Download Paratracheal lymph node dissection in cancer of the larynx

CLINICAL REVIEW
David W. Eisele, MD,
PARATRACHEAL LYMPH NODE DISSECTION IN CANCER
OF THE LARYNX, HYPOPHARYNX, AND CERVICAL
ESOPHAGUS: THE NEED FOR GUIDELINES
Remco de Bree, MD,1 C. René Leemans, MD, PhD,1 Carl E. Silver, MD,2
K. Thomas Robbins, MD, FRCSC,3 Juan P. Rodrigo, MD, PhD,4,5
Alessandra Rinaldo, MD, FRCSEd ad hominem, FRCS (Eng, Ir) ad eundem, FRCSGlasg,6
Robert P. Takes, MD, PhD,7 Ashok R. Shaha, MD,8 Jesus E. Medina, MD,9 Carlos Suárez, MD, PhD,4,5
Alfio Ferlito, MD, DLO, DPath, FRCSEd ad hominem, FRCS (Eng, Glasg, Ir) ad eundem,
FDSRCS ad eundem, FHKCORL, FRCPath, FASCP, IFCAP6
1
Department of Otolaryngology–Head and Neck Surgery, VU University Medical Center, Amsterdam,
The Netherlands
2
Departments of Surgery and Otolaryngology–Head and Neck Surgery, Albert Einstein College of Medicine,
Montefiore Medical Center, Bronx, New York
3
Division of Otolaryngology–Head and Neck Surgery, Southern Illinois University School of Medicine,
Springfield, Illinois
4
Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain
5
Instituto Universitario de Oncologı́a del Principado de Asturias, Oviedo, Spain
6
Department of Surgical Sciences, ENT Clinic, University of Udine, Azienda Ospedaliero-Universitaria,
Piazzale S. Maria della Misericordia, Udine, Italy. E-mail: [email protected]
7
Department of Otolaryngology–Head and Neck Surgery, Radboud University Nijmegen Medical Centre,
Nijmegen, The Netherlands
8
Head and Neck Service, Memorial Sloan–Kettering Cancer Center, New York, New York
9
Department of Otorhinolaryngology, The University of Oklahoma Health Sciences Center, Oklahoma City,
Oklahoma
Accepted 31 March 2010
Published online 22 July 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/hed.21472
Abstract:
In laryngeal, hypopharyngeal, and cervical
esophageal carcinomas, the paratracheal lymph nodes (PTLN)
may be at risk for lymph node metastasis. The presence of
PTLN metastasis is an important prognostic factor for the development of mediastinal and distant metastases, stomal recurrence, and disease-free and overall survival. Studies on PTLN
metastasis are scarce. In most studies, PTLN dissection has
not been routinely performed, and selection criteria for PTLN
dissection are usually not well defined. Therefore, in most
reported studies, selection bias is present and results are difficult to compare. The reported prevalence of PTLN metastases
varies according to the site and stage of the primary tumor:
subglottic cancer, transglottic cancer, and glottic cancer with
subglottic extension have a higher risk of PTLN metastases.
Diagnostic imaging is not sufficiently reliable to detect occult
PTLN metastases and avoid unnecessary PTLN dissections.
PTLN dissection is associated with limited morbidity, but damage to major vessels may occur, and because of exposure of
these vessels PTLN may increase the morbidity of fistulae that
can occur after total laryngectomy. The dissection may pro-
Correspondence to: A. Ferlito
This article was written by Members of the International Head and Neck
Scientific Group (www.IHNSG.com).
C 2010 Wiley Periodicals, Inc.
V
912
Paratracheal Lymph Node Dissection
duce hypocalcemia, if performed bilaterally. Nevertheless, the
limited morbidity and high rate of metastasis in specific laryngeal, hypopharyngeal, and cervical esophageal carcinomas
argue in favor of routine elective PTLN treatment for these
tumors. Large prospective studies are needed to identify the
patients at risk with primary tumors in more detail. Moreover,
improved diagnostic imaging is needed to detect (occult)
PTLN metastases more reliably. Based on future studies, clinical guidelines have to be developed to avoid undertreatment
C 2010 Wiley Periodicals, Inc. Head
V
and overtreatment.
