secondary surgery of the neck for persistent or recurrent thyroid cancer ( tc ) is still the subject of debate .
the advocated extent of the salvage neck dissection ( nd ) has not been established yet .
subsequent procedure for the central compartment ( cc ) carries the risk related directly to the anatomy of this region .
upper mediastinum ( level vii ) and supraclavicular fossa ( level iv ) remains challenging even in the primary approach . in patients with tc , the balance between the risk of morbidity from secondary nd and the risk of untreated cancer disease still remains an unresolved issue .
previous articles have evaluated the feasibility and efficacy of reoperations in thyroid cancer ( in persistent or recurrent disease ) , but authors had focused on well differentiated thyroid cancer ( wdtc ) and surgeries limited to the central compartment [ 35 ] . in most cases , thyroid cancer recurrences in cervical lymph nodes can be visualized with ultrasound examination , what helps to arrange further therapeutic procedures .
the aim of the study was ( 1 ) to assess the feasibility of secondary neck dissections ( nd ) in well differentiated thyroid cancer , medullary cancer ( mtc ) and poorly differentiated thyroid cancer ( pdtc ) , ( 2 ) to evaluate the influence of nd extent on morbidity and ( 3 ) to describe the biochemical and clinical outcomes with special regard to lower neck levels ( iv , vi , vii ) .
the study group consisted of 51 consecutive patients with persistent / recurrent thyroid cancer ( 32 females and 19 males ) .
all patients enrolled to the study had been previously operated for tc in 11 different general surgery units and then followed - up in the department of endocrinology , metabolism and internal medicine of poznan university of medical sciences .
treatment failures had been subsequently referred to the department of otorhinolaryngology , head and neck surgery , poznan medical university .
the recurrent or persistent thyroid cancer neck disease was defined as : positive imaging on ultrasound , computed tomography or radioiodine whole body scan , increased thyroglobulin ( tg ) or calcitonin levels .
the age of the patients at the onset of disease ranged from 16 to 76  years ( mean 48  years ) .
46 patients had previously undergone one surgical procedure for tc and 5 patients two or more .
histological appearance of the primary lesion was determined according to the world health organization histological classification and was as follows : 33 cases of wdtc , 15 cases of mtc , 3 cases of pdtc .
staging was performed according to the american joint committee on cancer classification ( ajcc ) cancer staging manual revised in 2009 .
the advancement of the primary tumor was as follows : t1 in 6 cases , t2 in 16 cases , t3 in 18 cases and t4 in 11 cases .
nodal disease at the first presentation was n0 in 36 ( 60.8  % ) , and n+ in 15 ( 39.2  % ) patients respectively .
the time between the primary surgery and reoperation ranged from 7  months to 16  years ( median 2  years ) .
thyrotropin ( tsh ) stimulation had shown increased tg level ( > 2  ng / ml ) in 31/33 patients with wdtc .
the values ranged from 2.32 to  > 900  ng / ml . the supraphysiological thyroid hormone replacement was introduced in this group to achieve tsh suppression ( < 0.1 u / ml ) . in all patients with medullary cancer calcitonin level
was increased ( > 10  pg / ml ) and ranged from 13  pg / ml to over scale measurements > 480  pg / ml .
the indirect laryngoscopy and stroboscopy were performed before and after the reoperation ( on the 1st , 7th day and 6  months later if needed ) .
the mean follow - up time after the neck reoperation was 3.4    2.3  years .
vii neck levels . the choice of the procedure depended on rn advancement , macrometastases location and tumor histology .
the radical neck dissection ( rnd ) included the lateral node compartment : jugular chain nodes ( levels i , ii , iii , iv ) , posterior neck ( level v ) , from the skull base to the subclavian vein and laterally to the trapezius muscle . in all cases
the sternocleidomastoid muscle and jugular vein were dissected in strictly chosen cases ( in patients with lymph nodes metastases > 3  cm adjacent to the vessel wall ) .
selective neck dissection ( snd ) most often cleared levels iia , iii and iv .
dissection of the central compartment ( cc ) included level vi nodes extended vertically from the hyoid bone to the thoracic inlet and horizontally between the carotid sheaths ( prelaryngeal , pretracheal and paratracheal nodes ) .
the extension of the secondary nd and patients data concerning neck relapse are presented in table  1.table  1the types of thyroid cancer , localization of the excised nodes and the complications of secondary neck dissectionno.follow up time ( years)no . of complicationsrlnhpotherwdtc332.68126medullary cancer151.3383poorly differentiated thyroid cancer31.3222neck levels i  iii only62.7220neck level vi , vii only21111neck level iv only15000neck level iv , vi , vii+ other141.1685 
 total 

