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Year : 2017  |  Volume : 13  |  Issue : 5  |  Page : 856-861

Influence of risk factors on stomal recurrence after total laryngectomy for laryngeal carcinomas: A meta-analysis

1 Department of Otolaryngology, Changhai Hospital, The Second Military Medical University, Shanghai; Department of Otolaryngology, Jinling Hospital, Nanjing Clinical Medical College, The Second Military Medical University, Nanjing, China
2 Department of Otolaryngology, Second Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, China
3 Department of Otolaryngology, Jinling Hospital, Nanjing Clinical Medical College, The Second Military Medical University, Nanjing, China
4 Department of Otolaryngology, Changhai Hospital, The Second Military Medical University, Shanghai, China

Date of Web Publication13-Dec-2017

Correspondence Address:
Hong-Liang Zheng
Department of Otolaryngology, Changhai Hospital, The Second Military Medical University, Shanghai 200433
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_90_17

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 > Abstract 

Background: Total laryngectomy is preserved for those the most advanced larynx cancer and nonsurgical cases. However, stomal recurrence is frequently occurred and leads to high mortality. Herein, we aimed to determine the risk factors for the stomal recurrence after total laryngectomy (SRAL).
Methods: Databases such as PubMed and EMBASE were comprehensively searched using the keywords “stomal recurrence” and “total laryngectomy.” Based on the inclusion and exclusion criteria, qualified studies would be incorporated in this meta-analysis, followed by quality evaluation and data extraction. Risk ratios (RRs) were used.
Results: A total of six studies were included in the meta-analysis, and the pooled RRs showed that subglottic location increased the incidence of stomal recurrence most among the four primary locations. Expectedly, advanced tumor stage before the laryngectomy was the risk factor for stomal recurrence, while lymph node metastases showed no difference in this meta-analysis. Further, preoperative tracheostomy increased two times more risk in the stomal recurrence compared with nonpreoperative surgery.
Conclusions: In this study, we proved that subglottic location, advanced tumor stage, especially T4 stage, and preoperative tracheostomy were risk factors for SRAL for larynx cancer. However, many other potential risk factors, such as surgical margins, could not be determined for inadequate records. Hence, more prospective trials should be designed to determine the risk factors for SRAL for larynx cancer.

Keywords: Meta-analysis, risk factors, stomal recurrence, total laryngectomy

How to cite this article:
Wang ZY, Li ZQ, Ji H, Chen W, Wu KM, Zhu MH, Zheng HL. Influence of risk factors on stomal recurrence after total laryngectomy for laryngeal carcinomas: A meta-analysis. J Can Res Ther 2017;13:856-61

How to cite this URL:
Wang ZY, Li ZQ, Ji H, Chen W, Wu KM, Zhu MH, Zheng HL. Influence of risk factors on stomal recurrence after total laryngectomy for laryngeal carcinomas: A meta-analysis. J Can Res Ther [serial online] 2017 [cited 2020 Feb 23];13:856-61. Available from: http://www.cancerjournal.net/text.asp?2017/13/5/856/220487

 > Introduction Top

Total laryngectomy is the main radical treatment for very advanced laryngeal cancers and those cases failed in the primary nonsurgical treatment. However, stomal recurrence is an extremely severe complication after total laryngectomy, and its occurrence rate ranges from 5% to 25%,[1],[2] with poor prognosis and a nearly 80% mortality rate in the first 2 years,[3],[4] which considerably worsens the survival outcomes and increases hospitalization time and medical expenses. Therefore, previous researches focused on how to prevent and determine the relevant risk factors of stomal recurrence after total laryngectomy (SRAL).[2],[5],[6],[7] However, till now, there is no systematic study evaluating the incidence and risk factors of SRAL. Hence, in this study, we adopted the meta-analysis to preliminarily discuss the relevant risk factors of SRAL and help prevent this disease.

 > Methods Top

Searching strategy and study selection

A comprehensive searching on the electronic databases, PubMed and EMBASE, were conducted with the keywords, “total laryngectomy” and “stomal recurrence.” Those studies published in English and dated from January 1990 to September 2016 were included for further consideration. Furthermore, the reference lists of the qualified articles would be fully screened.

The inclusion criteria were set as the following: (1) participants undergoing total laryngectomy; (2) the biopsy-proven stomal recurrence; (3) reporting >10 cases.

Quality evaluation and data extraction

All the data were independently extracted with the help of standardized data abstraction forms. Disagreements were resolved by discussion. The information such as first author's name, year of publication, country, study design, and characteristics of participants (age, gender, and number of samples), risk ratio (RR) or odds ratio values with 95% confidence interval (CI) was extracted from each included study.


RevMan 5.3 software (Nordic Cochrane Centre, Copenhagen, Denmark) was used in this meta-analysis. The pooled RRs were calculated for the risk factors of stomal recurrence on the fixed-effect model. The Chi-square Q-test was used to evaluate the heterogeneity between trials. When I2 > 50%, heterogeneity was detected among individual study, and the random-effect model was used to reduce the errors. The significance was set at P < 0.05, except for heterogeneity.

