Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature.

It was not until 1873 that an attempt was made to treat cancer of the larynx by surgical means. In that year, Billroth performed the first laryngectomy for cancer. However, radiation treatment predominated until the late 1930s and early 1940s, due to the hazard of infection, the risk of anesthesia complications, blood and fluid loss during the procedure, and reconstructive problems. The introduction of sulfa in 1935 and PCN in 1938, the use of ET tube anesthesia, and the introduction of numerous dermatomes for skin grafting, which were developed in 1939, all contributed to a more aggressive approach to the surgical treatment of laryngeal cancer. However, as laryngectomies became more prevalent, the problem of stomal recurrence began to appear.

Stomal recurrence has been defined as a diffuse infiltrate of neoplastic tissue at the junction of the amputated trachea and skin. This is a dreaded complication in the treatment of laryngeal carcinoma. Once it has been diagnosed, the outlook for the patient is extremely poor - death occurs within 2 years, usually secondary to progressive tracheostomal obstruction or hemorrhage caused by erosion of the major vessels. Ninety-three percent of patients with stomal recurrence are male, with an age range of 46 - 79, with a mean of 61.7 years of age. In 17 series of patients reported in the literature, the range of stomal recurrence was 2.5% to 15% for patients with squamous cell carcinoma of the larynx. In their comprehensive review of 20 references encompassing 4,281 laryngectomies, Esteban and co-workers calculated the overall incidence of stomal recurrence to be 6%. Any recurrence at the tracheal stoma usually occurs within the first year after laryngectomy. In fact, 98% of patients who experience stomal recurrence do so within 2 years of initial treatment. Despite the adverse prognostic implications of a peristomal recurrence, it has only been since 1962 that a concerted effort has been made to define the pathogenesis of this complication. But the precise pathogenesis is still unknown.

Since the prognosis of a patient who develops a stomal recurrence is dismal, attention should therefore focus on prevention and identification of the risk factors that may predispose the patient to a stomal recurrence. After reviewing the literature, it is evident that the small number of occurrences of stomal recurrence makes compiling a statistically significant study difficult. It seems that for each study that tries to prove a certain theory, there is another that discounts it. The recurring debates that exist, however, involve whether local implantation of the neoplasm plays a role, if the timing of a tracheotomy matters, the role of the involvement of paratracheal nodes and the location and size of the primary tumor.

In order to predict prognosis of stomal recurrences, Sisson et al. in 1976 described a classification system for peristomal recurrences. Type I is localized and usually presents as a discrete nodule in the superior one-half of the stoma without esophageal involvement. The prognosis is very good if detected early. Type II tumors involve the superior one-half of the stoma with esophageal involvement. Prognosis for Type II is fair to good depending on the amount of esophageal involvement. Type III originates in the inferior one-half of the stoma and usually has direct extension into the mediastinum. Type IV indicates there is an extension laterally and often under either of the clavicles. With either Type III or Type IV, the prognosis for short-term control is dismal.

Probably the most controversial issue regarding peristomal recurrences revolves around whether or not an emergent tracheostomy performed before a laryngectomy increases the incidence of recurrence. Some of the earlier literature reports stomal recurrence to occur about 10% - 50% more frequently when proceeded by emergent tracheotomy, citing cancer seeding into the trachea and peristomal soft tissues as the pathophysiology. The first paper written discussing this subject was Keim and coworkers in 1965, who analyzed the records of 116 laryngectomy patients. Of the 22 patients who underwent a tracheotomy some time before laryngectomy, 9 patients or 41% developed a peristomal recurrence, while of the 65 patients who did not have a prior tracheostomy, 4 patients or 6.1 % developed a peristomal recurrence. From these figures, Keim concluded that doing a tracheostomy, especially before operation, carries a high risk of peristomal recurrence.

Following this theory, two recent studies (Dr. Griebie and coworkers in 1987 and Dr. Wickham and coworkers in 1990) studied the prospect of performing an emergent laryngectomy to prevent the complication of a peristomal recurrence.

