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Keywords:

  • Long-term results;
  • complications;
  • conventional surgery;
  • radiotherapy;
  • transoral laser surgery.

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. BIBLIOGRAPHY

Objectives/Hypothesis In carcinoma in situ (CIS) tumors malignant cells have not penetrated the basement membrane and therefore have no metastatic potential. Treatment strategies of CIS are topics of ongoing discussion. The aim of this study was to evaluate long-term results of CO2 laser therapy in laryngeal CIS.

Methods From 1986 to 1995, 29 patients with glottic CIS with a minimum follow-up of 2 years were treated initially with transoral CO2 laser surgery and were included is this series.

Results A complete removal of the tumor was possible with superficial laser cordectomy in 21 patients and with subligamental laser cordectomy in 8 cases. There was no tumor-related death in this series. Repeated laser resections were performed in four patients for local recurrences. No patient required total laryngectomy or radiotherapy during a follow-up ranging from 25 to 143 months.

Conclusions Local control rates presented in this study are superior to those previously reported with conventional surgery and similar to those after radiotherapy. The ultimate rate of larynx preservation was seven times higher than reported after radiotherapy. Our results add further support to the observation that laser surgery is the best treatment option for CIS of the larynx. Based on the material of this study, recommended treatment for CIS is CO2 laser resection in combination with a meticulous follow-up for early recognition of local recurrence.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. BIBLIOGRAPHY

Carcinoma in situ (CIS), first described by Broders 1 in 1932, is a peculiar problem to those involved in diagnosis and treatment of this lesion. Average annual incidence rates of upper aerodigestive tract CIS increased from 1.5 to 3.1 lesions per 100,000 person-years between 1935 and 1984. 2

Carcinoma in situ may develop in any mucosal surface of the upper airway. 3 The glottic region of the larynx is the preferential location, probably because these lesions are only infrequently detected in the supraglottis and hypopharynx before they progress to infiltrating carcinoma. 4,5 Clinically, CIS presents along a continuum from a limited lesion to the more extensive tumor involving both cords without cord fixation. 6 Histological examinations show severe atypical epithelial cells that have not penetrated the basement membrane and therefore have no metastatic potential. 3 Based on microscopic findings, difficulties are encountered in separating CIS from microinvasive carcinoma or “superficial extending” carcinoma summed up as “early” laryngeal cancer, particularly in small biopsy specimens of mucosal tissue. 7 Immunohistological investigations of epidermal growth factor receptors have been helpful in distinguishing moderate from severe dysplasia. 8

Carcinoma in situ has mostly been treated with radiotherapy. 9,10 The multifocal appearance of the lesions and excellent preservation of voice are the main reasons to prefer radiotherapy over surgery. However, the risk for local recurrences or even progression to infiltrating squamous cell carcinoma is high with this therapeutic approach. Therefore management strategies of these neoplasms are topics of ongoing discussion. In recent years, encouraging results have been reported for the minimally invasive surgical approach using microlaryngoscopic removal of the diseased mucosa with the help of surgical lasers. 11–15 However, only insufficient data on long-term results of transoral laser surgery have been reported in the literature, particularly on ultimate rates of laryngeal preservation. 10

The aims of the present study were to evaluate the long-term results of CO2 laser surgery for the treatment of CIS of the larynx at the Department of Oto-Rhino-Laryngology of the University of Cologne, to compare these data with those reported in the recent literature concerning radiation therapy and surgical approaches, and to establish indications for laser surgery in this laryngeal lesion.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. BIBLIOGRAPHY

The tumor registry of the Department of Oto-Rhino-Laryngology of the University of Cologne was reviewed to identify patients who presented with CIS of the larynx and were treated with transoral laser surgery from January 1, 1986 to December 31, 1995. All charts could be retrieved and contained detailed data of tumor staging, therapy, and outcome for retrospective analysis.

Inclusion criteria for this study were that tumors were restricted to the epithelium without transgression of the basement membrane, that transoral laser surgery was the initial treatment modality, and that minimum follow-up was not shorter in duration than 2 years.

