|Year : 2014 | Volume
| Issue : 2 | Page : 104-108
Prospective study of outcomes of surgically treated larynx and hypopharyngeal cancers
BT Varghese1, S Babu1, KP Desai1, AS Bava1, P George2, EM Iype1, B Rajan3, P Sebastian1
1 Department of Surgical Oncology, Regional Cancer Centre, Trivandrum, Kerala, India
2 Department of Clinical Epidemiology, Regional Cancer Centre, Trivandrum, Kerala, India
3 Department of Clinical Oncology, National Oncology Centre, Royal Hospital, Muscat, Oman
|Date of Web Publication||7-Aug-2014|
B T Varghese
Department of Surgical Oncology, Regional Cancer Centre, Trivandrum, Kerala
Source of Support: Grant from Kerala State Council for Science technology and environment (India)., Conflict of Interest: None
Objective: To determine the morbidity and survival of surgically treated locally advanced carcinoma larynx and hypopharynx in a tertiary referral center in South India, a prospective cohort study was carried out. Materials and Methods: Patients who had undergone laryngectomy or laryngopharyngectomy from January, 2006 to January, 2011 at our institute were prospectively studied for factors affecting morbidity tumor recurrence and disease free survival (DFS). DFS was calculated for the whole group and for the larynx and hypopharynx cancer subgroups separately, using Kaplan Meir Method and the survival differences of the larynx and hypopharynx groups and between salvage and primary surgical cases were evaluated using the Cox's regression scale . Results: A total of 154 patients with ages ranging from 23 to 78 (mean 56.3 + standard deviation 9.2) were studied, which included 145 males and 9 females. Pre-operative tracheostomy and previous radiotherapy were the most significant factors contributing to post-operative morbidity. Survival difference between the larynx and hypopharynx cancers was statistically significant and the DFS was significantly affected by primary site wound infection, primary site margin and node positivity. Conclusion: The results of laryngectomy can be optimized by "proper case selection and morbidity risk assessment".
Keywords: Laryngectomy, morbidity, outcome, survival
|How to cite this article:|
Varghese B T, Babu S, Desai K P, Bava A S, George P, Iype E M, Rajan B, Sebastian P. Prospective study of outcomes of surgically treated larynx and hypopharyngeal cancers. Indian J Cancer 2014;51:104-8
|How to cite this URL:|
Varghese B T, Babu S, Desai K P, Bava A S, George P, Iype E M, Rajan B, Sebastian P. Prospective study of outcomes of surgically treated larynx and hypopharyngeal cancers. Indian J Cancer [serial online] 2014 [cited 2019 Aug 23];51:104-8. Available from: http://www.indianjcancer.com/text.asp?2014/51/2/104/138140
| » Introduction|| |
Carcinoma of the larynx accounts for approximately 2% of all cancers. Conservative surgery or radiotherapy (RT) offers equal cure rates in its early stage although RT is more popular world-wide. For intermediate and advanced staged tumors total laryngectomy with post-operative RT was the standard of care until the Veterans Administration Larynx Study in 1991 and other subsequent organ preservation trials which established the role of chemo radiation in the upfront treatment of intermediate laryngeal cancers (stage III and early IV a). Hypopharyngeal cancers although managed in the same lines, are more aggressive and liable for treatment failure and low survival. The incidence of these cancers is relatively high in India (11% against 1% world-wide, among males).  Surgical management of the larynx and hypopharyngeal malignancies have become increasingly challenging with the advent of on surgical organ preservation strategies. Failures of these protocols are often accompanied by post radiation sequela, which enhances post-surgical complications when a salvage laryngectomy/laryngopharyngectomy is undertaken. We present a 5 year prospective study of surgical management of the larynx and hypopharynx cancers at Regional Cancer Centre, Trivandrum, India, with an aim to study the survival and morbidity of the treated patients.