They relieved the airway obstruction either by ET or by a high tracheostomy under local, after which frozen section biopsies were taken. If the results of the frozen section confirmed SCCA, then a TL and primary excision of the initial tracheostomy site in continuity were performed, with en block radical neck dissection if indicated by the presence of palpable lymph nodes. If the frozen section report was equivocal, further biopsies were taken and the patient returned to the ward while permanent sections were assessed. In Dr. Griebie's study, 1 out of 16 patients who underwent an emergent laryngectomy developed a peristomal recurrence. This percentage is not statistically significant when compared to the reported incidence of peristomal recurrences in general. In the smaller study performed by Dr. Wickham, none of their 13 patients developed a peristomal recurrence. The disadvantages of this technique, however, are many. Frozen section analysis is not the ideal basis for planning radical cancer surgery and the time scale does not permit a thorough evaluation of possible metastases or the patient's underlying medical problems. In addition, the preoperative nutritional and psychiatric support of the patient is inevitably compromised. There is also the fact that not all studies support the conclusion that an emergent tracheostomy is a risk factor for stomal recurrence. For instance, a more recent study by Rubin and coworkers, failed to show prior tracheotomy to be an independent risk factor. In the study of 444 laryngectomy patients, they found no difference in stomal recurrence rate among the laryngeal cancers that required emergent tracheotomy. Of those undergoing an emergent tracheostomy, 30.7% had peristomal recurrences, while 24.2% of those without a previous tracheostomy had a recurrence. They proposed that any difference reported in the literature probably reflects the location of the lesion and relative tumor burden rather than signifying a pathogenic relationship between timing of tracheotomy and recurrent disease at the stoma: patients with initial symptoms of airway obstruction that require emergency tracheal management have more extensive disease than those patients whose airways are uncompromised.

As an alternative means of controlling the airway, with the avoidance of a preoperative tracheotomy, Davis and Shapshay reported on the use of the carbon dioxide laser to endoscopically excise an obstructive laryngeal tumor prior to definitive treatment. In their small study, their initial results were favorable, and this would appear to be another treatment modality that might avoid the debate concerning emergent tracheotomies altogether. However, in their cases they initially secured the airway by means of ET, a procedure that is not without risk in some patients with large obstructing lesions. In addition, as previously stated, the role of an emergent tracheostomy as a risk factor for peristomal recurrence is not definitive.

Another risk factor that has been proposed involves the particular role of endotracheal intubation as a means of tumor implantation. In 1953, Ormerod and co workers thought that a major cause of failure of laryngectomy to control disease was the use of endotracheal anesthesia. He postulated that the tube transferred malignant cells from the laryngeal lesion to the trachea where implantation occurred. In a more recent study, Dr. Dejong compared 51 patients having a tracheostomy under local anesthetia at the start of a laryngectomy with 63 patients having oral ET and laryngectomy. One patient in each group developed a stomal recurrence. There was no significant difference between the studied groups. Numerous other authors have also supported the results of this study. However, tumor implantation cannot be discounted as a mechanism. There are reported cases in which stomal recurrence has developed in a tracheotomy incision after performing cancer surgery on other distant sites in the head and neck. In addition to local implantation, one cannot discount the possibility of a primary SCCA coincidentally occurring at the tracheostomal site, although this scenario is actually quite rare.

Other major predictors of stomal recurrence appear to be related to the size and location of the primary tumor. Patients with T4 lesions were significantly more likely to have stomal recurrence than were patients with smaller lesions. In Rubin's study, 8.6 % of all T4 primary lesions developed a stomal recurrence, while 0% of T1 tumors developed a recurrence, 2% of T2 tumors and 2.9% of T3 tumors developed a recurrence. In Yotakis's study, patients with larger primary tumors were more likely to develop a stomal recurrence as well. Stomal recurrence was seen in 2.3% of patients with T2 tumors, in 4.1% with T3 tumors and in 15.3% in T4 tumors. Statistical significance was shown only for T4 tumors. The reasoning behind these results is thought to be that T4 lesions have a longer time to metastasize, and they also have a greater chance of reaching the subglottic area. Then, metastasis to the PT nodes is common and this mechanism is thought to contribute highly to peristomal recurrences.