Twenty-nine patients presenting with glottic primaries fulfilled these criteria and were included in this series. The clinical data for these patients are demonstrated in Table I. Of these 29 patients, 26 were cigarette smokers at the time of diagnosis or had stopped smoking up to 2 years earlier. One patient had given up smoking 13 years earlier, and two patients had never smoked.

Table Table 1.. Carcinoma in Situ of the Larynx: Clinical Data and Outcome of 29 Patients Treated With Superficial Laser Cordectomy.
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Nine cases were excluded from our series. In two of them laser surgery has been performed as surgical salvage after failure of initial conventional decortication or radiation therapy; follow-up was less than 2 years in two patients; and histological re-examination of five tumors revealed microinvasion of the underlining basement membrane.

Surgical Technique

Transoral surgery was performed with a CO2 laser (different models supplied by Laser Sonics (Milpitas, CA) and Sharplan (Tel Aviv, Israel). The surgical laser was always coupled to a Zeiss (Carl Zeiss, Thornwood, NY) operating microscope and was generally set to an output power of 2 to 3 W in the superpulse mode at a spot size of approximately 0.5 to 0.8 mm2. All patients had transoral intubation for surgery. Different laryngoscopes, including bivalved adjustable laryngoscopes as described by Steiner 15 were used to expose the larynx. The extent of surgical procedures performed in patients of this series was classified according to the proposal for endoscopic cordectomy of the European Laryngologic Society. 16 Small mucosal lesions that did not touch the anterior commissure were frequently removed as excisional biopsy specimens with margins. In these cases, the procedure was diagnostic and therapeutic at the same time. Biopsy of more extended lesions and lesions reaching the anterior commissure was performed during a first intervention, and surgery was performed after histological confirmation of the diagnosis.

Submucosal cordectomy.

Submucosal cordectomy is the resection of the epithelium, passing through the superficial layer of the lamina propria. This surgical procedure spares the deeper layers and thus the vocal ligament (Fig. 1, left vocal cord). This procedure is similar to vocal cord stripping with cold instruments.

Subligamental cordectomy.

Subligamental cordectomy is the resection of the epithelium, Reinke's space, and the vocal ligament. Subligamental cordectomy is performed by cutting between the vocal ligament and the vocal muscle. The vocal muscle is preserved as much as possible (Fig. 1, right vocal cord). The resection may extend from the vocal process to the anterior commissure.

The resected specimens were mounted to a cork plate and anatomically marked according to the excision area for pathological workup.

Lesions at the anterior commissure were frequently treated in two separate interventions. One side was treated during the first intervention, and the opposite side during a second procedure that was staged for 3 to 4 weeks to allow for complete epithelialization of the initial wound. A planned second procedure was considered in cases that were believed to be at risk for the formation of an anterior web (i.e., when the free edge of the vocal cord was affected bilaterally in the anterior commissure region).

Follow-up

Microlaryngoscopic examination under general anesthesia with multiple biopsies was performed 12 weeks after the resection to confirm complete remission histologically. Patients were then advised to see a laryngologist on a regular basis every 3 months for flexible fiberscopic examination or rigid telescopic laryngoscopy for at least 5 years after the initial diagnosis, or to have such follow-up examinations performed at the department's outpatient service in identical intervals. All patients were informed that smoking is the most important risk factor for laryngeal carcinoma, and all were strongly advised to give up smoking. No additional dietary recommendations (e.g., vitamin supplementation or retinoic acid therapy) were given. No systematic data on reflux symptoms were available in our charts, because many of the patients in this series were treated before reflux was identified as an additional risk factor for chronic laryngeal inflammation and possibly dysplastic transformation.