 > Results Top

The characteristics of included studies

A total of seven articles were preliminarily included after systematically searching databases, PubMed, Cochrane, and EMBASE, with the keywords “total laryngectomy” and “stomal recurrence.” Based on the selection criteria, six studies were finally included in the further meta-analysis.[8],[9],[10],[11],[12],[13] [Figure 1] shows the searching and selection processes.
Figure 1: The diagram for searching and selection processes

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The characteristics of these enrolled studies, such as year of publication, study designation, and characteristics of participants, were summarized in [Table 1].
Table 1: The characteristics of included studies

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The impact of primary locations on stomal recurrence

The pooled RR for stomal recurrence was 0.48 [95% CI 0.31–0.73, P = 0.0006, [Figure 2]a when comparing supraglottic with glottic, while RR was 0.19 [95% CI 0.11–0.33, P < 0.00001, [Figure 2]c with slight heterogeneity, indicating that glottic was a risk factor for stomal recurrence when compared with supraglottic. However, glottic was better than subglottic [RR = 0.24, 95% CI 0.15–0.37, P < 0.00001, [Figure 2]b. On the contrary, transglottic was even worse than glottic and supraglottic [Figure 2]d and [Figure 2]e and comparable with subglottic [Figure 2]f, suggesting that both subglottic and transglottic were risk factors for stomal recurrence after laryngectomy.
Figure 2: The pooled risk ratios of stomal recurrence comparing between two primary locations. (a) Supraglottic versus glottic; (b) glottic versus subglottic; (c) supraglottic versus subglottic; (d) transglottic versus glottic; (e) transglottic versus supraglottic; (f) transglottic versus subglottic

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The tumor stage and invasion status as risk factors for stomal recurrence

The pooled RR between moderate (T1 + T2) and advanced stage (T3 + T4) was 0.34 [95%CI 0.16–0.71, P = 0.004, [Figure 3]a with slightly heterogeneity. Further comparing between T3 and T4 stage showed that stomal recurrence less occurred in T3 stage [RR = 0.55, 95% CI 0.39–0.77, P = 0.0006, [Figure 3]b.
Figure 3: The pooled risk ratios of tumor stage before surgery. (a) Early stage (T1 + T2) versus advanced stage (T3 + T4); (b) T3 versus T4

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Only three studies recorded stomal recurrence in the context of lymph node metastases, in which it showed no difference whether there was lymph node invasion [RR = 1.08, 95% CI 0.71–1.65, P = 0.71, [Figure 4] with heterogeneity (I2 = 75%) that still existed under the random-effect model (data not shown).
Figure 4: The pooled risk ratios of lymph node metastasis

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The influence of preoperative tracheostomy on stomal recurrence

The pooled RR was 2.31 [95% CI 1.65–3.22, P < 0.00001, [Figure 5] between preoperative and nonpreoperative tracheostomy, and slight heterogeneity was detected. It indicated that preoperative tracheostomy increased 2 times more incidence of stomal recurrence than nonpreoperative surgery.
Figure 5: The pooled risk ratios of preceding tracheotomy

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 > Discussion Top

SRAL is defined as the diffusive infiltration of neoplastic tissue at the junction of the amputated trachea and skin,[14] which involves the skin around the anastomosis, soft tissues adjacent to the tracheal stoma, or both.[2],[15] Sisson et al.[16] classified SRAL into the following four types according to the recurrent location: (i) the recurrent lesion is discretely located at the superior of the stoma without esophagus involvement; (ii) the recurrent lesion is located at the superior aspect of the stoma and involved with esophageal; (iii) the recurrent lesion is located at the inferior part of the stoma, directly extending into the mediastinum; and (iv) the recurrent lesion is located at the inferior part of both sides of the stoma, usually under the bilateral clavicles. Previous and current data from multi-institutional researches indicated that surgical intervention involving mediastinal resection achieved only 45% survival rate in the first 2 years for patients with Types I and II, while the survival rate for Types III and IV patients was only 9% in 2 years.[17],[18] Therefore, prevention and defining the risk factors of SRAL are indeed urgent.

It has been reported that risk factors of SRTL include subglottic extension, advanced tumor stage, lymph node metastasis, and preoperative tracheotomy.[10],[12],[14] However, the conclusions are still under controversy. To this end, we performed this meta-analysis to determine to which extent each risk factor could influence the incidence of stomal recurrence.

Subglottic and transglottic invasion

Subglottic and transglottic tumors are reported more likely to diffuse and infiltrate directly into the thyroid adjacent to the trachea and soft tissues around the larynx through the cricothyroid membrane or metastatic lymph nodes,[19] which was consistent with our result in this meta-analysis. Furthermore, subglottic and transglottic extension showed similar incidence of stomal occurrence. One explanation for this result was that the cricoid cartilage area in subglottic extension is abundant with blood supply,[3] making this area easily invaded by laryngeal tumors. Besides, subglottic tumor is filled with adipose, resilient, and loose tissues as well as collagen fibers, which makes it difficult to recognize adequately before operation and perform resection completely, leading to high frequent occurrence of stomal recurrence.