Neck 33: 912–916, 2011
Keywords: paratracheal lymph nodes; dissection; laryngeal
carcinoma; hypopharyngeal carcinoma; prevalence; diagnostic
imaging; morbidity
Head and neck cancers have a proclivity to metastasize to the lymph nodes in the neck rather than
spread hematogeneously. The prevalence of lymph
node involvement depends mainly on the site and size
of the primary tumor. The distribution of lymphatic
metastases is mainly explicable in anatomic terms
and depends on the site of the primary tumor. In
laryngeal, hypopharyngeal, and cervical esophageal
HEAD & NECK—DOI 10.1002/hed
June 2011
cancers, the paratracheal lymph nodes (PTLNs) may
be at risk for lymph node metastases. These lymph
nodes are not usually included in radical, modified
radical, or selective dissection of the lateral neck
(levels I–V).
The PTLNs are part of the central compartment,
also referred to as the anterior compartment of the
neck or cervical lymph node level VI. As recently discussed by Medina et al,1 the anatomic extension of
these PTLNs is not well defined. Generally, the lateral border is defined as the medial edge of the common carotid artery, the medial border the trachea,
and the cranial border the cricoid. The least welldefined border is the suprasternal notch, which is
considered to be the caudal border. However, the anatomic conformation of the thoracic inlet in different
patients varies.2 The PTLN and the superior mediastinal lymph nodes are not separated by an anatomic
landmark that can be consistently identified radiologically or during surgery. Therefore, since the definition of PTLN can not uniformly be applied, studies
should be compared with some caution.
Because the status of the cervical lymph nodes is
the single most important tumor-related prognostic
factor, it is of great importance for optimal treatment
planning to know the exact involvement of all the cervical nodes. PTLN metastases may develop independently from lymph node metastases in other levels.
Plaat et al3 found clinically occult PTLN micrometastases in 4 of their 25 patients (16%) with laryngeal,
hypopharyngeal, and esophageal cancer. In the study
of Timon et al,4 5 of 13 patients with laryngeal, hypopharyngeal, and esophageal cancer with PTLN metastases had only PTLN metastases while the other
cervical lymph nodes were free of disease.
PTLN metastasis is a significant adverse prognostic factor. Rockley et al5 and Petrovic and Djordjevic6
identified PTLN metastases as a significant prognostic factor in patients undergoing laryngectomy. Joo et
al7 found that patients with hypopharyngeal cancer
and PTLN metastases have a high frequency of cervical metastasis at other levels and a poorer prognosis.
Plaat et al3 showed that PTLN metastasis with extranodal spread is an important adverse prognostic factor for disease-free and overall survival. PTLN
metastases carry a high risk for subsequent metastasis to the mediastinum and to distant sites.8 PTLN
metastases also have been linked to stomal recurrence after laryngectomy.4,9 Furthermore, the intraoperative diagnosis of metastasis in the thoracic PTLN
may also be used as an indicator for cervical lymph
node dissection in patients with middle and lower
thoracic esophageal cancer, as shown by Nagatani
et al,10 who found thoracic PTLN metastasis in 37%
of these patients. Half of them also had cervical
lymph node metastasis. Similar results where drawn
by Sato et al,11 who observed that PTLN metastasis
was the only independent factor for cervical lymph
node metastasis.
Paratracheal Lymph Node Dissection
If lymph node metastases are present, it is
obvious that treatment, usually lymph node dissection or irradiation, is warranted. However, management of clinically negative lymph nodes is
controversial. There is general agreement that elective treatment of the neck is indicated when there is
a high likelihood of occult (clinically undetectable)
lymph node metastases or when the patient will be
unavailable for regular or adequate follow-up. When
there is merely a high likelihood of occult lymph node
metastases, a choice must be made between elective
treatment and watchful waiting. These policies harbor
the risk of undertreatment and overtreatment affecting
survival and morbidity.
In the present review, advantages and disadvantages of elective or ‘‘routine’’ PTLN dissection are evaluated. These data are important for the development
of guidelines for performance of PTLN dissection.
Prevalence. The prevalence of PTLN metastasis differs in various reported series (Table 1).3,4,6,7,12–16 In a
study by Weber et al,12 29 of 141 patients (21%) with laryngeal, hypopharyngeal, and proximal esophageal
carcinomas had PTLN metastases. Timon et al4 found
PTLN metastases in 13 of 50 patients (26%) with
tumors at these sites. Shenoy et al13 found 9% ipsilateral PTLN metastases and 4.5% contralateral PTLN
metastases in patients with T3 or T4 glottic tumors
and tumor-positive necks. Petrovic and Djordjevic6
performed PTLN dissections for all T3 and T4 glottic
and subglottic cancers and found a prevalence of
PTLN metastases of 9%. Plaat et al3 found PTLN metastases in 20 of 85 patients (24%) who underwent
PTLN dissection for laryngeal or hypopharyngeal carcinoma. Joo et al7 reported a prevalence of ipsilateral
PTLN metastases in 14 of 64 patients (22%) who
underwent total laryngectomy for hypopharyngeal
carcinoma. Only 1 of 42 patients (1%) had contralateral PTLN metastasis.