Concerning the location of the tumor, most patients with stomal recurrence have lesions involving the subglottis. Because of the proximity of a subglottic tumor to the tracheostoma, it seems logical to consider the presence of a tumor in the subglottis to be an important risk factor in stomal recurrence. A distinction is frequently made between tumors that arise primarily in the subglottic larynx and those that arise in the glottis or supraglottis and develop secondary subglottic extension. In summarizing the data, a number of trends emerge. Secondary subglottic cancer is more common than are primary subglottic tumors - 18% vs. 3.2%. Initial clinical symptoms are also different. Patients with tumors confined to the subglottis are more likely to experience symptoms of airway obstruction, such as dyspnea and stridor - 62.5% vs. 3.7%. This can be explained by the fact that unlike supraglottic or glottic tumors, subglottic tumors are prone to extensive circumferential growth and cartilage invasion. In contrast, hoarseness is the most common presenting complaint in patients with secondary subglottic cancer - 91% vs. 34%. In addition, patients tend to seek treatment for primary subglottic lesions at a more advanced stage than they do for secondary tumors since symptoms develop much later in primary subglottic tumors. However, once any lesion reaches the subglottis, it may begin to act like a subglottic primary. In Dr. Rubin's study, the presence of tumor in the subglottis - either transglottic tumors or primary subglottic tumors - was the single most important risk factor in stomal recurrence. Patients with subglottic tumors have a stomal recurrence rate of 14%, which is significantly higher than the average number for all laryngeal cancer locations, with the rate at the epiglottis being 0.6%, the aryepiglottic fold being 1.3%, and the glottis being 0.8%. In their study, they also determined that clinically apparent neck disease had no seeming impact on subsequent stomal recurrences.

The reason for the inclination of subglottic lesions to cause peristomal recurrences seems to be tied intricately to the role of the involvement of the paratracheal lymphatics. Welsh, who used injection of radioactive tracers to define laryngeal lymphatic drainage, helped elucidate this subject. He showed that supraglottic injections drained primarily to the ipsilateral upper and midjugular lymph nodes as well as a small amount of uptake in the paratracheal lymph nodes and the contralateral side of the neck. Radioactive tracer was also demonstrated in the ipsilateral thyroid lobe. EM of the lymphatics of the glottis reveals a high density at the arytenoid with progressively decreasing density toward the anterior commissure. The lymphatics were the sparest on the anterior true vocal cord where most cancer of the glottis occurs. Once the cancer reaches the arytenoids, the tumor is able to follow the lymphatics of the supraglottis. Injections into the subglottic larynx showed remarkable proclivity of paratracheal lymph nodes as well as the ipsilateral thyroid, supporting the removal of the lobe in continuity with paratracheal node dissection. Welsh discovered that 96% of the tracer could be detected initially in the paratracheal nodes. Harris and Butler also discovered clinically undetectable paratracheal lymph node metastasis present in 50% of all larynges with subglottic tumors examined by serial section. In addition, Weber et al also noted that squamous cell carcinomas arising in the subglottic larynx conferred a higher risk for metastasis to paratracheal lymph nodes. In fact, in his study, he found 15 of 29 patients or 52% of the patients had paratracheal node metastasis in the absence of cervical metastasis. Harrison et al reported a 65% incidence of paratracheal node involvement with all subglottic tumors. From this study, Harrison concluded that a more extensive resection was necessary for subglottic cancer. Using a technique that included removal of the upper part of the manubrium to allow clearance of the paratracheal nodes and the creation of a low tracheostomy, he found that no stomal recurrence developed in 12 patients who were followed for at least 2 years.

Efforts to prevent stomal recurrence focus on two interventions. First is the use of postoperative radiation of the stoma. Weber and colleagues studied 141 patients who underwent total laryngectomy, hemi- or total thyroidectomy and paratracheal LN dissection for carcinoma of the larynx, hypopharynx, or cervical esophagus. Stomal recurrence developed in 6 of 76 patients who did not receive stomal radiation postoperatively and in 0 of 65 of those who did. Tong et al reviewed the records of 26 patients given postoperative elective irradiation to the cervical region. The majority of the patients had clinically advanced lesions - 18 had stage III or IV, 7 had stage II, and 1 had stage I disease. Twenty-five of the patients had a tracheotomy at the time of resection, and one as an emergency. All patients had a high risk for stomal recurrence with their definition being: 1) extensive primary lesion, 2) subglottic extension, 3) inadequate margins , 4) paratracheal lymph node involvement, and 5) perineural or venous invasion by the tumor. Postoperative irradiation was begun as soon as the surgical wound healed. The stoma was included in the high dose volume in 22 of 26 of the patients. Dose ranged from 2600 rads to 6400 rads, with the mean dose of 5300 rads. None of the 22 patients who received peristomal radiation developed a recurrence by the time of death or at the end of the study. Of the 4 that did not receive stomal radiation, 2 had a recurrence.