| » Materials and Methods|| |
Institutional review board and local ethics committee approval was obtained for a prospective study of morbidity and survival pattern of patients undergoing laryngectomy or laryngopharyngectomy at our institute during the period of January, 2006 to January, 2011 Profoma based prospective data was entered into a computerized database (Microsoft excel software) and studied for survival and factors affecting morbidity and recurrence. The site and stage distribution of the disease, type of laryngectomy, method of pharyngeal reconstruction, pathological status of primary and nodes, complications, recurrence and post laryngectomy voice rehabilitation were recorded. Morbidity factors that were analyzed included RT, previous tracheostomy, chemotherapy (CT), concomitant neck dissections, acid peptic disorders (APDs), hypertension and chronic obstructive pulmonary disease (COPD). The other morbidities recorded were chyle leak, post-operative hemorrhage and hematomas. Disease free survival (DFS) was calculated for the whole group and for the larynx and hypopharynx cancer subgroups separately, using Kaplan Meir Method and the survival differences of the larynx and hypopharynx groups and between salvage and primary surgical cases were evaluated using the Cox's regression scale. The follow-up period ranged from 1 month to 59 months with a median of 20 months.
| » Results|| |
A total of 154 patients with ages ranging from 23 to 78 (mean 56.3 + standard deviation 9.2) were studied, which included 145 males and 9 females. The site and stage distribution, the status of the patient at the time of surgery, type of laryngectomy, neck dissection and reconstruction methods used, voice rehabilitation, recurrence and complications are shown in [Table 1]a-c. Total laryngectomy was done as the primary treatment modality only when the T staging was 4a or when the histopathology precluded primary RT (e.g., spindle cell carcinoma) or when the general condition of the patient was poor to tolerate CT-RT or when there was severe laryngeal dysfunction.
Immediate post-operative wound exploration was needed in four cases of which three were for neck hematomas and one for chest hematomas. CT was the most common factor in all of them. Jugular blow out was seen in a post-CT borderline inoperable cancer of the supraglottic larynx extending to subglottis, pyriform fossa, base of tongue and post cricoid area with bilateral lymph node involvement (T4N2cM0). The surgery was undertaken after two cycles of induction CT to downstage the disease (neo-adjuvant CT). On the whole, 40 patients received CT either in a neo-adjuvant setting or as a part of CT-RT. Although the numbers were very few to draw a conclusion, CT independently or in conjunction with curative RT seems to be an important factor pre-disposing to re-explorations related to bleeding or hematomas (P = 0.001) in the current study.
Tracheostomy was more frequent among primary surgeries and Diabetes mellitus was distributed more in the salvage group because patients with advanced cancers not suitable for non-surgical organ preservation protocols frequently presented with airway obstruction and those with diabetes mellitus often preferred non-surgical management even in advanced stages.
Primary site wound edge infection was more in salvage cases (P = 0.010) and so was wound dehiscence (P = 0.024), drain site infection (P = 0.019), pus collection (P = 0.018), skin flap necrosis (P = 0.031) or transferred skin flap necrosis (0.021), donor site wound edge necrosis (0.004) dehiscence (0.005), drain site infection (0.011) and pus collection, 0.011) pharyngocutaneous leaks (PCL) (0.027) and readmissions for PCL. Besides RT other morbidity factors that were analyzed included previous tracheostomy and CT, concomitant neck dissections, APDs, hypertension and COPD. The other morbidities recorded were chyle leak, post-operative hemorrhage and hematomas.
Airway interventions were performed mostly on an emergency basis and tracheostomy was significantly correlated to the primary site wound infection (P = 0.006), donor site wound infection and dehiscence (P = 0.034 and 0.014) where pectoralis major myocutaneous (PMMC) flaps were used, drain site infections (P = 0.014) and pus formation (P = 0.014) in general, leak (P = 0.008) and minimal hemorrhage (P = 0.012) and hematoma (P = 0.015) post-operatively.
