogastric feeding tube is placed and swallowing evaluations are obtained. Antibiotics to cover oral flora are given for 24 h, and surgical practices vary, with some practitioners stopping at 24 h, and others providing more extended coverage after discharge because of the large open wound in a contaminated field.
The final pathologic findings and margin status are reviewed carefully to ensure complete tumor eradication. If there are positive or close margins, the location is determined based on review of the specimens with anatomic maps of the resection. A second procedure to remove focal areas where there are close or positive margins is performed. Depending on the oncological stage, the likelihood of need for a second resection ranges from as low as 5% in early glottic carcinoma to up to 29% in advance tumors, to definitively clear close or positive margins [57, 63, 64, 65].
In general, TLM is well tolerated with low complication rates, and generally improved functional outcome compared to corresponding open procedures resecting the same size tumor. Early postoperative hemorrhage (described above) is a potentially lethal complication. Often there will be a small amount of bleeding, but significant bleeding from a major artery in the larynx can result in aspiration of blood into the airway. It is critical in this situation to secure the airway, either by endotracheal intubation or by performing a tracheostomy, followed by operative control of hemorrhage. Airway obstruction is uncommon, as resection of the tumor generally provides an airway that is more widely patent following surgery. Since the neck is not incised, there is much less postoperative swelling and edema that characterizes open surgical procedures on the larynx. However, prolonged tongue retraction and compression during long operations can result in soft tissue ischemia, and in tongue edema postoperatively. Additionally, prolonged displacement of the tongue by the laryngoscope can cause temporary lingual or hypoglossal paresis. In cases lasting more than 1–2 h, periodically releasing suspension to allow blood flow to the tongue markedly decreases the likelihood of developing postoperative tongue swelling or nerve dysfunction. The neuropathy caused by retraction is temporary, and generally resolves over several weeks. Also mentioned under postoperative care, aspiration can be caused by extensive resection, preexisting laryngeal impairment, advanced age or poor health. Preoperative and postoperative assessment to determine the risk for aspiration is necessary to prevent development of aspiration pneumonia. Other complications encountered include: mucosal burns of the lips, oral cavity or oropharynx, dental injuries (loosened or chipped teeth), infection, dysphagia, and airway fires or burns [66, 67, 68, 69, 70, 71].
TLM is an emerging technique for the treatment of laryngeal cancer and other head and neck cancers. Although several lasers may be used, most consider the CO2 laser the most versatile laser for the great majority of applications. Technological advances in microscope design, lasers, surgical instruments, energy beam profile, and delivery systems have made resection of tumors through the endoscope possible. Demonstration that tissues could be resected in a logical stepwise progression to systematically clear the field of tumor with oncologic margins eliminated the need to attempt “en bloc” removal. This expanded the extent of resections that can be safely performed. With new technology and new surgical techniques, incorporation of TLM into the surgical armamentarium requires commitment to learn the technically challenging procedures, and institutional commitment of resources to purchase necessary equipment to perform these procedures. Careful study of outcomes by Steiner and others [24, 38, 39, 40, 41, 57] have demonstrated improved functional outcome with at least equal oncologic outcome. This has resulted in gradual but progressive expansion of the techniques globally.
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