Another intervention used to decrease stomal recurrence is the addition of paratracheal lymph node dissection in all laryngeal cancers with subglottic extension. Hosal and co-workers reported a decline in stomal recurrence among 488 laryngectomy patients, from 11.5% in cases before 1968 to 2.7% in subsequent cases with the routine addition of pretracheal and paratracheal lymph node dissection in both primary and secondary subglottic cancer. Sisson and coworkers in 1976 described from their experience with 100 total laryngectomies, none of which had stomal recurrence. They attribute their success to their management of subglottic disease. When a neoplasm is inferior to the cricoid and deeply invasive into the tracheal mucosa, they routinely extend the dissection into the superior mediastinum to afford an increased tracheal margin as well as to include the paratracheal nodes in the surgical block.

The development of stomal recurrence following total laryngectomy is a devastating scenario with an extremely poor prognosis. Irrespective of the etiology of the stomal recurrence, it invariably consists of diffuse infiltration of tumor into the soft tissues of the neck and mediastinum, thereby making control of the disease difficult. The management of stomal recurrence is primarily surgical. Radiation treatment has been reported to provide palliation but is ineffective when used as a single agent. Furthermore, many patients have already had a full course of radiation to control their primary cancer and are not able to receive further therapeutic doses. Combinations of radiation and chemotherapy have been used with encouraging early results in small groups of patients, and further study is needed to show if an improved survival can be consistently achieved.

Watson first described the surgical technique for removal of the affected tracheal remnant and surrounding tissue and subsequent repositioning of the tracheal stump in 1942. Sisson, however, was the first to describe a more elaborate and extensive resection and, over the years, further refined this technique with some improvement in prognosis.

Surgical treatment includes extensive removal of the tracheostoma and the surrounding skin, mediastinal dissection with removal of the manubrium and the heads of the clavicles, and resection of involved pharyngoesophageal segments with reconstruction and obliteration of dead space using various flaps. Perioperative mortality approaches 15% and is mostly due to mediastinitis and rupture of the great vessels. Overall, the incidence of these complications depend on the extent of the surgery which, in turn, depends on the extent of the disease.

Gluckman and co-workers reported the results of 41 mediastinal dissections for stomal recurrence of all the types classified by Sisson. Overall survival was a dismal 16%. Survival varied depending on the different classifications of stomal recurrence. Surgery for early disease (type I or II) resulted in a 45% 2-year survival with a relatively low morbidity and mortality. Even in those patients who failed to survive 2 years, the palliation was excellent. In the more advanced cases, type 3 or 4, surgery not only failed to offer an acceptable survival, but the perioperative morbidity was also extremely high. The 2-year survival in this subgroup was only 9%. In an analysis of the morbidity associated with the operation, Gluckman's study revealed an average hospital stay of 30 days (varying from 10 to 70 days) with 35 of 41 patients being able to return home after surgery. Of these, 17 were able to eat a regular diet, 6 a soft diet, and 11 were fed via gastrostomy tube. In Gluckman's series, the patients who were not operated on, the average survival was 6.3 months with an extremely poor quality of life.

Due to the poor prognosis of those with peristomal recurrences, the question of which patients should be offered the surgery arises. Before any major surgical procedure is undertaken, a careful medical evaluation should be performed to determine whether the patient can withstand the procedure. The patient and the family must be carefully counseled so they understand the gravity of the situation and have realistic expectations. A metastatic work up is also necessary. The next problem is to determine the extent of the stomal recurrence. CT scan of the chest and neck, barium swallow and evaluation under anesthesia are needed. Particular attention should be paid to the extent of the tracheal involvement and whether there is overt involvement of the esophagus or pharyngeal remnant. MRI has been proven useful in assessing prevertebral musculature involvement. If carotid resection is contemplated, angiography is needed to determine cerebral crossover flow. Overt mediastinal involvement, extensive tracheal involvement precluding the possibility of bringing the residual stump to the skin or tracheal reconstruction, prevertebral musculature and c-spine involvement, massive mediastinal nodal enlargement suggesting metastasis, and great vessel involvement are considered contraindications to surgery. If it can be demonstrated that the patient has type 4 disease, the data shows that there is little point of recommending surgery. Even those with type 3 disease should be viewed with some anxiety. Unfortunately, in spite of comprehensive preoperative evaluation, the full extent of the disease may only become apparent intraoperatively and therefore, the initial part of the surgery should be regarded as exploratory. First, the carotid sheaths need to be inspected, then the prevertebral musculature, and finally the superior mediastinum before actually deciding to expose the mediastinum and complete resection of the pharynx, esophagus, and trachea.