 51 

 1.8 

 13 

 22 

 11 

 rln recurrent laryngeal nerve injury ( both persistent and transient ) , hp persistent hypoparathyroidism the types of thyroid cancer , localization of the excised nodes and the complications of secondary neck dissection 
 rln recurrent laryngeal nerve injury ( both persistent and transient ) , hp persistent hypoparathyroidism rnd was performed in 22 patients ( 43.1  % ; 15-wdtc , 6-mtc , 1-pdtc ) and snd in 29 patients ( 56.9  % ; 18-wdtc , 9-mtc , 2-pdtc ) .
cc ( level vi ) was cleaned in 14 patients ( 27.5  % ; 9-wdtc , 4-mtc , 1-pdtc)in two as the main procedure and in 12 as complementary to lateral node compartment dissection .
level vii ( upper mediastinal nodes ) were dissected in 10 patients ( 19.6  % ; 7-wdtc , 1-mtc , 2-pdtc ) , levels i , ii , iii , iv and v in 3 , 36 , 40 , 41 and 21 patients respectively . all together
lower neck reoperation ( iv , vi , vii ) was performed in 46 cases ( 90.2  % ) .
11 patients were operated more than once ( 4 patients with wdtc , 6-mtc , 1-pdtc ) .
total amount of neck dissections was 66 . in our study group the localization of recurrence ( level i  iii , iv , v , vi , vii ) and the time between the primary surgery and the recurrence did not depend on patients gender , age or the type of thyroid cancer . in three patients very aggressive
course of the recurrent disease was observed : in two cases gross infiltration of the larynx and esophagus requiring total laryngectomy with partial esophagectomy .
the number of removed lymph nodes ranged from 1 to 42 . in the majority of patients
data of the neck dissection specimens including number of metastatic nodes end extracapsular spread ( ecs ) was presented in table  2.table  2histopathological results of the neck dissection specimenneck levelno . of nodes removedno . of patientspn+ecsi / ii / iii only34680iv
only1111iv , vi , vii + other16714946vi , vii only112101 
 ecs extra capsular spread histopathological results of the neck dissection specimen 
 ecs extra capsular spread the number of metastatic nodes ranged from 1 to 28 .
single metastatic lymph nodes were found in 11 patients ( 21.6  % ) , 2 metastatic lymph nodes in 10 patients ( 19.6  % ) , three in 1 patient ( 2  % ) , 4 in 3 patients ( 5.9  % ) and 5 or more in 25 patients ( 47.1  % ) .
metastases were confirmed in all 14 cc and all 10 mediastinal specimens ; thus in levels vi and vii there were no false negative results .
out of 59 lateral neck specimens metastases were found in the levels ii and iii in 37 cases ( 72  % ) and in the level iv in 35 cases ( 68  % ) .
the occurrence of bilateral metastases did not depend on the type of thyroid cancer , but was often observed in younger patients ( p  =  0.07 ) and in patients with primary surgery performed at younger age ( p  =  0.049 ) .
furthermore , these two groups more frequently required radical neck dissection ( p  <  0.01 in both groups ) . in six specimens from the viith level
the technical difficulties included disturbed anatomy , scars , infiltration of subclavicular vessels or of the junction between subclavian and internal jugular vein ( 5 patients ) , infiltration of the larynx or esophagus ( 2 patients ) , infiltration of trachea ( 1 patient ) .
postoperative vocal cord paresis was observed in 13 ( 25.5  % ) , transient in 5 ( 9.8  % ) , permanent in 8 ( 15.7  % ) patients . in seven patients recurrent laryngeal nerve ( rln )
was injured due to direct tumor invasionin three ( mtc ) nerve was intentionally sectioned and in four ( wdtc ) nerve was detached from the tumor . in six patients rln visualization was impossible due to rigidity of the scar tissue ; paresis occurred postoperatively .
six patients suffered from severe dyspnoea : in three laterofixation and in three emergency tracheotomy was indispensable .
permanent tracheostomy was maintained in five ( 9.8  % ) patients : in three with vocal cord paresis and in two after laryngectomy .
four patients had postoperative chyle leakage : in two cases low output , stopped after conservative treatment after 68  days , in one patient high - output leak was controlled on the 5th day by direct ligation . in the 4th case
the patient suffered from chylothorax , required two reoperations , that occurred unsuccessful and the patient expired on the 36th day .
massive bleeding occurred intraoperatively in three patients ( in one from common carotid artery , in two from the stump of internal jugular vein ) .
one patient died due to massive bleeding from common carotid artery on the 2nd day after surgery .
the postoperative pth serum level was within the normal range ( 1565  pg / ml ) in 30 ( 58.8  % ) patients . however , hypocalcaemia requiring vitamin d and/or calcium supplementation appeared in 22 patients ( 43.1  % ) .
it is important to note , that 8 out of 14 patients operated on iv , vi , vii levels developed hypoparathyroidism ( 57  % ) .
there was no correlation between the rate of complications and patients age , gender , time from primary surgery or cancer histology .
furthermore , the number of dissected lymph nodes and the presence of bilateral metastatic changes also did not influence significantly the frequency of complications .
secondary nd performed in the left subclavian or in the upper mediastinal area were connected with gross complications : 5/8 cases of rln paresis , 2 chyle leakage and 1 chylothorax and 2 massive bleedings .