The reported prevalence of PTLN metastases
varies according to the site and stage of the primary
tumor. Weber et al12 found PTLN metastases in 18%
of laryngeal carcinomas, 8% of hypopharyngeal carcinomas, and 71% of cervical esophageal carcinomas. In
patients with subglottic extension of laryngeal carcinoma, this figure was 27%. Timon et al4 found prevalences of 20% for laryngeal tumors and 43% for
cervical esophageal (including postcricoid) tumors. Surprisingly, none of the hypopharyngeal (excluding postcricoid) tumors had PTLN metastases. Other studies
report a lower prevalence of 9% in laryngeal carcinomas.6,13 Yang et al14 found PTLN metastases in only 1
of 92 patients (1%) with glottic carcinoma. This patient
was 1 of 21 patients (5%) with T3 and T4 glottic carcinoma.14 Garas and McGuirt16 found a PTLN prevalence of 27% in 15 patients with subglottic carcinoma.
In the study by Plaat et al,3 PTLN metastases were
present in 20% of the laryngeal tumors and in 35%
of the hypopharyngeal/cervical esophageal tumors.
HEAD & NECK—DOI 10.1002/hed
June 2011
913
T3-T4 tumors
22%
0%
20%
9%
27%
73%
0%
35%
43%
62%
T3-4 tumors
with Nþ
5% in T3-4 tumors
Mediastinal
dissection
Remarks
71%
8%
27%
67%
27%
12%
1%
18%
9%
64
2010
Paratracheal Lymph Node Dissection
Abbreviations: pro, prospective; retro, retrospective.
*All patients undergoing total laryngoesophagectomy and gastric transposition.
85
15
2005
2006
22%
Retro
þ
30%
Retro
Retro
þ
Pro
Retro
50
174
2003
2004
Timon et al4
Petrovic and
Djordjevic6
Plaat et al3
Garas and
McGuirt16
Joo et al7
26%
9%
þ*
Retro
Retro
92
34
1998
2001
Yang et al14
Martins15
1%
59%
þ
Retro
Pro
21%
9%
141
45
1993
1994
Weber et al12
Shenoy et al13
24%
27%
Cervical
esophagus
Hypopharynx
Subglottic
extension
Subglottic
Glottic
No.
Year
Authors
Metastasis
Prospective or
retrospective
Consecutive
Supraglottic
Larynx
Design
Total
Table 1. The reported prevalence of paratracheal lymph node metastases according to site and stage of the primary tumor.
914
Among supraglottic, glottic, and subglottic carcinomas,
the prevalence of PTLN metastases was 30%, 12%,
and 67%, respectively. Of the 37 patients with subglottic extension, 10 patients (27%) had PTLN metastases.3 Joo et al7 found a higher prevalence of ipsilateral
PTLN metastases in postcricoid carcinoma (57%) as
compared to pyriform sinus carcinoma (20%) and posterior pharyngeal wall carcinoma (8%). Martins15 analyzed the prevalence of PTLN in a series of squamous
cell carcinoma of the pharyngoesophageal junction.
Sixteen patients had esophageal carcinomas, 14 had
hypopharyngeal carcinomas, and 4 had laryngeal carcinomas. The mediastinal dissection was designed to
remove paratracheal and paraesophageal lymph nodes
down to the aortic arch, without thoracotomy. Mediastinal dissection data were available on 27 patients,
and 16 (59%) had mediastinal node metastasis. These
mediastinal nodes were positive in 0%, 73%, and 62%
of the patients with laryngeal, hypopharyngeal, and
esophageal carcinomas, respectively.
In most reported studies, PTLN dissection was
not routinely performed. Selection criteria for PTLN
dissection were usually not well defined. Therefore, in
most reported studies, selection bias may be presumed and results are difficult to compare.
Diagnostic Imaging. PTLN are not accessible to palpation. In patients with papillary thyroid carcinoma,
a sensitivity of only 35% and a specificity 85% is
reported for the detection of PTLN metastases by
ultrasonography.17 Preoperative evaluation of PTLN
by CT or MRI is difficult and limited in accuracy.18
Studies on the detection of (occult) PTLN metastases
are scarce. Ljumanovic et al19 considered nodes
located at the paratracheal level of 4 mm or greater
in smallest diameter on MRI as positive. Using this
criterion, positive PTLN appeared to be an independent prognostic factor for the development of distant
metastases.19 In the study by Joo et al,7 CT and/or
MRI detected 8 of 15 (53%) PTLN metastases in
patients with hypopharyngeal carcinoma.