So the next question that begs answering is, is there any viable alternative to surgical salvage? For practical purposes, the answer has always been a resounding no. There has never been satisfactory evidence that radiation alone could control disease. This is compounded by the fact that most patients have previously undergone a full course radiation as part of the treatment for the original laryngeal cancer. Concerning radiation treatment alone for stomal recurrence, Tong et al treated 7 patients with recurrence. Partial or complete regression of the recurrence was noted in all patients, but 6 died 6 to 44 months following treatment. Four of these died with persistent local disease, and 2 had local control but died with pulmonary metastasis. One patient is still living but now has recurrence in an upper cervical node. Thus, despite advances in radical surgery and radiation treatment, the prognosis for stomal recurrence remains poor.

Recently, however, Snow et al reported promising results using a combination of radiation and chemotherapeutic regimen of vincristin, bleomycin, and methotrexate. In their study, they did not use Sisson's classification, but noted the location of the recurrence: 3 on the same side as the primary tumor and 3 on the contralateral. The tumor was only located at the superior aspect of the stoma in the remaining two patients. Esophageal or mediastinal involvement was not documented. In 5 of 8 patients, complete local remission was achieved with the patients surviving for 8 months, 14 months, 2.5 years, 3 years and 7 years. Two of the three of the patients that died had good local control of the disease but died of pulmonary metastasis. A problem that they encountered with this therapy is that acute epithelial reactions are more intense with combined chemo/XRT than with radiotherapy alone. Results suggest that this type of treatment must be applied as an inpatient procedure with close patient supervision. However, the problem of enhanced acute mucosal and skin reactions encountered at the end of each treatment volume did not lead to any long term damage to normal tissues in the treatment areas. Further studies are needed to validate the encouraging numbers concerning the use of chemo/XRT for peristomal recurrences.

In conclusion, until more information becomes available, surgery remains the only potentially curative therapeutic option. The data suggests that early lesions should and can be treated successfully with surgery with minimal morbidity.
Advanced lesions should be treated with more caution. Surgery for type 4 recurrence has an unacceptably high perioperative morbidity with an appalling prognosis and, therefore, should be treated symptomatically. Type 3 tumors can, under the most ideal circumstances, be treated surgically, but with realistic expectations. Unfortunately, the answer to how best treat an individual patient is obviously far more complex, and ultimately lies in a thorough understanding and appreciation of not only the disease process itself, but also the unfortunate patient who is affected by this devastating disease.

Case Presentation

J.N. is a 61-year-old white male status post XRT for a T2N0 squamous cell cancer of the right true vocal cord. He received 6800 cGy radiation to his primary site in July of 1997. In follow up, he complained of worsening hoarseness and was found to have a recurrent right true vocal cord lesion. The patient was taken to the operating room on 2/12/98 for a biopsy of his right vocal cord. The entire right vocal cord was irregular and friable. Final pathology diagnoses of moderately differentiated SCCa with focal keratinization was determined. The patient was thus taken to the operating room on 3/11/98 where a tracheostomy and a wide field total laryngectomy was performed. All lymph nodes were negative for malignancy. Pathology reports revealed a moderately to poorly differentiated squamous cell carcinoma of the right glottis with a 3 mm subglottic extension. The patient did well postoperatively, and was followed regularly in the ENT clinic.

In September of this year, the patient returned for his routine one month follow-up, and at that time, a small 1 cm pearly-appearing, raised lesion was noticed at the inferior border of his tracheal stoma. Biopsy of this lesion revealed well differentiated squamous cell carcinoma. CAT scan of the neck and chest, as well as an exam under anesthesia were both negative. The patient was taken to the operating room 2 months ago, and a margin above the inferior aspect of the stoma, 2 to 3 centimeters in size from the 1 o'clock position to the 10 o'clock position was excised above the stoma and carried down to the manubrium. Dissection was carried out down to the fascia layer, inserting on the medial aspect of the manubrium and sternum. This area was excised in its entirety including the first ring of the tracheal cartilage. There was no evident tumor. Frozen section was obtained, without evident tumor at the margins of resection. The wound was then closed using a multi-rotational flap. Post operatively, the patient has done well and remains disease free.

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