Voice Evaluation

Preoperative and postoperative voice analysis was available in the charts of 19 of our patients. Routine voice analysis included registration of maximum phonation time (MPT), peak sound pressure (PSP) levels, and phonational frequency range (PFR). MPT was evaluated by asking patients to sustain the vowel / a/ as long and steadily as possible. PSP was measured with an integrating impulse sound level meter (type 2226, Brüel & Kjær, Naerum, Denmark) at a distance of 30 cm from the patient's lips. PFR was measured by determining the highest and lowest frequencies the patient could sing. The range between the highest and lowest tones sung was determined by the number of halftones sung by the patient using the equal-tempered musical scale.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. BIBLIOGRAPHY

Demographic Data

The CIS patients included 23 men and 6 women ranging in age from 46 to 75 years (mean age, 60.5 y). Twenty-five patients (86%) were heavy smokers (more than 20 cigarettes per day). Follow-up ranged from 25 to 143 months with a mean duration of 82 months.

Staging, Diagnosis, and Initial Treatment

All patients had video stroboscopy preoperatively to determine the vibratory patterns of the vocal fold mucosa and to identify regions of impaired mucosal wave.

Tumor sites, initial treatment, and follow-up data are given in Table I. All patients had glottic CIS. Transoral superficial or subligamental laser cordectomy was the initial treatment modality in all lesions, performed in 22 patients after microlaryngoscopic biopsy. In the remaining seven patients, the complete lesion was removed by superficial or subligamental laser cordectomy as excisional biopsy during the first diagnostic microlaryngoscopic intervention.

The histological examination of the surgical specimens indicated residual disease in patients 9 (anterior commissure) and 13 (left vocal cord). The residual disease of these patients was removed with one additional laser procedure.

No tracheotomy or neck dissection was performed in this series. No postoperative radiation therapy was given to any of the patients.

Postoperative Healing Process and Complications

Re-epithelization of the nonclosed surgical defects was complete within 2 to 4 weeks after transoral surgery, depending considerably on the size of the surgical defect. All patients were advised to resume their normal diet on the first postoperative day. Patient 2 had prolonged dysphagia with recurrent aspirations. Intravenous antibiotic therapy was administered (to prevent aspiration pneumonia) in combination with an intensive training for swallowing. The laryngeal function improved, allowing discharge with oral diet within 2 weeks. Patient 23 developed a scar formation of the anterior commissure after laser resection, requiring further laser microlaryngoscopic treatment.

Follow-up and Local and Regional Control

Follow-up revealed 23 patients to be alive and free of disease from 25 to 143 months after initial laser surgery. Six patients (patients 2, 4, 10, 11, 19, and 20) died of intercurrent diseases without local recurrence 26 to 137 month after surgery. Local control with initial treatment was achieved in 86% of the patients. Patients 2, 5, 8, and 14 developed local recurrences of laryngeal CIS between 13 and 74 months after initial laser resection. Three of these patients were subsequently treated with one additional CO2 laser surgery. All have since remained alive and free of disease for 22 to 123 months. Only patient 2 had multiple recurrences of CIS, requiring four transoral laser interventions. He died during a severe heart attack with cardiac infarction 41 months after the last laser surgery without evidence of local recurrence. No cases of invasive recurrence were recognized. Patients 13 and 17 were lost to our follow-up 83 and 40 months after initial therapy, respectively.

Three patients (patients 2, 11, 22) developed second primary malignancies (carcinoma of the auricle T1N0M0, carcinoma of the tongue T2N0M0, bronchogenic carcinoma T2N1M0). There were no tumor-related deaths in this series. No patient required laryngectomy or radiation therapy for salvage.

Phonatory Outcome

All 19 patients with preoperative and postoperative voice analysis had impaired vocal function as rated by the auditory perception of a patient's voice at the time of initial diagnosis. Indeed, voice impairment was the symptom that caused medical examination leading to the final diagnosis of laryngeal CIS in the vast majority of patients. The mean maximum phonation time was 13 seconds (range, 4–19 s) before surgery and 12 seconds (range, 3–21 s) after surgery. The mean phonation frequency range decreased from 12 halftones (range, 8–20 halftones) before to 10 halftones (range, 5–17 halftones) after surgery. The peak sound pressure level remained virtually unchanged. The preoperative mean value was 82 dB (range, 72–99 dB), and the postoperative mean value was 83 dB (range, 71–98 dB). These measurements indicate only minor phonatory dysfunction after transoral resection of glottic CIS and practically no phonatory change compared with the individual patient's vocal ability before surgery.