The diagnostic modalities of ultrasound, CT, MRI,
and fluorodeoxyglucose-positron emission tomography
are not sufficiently reliable for the detection of occult
lymph nodes in the lateral neck (level I–V) to consider
negative examinations as justification not to treat the
lateral neck electively.20,21 It is likely that this also
holds true for the detection of occult PTLN metastases. However, in thoracic esophageal cancer, the diagnostic accuracy of PET/CT in the detection of
metastatic PTLN has been favorably compared to contrast-enhanced CT. Thus, the positive predictive value
of PET/CT was 93.8%, whereas that of CT was 62.5%.
The smallest lymph node metastasis detectable by
PET/CT was 6 mm, and CT revealed central necrosis in
only 27% of true-positive lymph nodes >1.8 cm.22
Sentinel node biopsy appears to be a reliable diagnostic technique for the detection of occult lymph node metastases in oral cancer.23 This sentinel node procedure
HEAD & NECK—DOI 10.1002/hed
June 2011
may also be suitable for laryngeal and hypopharyngeal
carcinomas: a PTLN dissection is only performed if a
sentinel PTLN is positive.24 However, in order to perform laryngectomy and PTLN dissection as a 1-stage
procedure, intraoperative examination of the sentinel
node is required. Alternatively, if lymphoscintigraphy after peritumoral injection of a radioactive tracer shows no
drainage to the PTLN, no dissection of these nodes is
required. Because of the limitations imposed by anatomic location and intraoperative logistics, practical
application of this modality to PTLN may be difficult.
Dissection. Depending on several factors, surgical
procedures harbor a risk of general and specific complications. The incidence and severity of complications
are linked to the extent of the operation. In PTLN dissection, injury to the pleura and lymphatic ducts, (tortuous) carotids, subclavian, and innominate arteries is
rare but may occur.2 Patients who undergo total laryngectomy have a high risk of fistula and other wound
healing problems. Patients who undergo bilateral
PTLN dissection have an increased risk of fistula. The
morbidity of fistula is increased by the removal of paratracheal tissue, with resultant exposure of great vessels at the root of the neck. Thus, PTLN dissection
may result in an increased risk of complications and
morbidity. Moreover, extending total laryngectomy
and neck dissection(s) with PTLN dissection results in
prolonged operating time with higher resource utilization and costs. The prevalence of hypothyroidism and
hypoparathyroidism after laryngectomy combined
with hemithyroidectomy and PTLN dissection is high.
The vascular supply of the remaining portion of the
thyroid gland may be injured during PTLN dissection,
which may contribute to the development of these
endocrinopathies. While this risk was not demonstrated in a study by Lo Galbo et al,25 it has been well
established that PTLN dissection is a significant factor
in producing postoperative hypocalcemia after thyroid
surgery.26
There are no generally recognized
guidelines for performing a PTLN dissection for laryngeal, hypopharyngeal, and cervical esophageal
cancer. As previously stated, the risk of occult metastases highly depends on the site, size, and extent of
the primary tumor. More reliable diagnostic imaging
for the detection of occult PTLN metastases is needed
for better selection of patients for PTLN dissection
and to avoid the morbidity, costs of resource utilization, and surgery in cancer-negative necks. However,
as the risks of complications and morbidity are limited, the decision to perform a PTLN dissection will
mainly depend on the risk of occult metastases, which
depends on the primary tumor site and results of diagnostic imaging techniques. Prospective studies with consecutive patients who undergo surgical treatment of
laryngeal, hypopharyngeal, and cervical esophageal
cancers with PTLN dissection as standard treatments
Guidelines.
Paratracheal Lymph Node Dissection
are needed to establish the ‘‘true’’ prevalence of PTLN
involvement. Based on these results, clinical guidelines
can be developed.
CONCLUSIONS
The limited morbidity of PTLN dissection and a
high rate of metastasis in specific laryngeal, hypopharyngeal, and cervical esophageal carcinomas
argue in favor of routine elective PTLN treatment.
These specific primary tumors probably include subglottic carcinoma, glottic carcinoma with subglottic
extension, transglottic, and hypopharyngeal carcinomas. Large prospective studies are needed to identify the patients with primary tumors at risk in
more detail. Moreover, improved diagnostic imaging
is needed to detect (occult) PTLN metastases more
reliably. Based on future studies, it is hoped that
clinical guidelines can be developed and undertreatment and overtreatment may be avoided.
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