[Table 2]a shows the distribution of PCL among the different circumstances of laryngectomy and methods of neopharyngeal reconstruction. The overall PCL rate was 27%. On univariate analysis (Pearson Chi-square) PCL showed a statistically significant correlation with RT, tracheostomy and wound infection at the primary site but on multivariate analysis, by back-ward elimination method, this was seen only for wound infection [Table 2]a. There was no statistically significant correlation with diabetes, APD or Neck dissections either on univariate or on multivariate analysis. All leaks except 2 settled with conservative treatment. Method of closure and CT did not have a significant influence on leaks [Table 2]a. Out of the 2 established pharyngocutaneous fistulae, one was treated with the local hinge flap for lining and deltopectoral (DP) for cover and in the second case, lining and cover could be achieved with advancement of the adjacent skin. DFS by Kaplan-Meir method and the survival difference between primary and salvage cases by Cox's regression scale are shown in [Figure 1] and [Figure 2] and [Table 2]b. There was a statistically significant survival difference between the larynx and hypopharynx cancers [Figure 1]b although it was not so when a comparison was made between salvage and primary surgical cases, among the whole group and among larynx and hypopharynx cases [Figure 2]a and b. DFS was significantly influenced by primary site wound edge infection, primary site margin and node positivity as shown in [Table 2]c. Univariate analysis by Chi-square test showed statistically significant correlation with all the variables, but multivariate analysis by backward elimination showed node positivity alone as a significant factor.
|Figure 1: (a) Disease free survival by status of disease, (b) Disease free survival by site of disease|
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|Figure 2:(a) Disease free survival by status of the disease among laryngeal cancers, (b) Disease free survival by status of disease among hypopharyngeal cancers|
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| » Discussion|| |
Surgery as a treatment modality for cancer of the larynx and hypopharynx has been pushed to the back seat with the advent of chemo-radiation, in spite of the resurgence of interest in open and closed conservation surgical procedures in upfront management of early cancers. , The only situation where it is uniformly used as an upfront treatment modality is in T4a lesions of the larynx and hypopharynx where there is frank invasion of the outer cortex of the laryngeal cartilaginous frame work (penetration). The current evidence however also acknowledges the chances of a high failure rate of a non-surgical organ preservation protocol in intermediate stages of cancers of the hypopharynx and difficulty in salvaging these cases surgically. , This is the rationale for the resurgence of interest in induction CT for intermediate stage cancers of hypopharynx, whereby these cases are given a course of CT for two cycles and the response assessed. If there is more than 50% response, the treatment is consolidated with concurrent CT-RT or else (if response less than 50%) surgery is planned (to salvage the failing situation!). An alternative here is to go ahead with concurrent CT-RT with the caveat that an early failure of this treatment in the form of significant tumor persistence associated with immediate and intermediate chemo-radiation related toxicities and sequelaes is extremely difficult to salvage surgically without any morbidity, increased incidence of complication and occasional mortality. ,, The success rates of these salvage procedures are often commensurate with the availability of reconstructive surgical facilities in a center. When surgery is inevitable, wherever possible, a carefully executed conservation laryngectomy that preserves the voice alone (near total laryngectomy) or voice and airway (open partial laryngectomyOPL or supracricoid laryngectomySCL) is used to address cost and maintenance issues in voice rehabilitation, which is highly relevant for a low resource setting like ours. ,,
Wound related complications in general were found to be more in salvage surgeries which was also reflected in the fistula rates. Closed stapling was found to be a reliable alternative to suturing when the cancer is endolaryngeal. Stapling devices have gained popularity in neopharyngeal closures after laryngectomies over the past few decades.  Open and closed methods of closures are described in the literature. Improved operating time and lesser field contamination and chance for manual errors are the essential advantages of closed stapling in laryngecomy. Furthermore, our experience points  toward the liberal usage of vascular flaps like PMMC flap to augment deficiency of pharyngeal closure and the current study further validates this observation. All the leaks after flap closures settled without leaving behind a pharyngocutaneous fistula. Our low threshold for supplementing vascularized pedicled flaps and using staplers in suitable situations is based on our published , and unpublished experience before the current study was undertaken.