A comprehensive assessment of voice quality cannot be performed by measuring individual phonatory parameters. The standard of voice assessment remains the auditory perception of a patient's voice by a well-trained voice pathologist. Therefore the data presented in this study can only give an incomplete impression of phonatory changes secondary to the interventions discussed. However, auditory perception of voice invariably depends on the examiner's subjective impression and cannot be reliably quantified. The vocal parameters tested in this study provide information on individual phonatory qualities that can be expected to undergo significant alterations after surgery for the widening of the glottis. They have repeatedly been used to assess voice changes in patients with recurrent laryngeal nerve paralysis 8 and therefore may well be considered to provide relevant information on the potential impact of airway-restoring surgery on vocal ability.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. BIBLIOGRAPHY

The incidence of CIS was often overestimated in studies of the 1970s, where the lesions accounted for approximately 8% to 15% of all laryngeal carcinomas. 17–19 In the present series, the incidence of CIS was 4% of all glottic carcinoma (n = 596) treated in our institution in the observation period and similar to that quoted in the recent literature. 3 Re-examination of histological material frequently has revealed that 20% to 50% of original diagnoses include microinvasive lesion, characterized by infiltration of both the basement membrane and the underlining stoma. 3,20–22 These tumors are capable of metastasizing. The inclusion of these tumors, which did not fulfill the criteria of CIS, may be responsible for the overestimation of the incidence of CIS and probably are responsible for the confusion of the treatment recommendation for glottic CIS as well.

Adequate biopsy specimens are necessary to establish the diagnosis of CIS, allowing the pathologist to examine the deeper layers of the specimen to better understand the relationship between epithelium and the underlining stroma. 3,23 Therefore the lesion was removed completely by transoral CO2 laser surgery in seven cases performed as an excisional biopsy. This procedure allowed the establishment of the final diagnosis and was therapeutic at the same time.

The treatment of CIS of the larynx is not settled. Primary treatment protocols usually include radiotherapy or surgery as single agents. Radiotherapy is the preferred method of treatment for laryngeal CIS in the majority of recent reports in the literature. 10,24,25 The main advantages of radiotherapy over surgery with cold instruments are believed to be better voice preservation and a higher rate of initial local control. 9,10,26 Furthermore, Fein et al. 10 recommended a radiotherapeutic approach, arguing that long-term results of CO2 laser surgery are lacking in the current literature. Other authors have thought that primary surgery should be the treatment of choice, stressing that irradiation may promote conversion of CIS to invasive cancer and that it is easier to detect early recurrences after endolaryngeal surgery than after irradiation. Furthermore, if invasive carcinoma develops, the patient can be offered a curative course of radiotherapy. 27,28

The current major options in primary surgical therapy for CIS of the larynx include both vocal cord stripping with cold instruments and laser surgery. Treatment methods, initial failure rates, ultimate local control rates, and laryngeal preservation rates of laser surgery were reviewed in the literature and are given in Table II. All except 48 patients (data reported in eight series 20–22,29–33) were treated with radiotherapy or conventional surgery. The outcome in patients with CIS were pooled with that of microinvasive lesions in the majority of series, limiting the comparability of previous results with our data. Furthermore, laser surgical procedures performed in these patients are not uniform. Some authors preferred laser excision for CIS. 29,32 Others advocated more conservative treatment strategies, mainly laser vaporization. 33 A third group of authors used heterogeneous treatment strategies. 21,30

Table Table 2.. Results of CO2 Laser Surgery: A Review of the Literature and Current Data.
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The results reported on radiotherapy, conventional surgery, and laser surgery in the literature and our data are summarized in Table III, irrespective of different treatment strategies. The rates of initial local failure and ultimate local control after radiotherapy were similar to those reported after laser surgery and superior to those with conventional surgery. However, the fundamental advantage of laser surgery is the high laryngeal preservation rate, which is 7 times higher than the rate reported after radiotherapy and 12 times higher after conventional surgery. Fein et al. 10 supposed that better larynx preservation rates for laser surgery may be due to short follow-up in reported series. In our series, all patients had a follow-up of more than 2 years and no larynx was lost, refuting the latter supposition. Based on our material, CIS of the larynx is best handled by submucosal or subligamental CO2 laser cordectomy (Fig. 1).