Advanced tumor stage

The preoperative tumor stage is commonly believed to affect stomal recurrence, which usually affects patients with advanced tumors.[20] A T4 lesion is one of the significant risk factors of stomal recurrence,[8] although some studies demonstrated that stomal recurrence is not related to the primary tumor stage.[21],[22] Our results indicate that the risk of stomal recurrence is higher in locally advanced tumors (T3 and T4) than in early tumors (T1 and T2), whereas the risk of stomal recurrence is higher for T4 patients than for T3 patients, which was consistent with the previous study that primary location and T-stage were significant independent risk factors for SRTL.[13]

Lymph node metastasis

Pre- and para-tracheal lymph node metastases are usually known as an adverse prognostic factor for stomal recurrence in patients with laryngeal carcinomas undergoing laryngectomy,[10],[23],[24] attributed to the incomplete paratracheal dissection during laryngectomy. However, in this study, we found no difference in the incidence of stomal recurrence with and without lymph node metastases. One plausible explanation for this inconsistency is that paratracheal lymphatic metastasis is not an independent risk factor for metastasis and was more closely correlated with primary tumor sites. It has been demonstrated that there were no lymph node metastases in supraglottic carcinoma while approximately 15% metastases were detected in other primary sites.[9]

Considering the relationship between stomal recurrence and cervical metastasis, other research showed that the risk of stomal recurrence is higher for patients with cervical lymphatic metastasis than for those without cervical lymphatic metastasis.[25] Nevertheless, the enrolled studies in this meta-analysis were unable to systematically evaluate the impact of cervical lymphatic metastasis on tracheal stomal recurrence.

Preceding tracheotomy (at least 48 h before total laryngectomy)

It is well known that preoperative tracheotomy, which is carried out at least 48 h before total laryngectomy, is the major risk factor of stomal recurrence.[26] They proposed that the mechanism of stomal recurrence is the implantation of cancer cells in stomal tissues.[27] However, the concept of cancer cell implantation becomes impossible because of the adequate resection margin in laryngectomy. The most reasonable explanation implied that patients with the very advanced tumors usually need preoperative tracheotomy for invisible paratracheal lymphatic metastasis, which accounts for the increased risk of stomal recurrence. Rockley et al.[23] proposed an alternative mechanism indicating that the probability of cervical lymphatic metastasis and stomal recurrence is higher for patients receiving preoperative tracheotomy than for those who did not. In addition, inflammation and fibrosis of tissues around the anastomosis caused by preoperative tracheotomy make the excision of paratracheal lymph nodes difficult.[12]

However, other studies believed that salvage tracheotomy is not a factor significantly influencing prognosis. Some evidence proved that other mechanisms are more important, such as diffusion of cancer cells through pretracheal tissues or thyroid, existence of Delphian lymph nodules, and paratracheal lymphatic metastasis. Mantravadi et al.[27] proved no difference in stomal recurrence regardless of whether emergency tracheotomy was performed. Rubin et al.[28] discovered that although salvage preoperative tracheotomy as an independent variable did not increase the incidence of stomal recurrence, subglottic extension was the most important single variable affecting stomal recurrence. Nevertheless, the result of our analysis supports that preoperative tracheotomy (at least 48 h before total laryngectomy) is one of the risk factors for tracheal SRAL.

Other risk factors

Some studies showed that the risk of stomal recurrence for patients with a positive surgical margin increased.[12],[29] Petrovic and Djordjevic pointed out that postoperative radiotherapy might reduce the risk of local reoccurrence.[10] Based on their study, regardless whether patients presented glottis or subglottic extension, exhibited local tumor invasion, and performed preoperative tracheotomy, the probability of stomal recurrence was lower for patients receiving postoperative radiotherapy than for those who did not, for cancer cells might diffuse and infiltrate through pretracheal tissues and the thyroid into Delphian lymph nodules, leading to lymph node metastases. Therefore, taking care of thyroid, pretracheal tissues, and esophageal grooves during surgery is important for the prevention of stomal recurrence.

This paper preliminarily discusses partial influencing factors of SRAL to provide a reference for the prevention of this disease. However, some shortcomings of this meta-analysis exist. For instance, publication and selection biases exist in nonspecific clinical research, which may affect the conclusions of this meta-analysis. Besides, since the included studies were retrospective clinical trials, many variables were not under full consideration. Hence, more prospective trials should be designed to determine the risk factors for SRAL for larynx cancer.

 > Conclusions Top

Subglottic and transglottic extension, advanced tumor stage, especially T4 stage, and preoperative tracheostomy were independent risk factors for SRAL for larynx cancer. Lymph node metastasis as a correlated factor contributed to increase incidence by mean of primary tumor location and should also be paid attention to. Many other potential risk factors, such as surgical margins, could not be determined for inadequate records. Afterward, more multi-institutional prospective trials should be conducted to shed new light on the determination of risk factors and prevention of SRAL.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

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