An interesting finding in the present study was the correlation between post-operative wound edge infection and DFS. The plausible explanation for this would be the associated immunodeficiency in all those patients in whom the cancer recurs. We have observed that the incidence of treatment sequlae after chemo-radiation and the therapeutic dilemma is treating them is very challenging to the surgeon. An apparently disease free patient who is on Nasogastric Tube feeds or feeding gastrostomy/jejunostomy with a tracheostomy tube for obstructed airway is a classic example of a situation where an organ preservation protocol has apparently succeeded in terms of larynx preservation and survival but not in terms of true (functional) organ preservation.  The ethics and justification of surgical intervention in the form of laryngectomy in these circumstances have not been discussed widely. ,,,
Prudence in executing a salvage surgical therapy is very crucial in the overall survival of the patients as it can adversely affect survival as indicated by some retrospective studies. ,,, On the other hand, judicious selection of the most appropriate case at the appropriate time before the tumor residue or recurrence progresses is known to offer survival advantage as indicated by our present and past experience.  To this end, we advocate a stringent follow-up policy for all patients subjected to organ preservation protocols or trials.
Pre-treatment or peri treatment tracheostomy also influences the outcomes of non-surgical organ preservation. Tracheostomy enhances the predisposition to major toxicities, such as aspiration, perichondritis and chondroradionecrosis, radiodermtitis and dysphagia. The influence however depends on the circumstances of the tracheostomy, maintenance of the inserted tracheostomy tube and the care of the surgical site. Complication related to tracheostomy (for e.g.,: Low tracheostomy, infection at the site of tracheostomy, dislodgment of tracheostomy tubes and false track formation) especially those done in emergency settings adversely affects the treatment outcome. The recommendations of the larynx preservation conservation panel  insists on comprehensive laryngopharyngeal function preservation along with survival as the primary end point and the secondary end points include duration of tracheostomy, time to laryngectomy and the time to discontinue feeding tube. The panel also encourages studies addressing outcomes and characteristics of those patients who have failed an organ preservation protocol. The current study, which is a direct continuation of a retrospective analysis completed by us in 2005  is one of its kind.
Among the subset of tracheostomized patients in the current study we noticed that maintenance of tracheostomies done before or during radiation or CT is extremely difficult especially in the presence of complications like infections and low tracheotomy (where the skin opening is at a higher level than the tracheotomy), which is frequently accompanied by tube dislodgement and false track formation. This is partly because, very often the patients are not able to buy costly (tailor made) tracheostomy tubes designed to tackle several of these tracheostomy related problems. Decannulation of tracheostomy tubes is often not feasible due to subglottic fibrosis and granulation and retracheostomy of decannulated patients are also challenging when the initial tracheostomy was complicated by a low placement of the tracheostomy tube (which is often inevitable in short necks).
An important issue in the management of larynx and hypopharynx cancers is the role of airway management and the facility available for it. Airway obstruction and its failed management as a major causative factor for impaired survival have not been documented properly in literature. Very often a survival figure for a patient is a direct effect of a successful airway intervention in the form of an emergency tracheostomy done by a surgeon in a peripheral center or by a resident in a referral center. In the current study, we have therefore documented pre-operative tracheostomy and the circumstances that lead to it to address this issue and found that most of the tracheostomies were performed on an emergency basis. These patients showed poor quality-of-life due to aggravation of laryngeal dysfunction after the procedure.
| » Conclusion|| |
Besides the potential of upfront (primary) surgery to cure locally advanced (T4) cancer of larynx and hypopharynx, a high degree of salvage can be achieved in both larynx and hypopharynx cancers with "proper case selection." On the other hand, improper case selection and execution can adversely affect the overall outcome of anorgan preservation strategy. The role of primary surgery seems to be higher in hypopharyngeal cancers and owing to its biologically aggressive behavior, hypopharyngeal cancers require close follow-up after an organ preservation protocol, to detect recurrence at the earliest and plan for an effective salvage surgery. Liberal usage of pedicled skin flaps have helped us to contain the pharyngeal fistula formation rate after total laryngectomy and linear stapling devices have been an useful adjunct in selected cases because of its efficacy and simplicity.
| » Acknowledgments|| |
We wish to thank Kerala State Council for Science Technology and Environment (KSCSTE) for the financial grant extended to the study and Ms. Rekha for secretarial assistance in the preparation of this manuscript.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]