Table Table 3.. Rates of Initial Failure, Ultimate Local Control, and Larynx Lost After Laser Surgery, Conventional Vocal Cord Stripping, and Radiotherapy of Patients With Carcinoma in Situ.
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Figure Fig. 1.. Submucosal laser cordectomy of the left vocal cord and subligamental laser cordectomy of the right vocal cord with preservation of the anterior commissure (performed in patient 22).

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The benefits of carbon laser surgery have been related to the precise application, minimal bleedings and tissue damage of surgical trauma, and rapid healing. 11,14,15 It has been reported to cause minimal morbidity, have good functional results, and provide a cost-effective alternative to open surgical procedures and to radiotherapy. 13 Only four patients treated in this fashion had local recurrence, only one patient required more than one additional endoscopic intervention, and only two patients in our series had temporary postoperative complications. Therefore, considering the excellent local control and laryngeal preservation rate, the CO2 laser has been the instrument of choice at the authors' institution for CIS.

In contrast to most previous publications on the treatment of laryngeal CIS, surgical excision of the glottic lesion was not always limited to the mucosal layers. In eight cases, a subligamental cordectomy was performed. This may seem to be overtreatment, since CIS is by definition confined to the mucosa and there should be no need to resect anatomical structures deeper to the mucosal layer. However, it is well known from the laryngeal literature that the mucosal wave is frequently disturbed in glottic CIS, and frequently Reinke's space is not clearly discernible under magnification of the anatomical structures with the operating microscope. Although it allows for a magnified view of the anatomical structures in the larynx, it does not replace the pathologist's microscope in the histopathology laboratory. Therefore we choose to perform a more comprehensive type of cordectomy than previously reported in the literature. Although this approach may trade voice quality for oncological soundness in some cases, we believe that long-term local control of the disease, ideally achieved with only one therapeutic intervention, may eventually be more beneficial for the patients' well-being than more cautious resections that bear a higher risk for future recurrences. In addition, the phonatory outcome analysis of our patients shows that voice impairment secondary to the surgical procedures used in this study is only minimal.

The authors have to admit that it is not always easy to determine the ideal extend of the resection for a given case. This dilemma is illustrated by the fact that four of our patients developed local recurrences during follow-up and needed further treatment. All of them had initially been treated with submucosal cordectomy. In light of the observation that none of the eight patients in our series who were managed more aggressively with subligamental cordectomy had local recurrences, we recommend from our data that more extended glottic resections than traditionally advocated for this disease may be beneficial for a subset of patients presenting with extended disease and/or impaired vibratory patterns on preoperative stroboscopy. However, further prospective clinical research work must be conducted to test this hypothesis.

CONCLUSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. BIBLIOGRAPHY

Transoral submucosal or subligamental laser cordectomy can be highly effective for the treatment of CIS of the glottic larynx if pathological evaluation of the margins is obtained. Local control rates are comparable to those reported after radiotherapy and superior to those after conventional surgery. However, with close, long-term follow-up, patients undergoing endoscopic therapy have an overall outcome superior to that in patients treated with radiotherapy before developing invasive disease. These findings support a laser surgical approach. The prognosis of the neoplasm is excellent when adequate treatment is adopted from the beginning. Superficial CO2 laser cordectomy is the method of choice in CIS of the larynx to minimize tissue trauma, local recurrence, and lost larynges.

BIBLIOGRAPHY

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. BIBLIOGRAPHY