two of the patients had perioperative complications and expired soon after the procedure ( 2nd and 36th day)both with wdtc .
out of the other patients with wdtc : one patient died of disseminated tc 2  years after neck dissection , at age of 74  years ; two patients ( 6  % ) developed new recurrence in the upper mediastinum , not qualifying for the additional nd , 5 patients ( 15.2  % ) developed lung metastases and one bone metastases ( 3  % ) .
seven patients ( 21.2  % ) indicated biochemical cure at the first control examination after the reoperative surgery ( tg level < 2  ng / ml evaluated on thyrotropin stimulation ) , in ten patients tg was < 2  ng / ml in the follow - up ( 30.3  % ) , in six patients ( 18.2  % ) tg level decreased after operation .
seven patients ( 21  % ) still presented with notably elevated tg levels > 30  ng / ml . none of the patients with mtc achieved calcitonin level lower than 10  pg / ml .
nine patients developed distant metastases in 1016  months time ( lung metastases in 7 patients , bone metastases in 3 patients ) .
none of the patients with poorly differentiated thyroid cancer achieved tg level < 2  ng / ml ) .
one patient developed disseminated lung and bone metastases and is still under control of our clinic ( 4  years after neck dissection ) .
distant metastases were observed more frequently in patients with mtc and pdtc ( p  =  0.007 ) .
the number of removed lymph nodes ranged from 1 to 42 . in the majority of patients metastatic tc was present in multiple nodes .
data of the neck dissection specimens including number of metastatic nodes end extracapsular spread ( ecs ) was presented in table  2.table  2histopathological results of the neck dissection specimenneck levelno .
of nodes removedno . of patientspn+ecsi / ii / iii only34680iv only1111iv , vi , vii + other16714946vi , vii only112101 
 ecs extra capsular spread histopathological results of the neck dissection specimen 
 ecs extra capsular spread the number of metastatic nodes ranged from 1 to 28 .
single metastatic lymph nodes were found in 11 patients ( 21.6  % ) , 2 metastatic lymph nodes in 10 patients ( 19.6  % ) , three in 1 patient ( 2  % ) , 4 in 3 patients ( 5.9  % ) and 5 or more in 25 patients ( 47.1  % ) .
metastases were confirmed in all 14 cc and all 10 mediastinal specimens ; thus in levels vi and vii there were no false negative results .
out of 59 lateral neck specimens metastases were found in the levels ii and iii in 37 cases ( 72  % ) and in the level iv in 35 cases ( 68  % ) .
the occurrence of bilateral metastases did not depend on the type of thyroid cancer , but was often observed in younger patients ( p  =  0.07 ) and in patients with primary surgery performed at younger age ( p  =  0.049 ) .
furthermore , these two groups more frequently required radical neck dissection ( p  <  0.01 in both groups ) . in six specimens from the viith level
the technical difficulties included disturbed anatomy , scars , infiltration of subclavicular vessels or of the junction between subclavian and internal jugular vein ( 5 patients ) , infiltration of the larynx or esophagus ( 2 patients ) , infiltration of trachea ( 1 patient ) .
postoperative vocal cord paresis was observed in 13 ( 25.5  % ) , transient in 5 ( 9.8  % ) , permanent in 8 ( 15.7  % ) patients . in seven patients recurrent laryngeal nerve ( rln )
was injured due to direct tumor invasionin three ( mtc ) nerve was intentionally sectioned and in four ( wdtc ) nerve was detached from the tumor . in six patients rln visualization was impossible due to rigidity of the scar tissue ; paresis occurred postoperatively .
six patients suffered from severe dyspnoea : in three laterofixation and in three emergency tracheotomy was indispensable .
permanent tracheostomy was maintained in five ( 9.8  % ) patients : in three with vocal cord paresis and in two after laryngectomy .
four patients had postoperative chyle leakage : in two cases low output , stopped after conservative treatment after 68  days , in one patient high - output leak was controlled on the 5th day by direct ligation . in the 4th case the patient suffered from chylothorax , required two reoperations , that occurred unsuccessful and the patient expired on the 36th day .
massive bleeding occurred intraoperatively in three patients ( in one from common carotid artery , in two from the stump of internal jugular vein ) .
one patient died due to massive bleeding from common carotid artery on the 2nd day after surgery .
the postoperative pth serum level was within the normal range ( 1565  pg / ml ) in 30 ( 58.8  % ) patients . however , hypocalcaemia requiring vitamin d and/or calcium supplementation appeared in 22 patients ( 43.1  % ) .
it is important to note , that 8 out of 14 patients operated on iv , vi , vii levels developed hypoparathyroidism ( 57  % ) .
there was no correlation between the rate of complications and patients age , gender , time from primary surgery or cancer histology .
furthermore , the number of dissected lymph nodes and the presence of bilateral metastatic changes also did not influence significantly the frequency of complications .
secondary nd performed in the left subclavian or in the upper mediastinal area were connected with gross complications : 5/8 cases of rln paresis , 2 chyle leakage and 1 chylothorax and 2 massive bleedings .
two of the patients had perioperative complications and expired soon after the procedure ( 2nd and 36th day)both with wdtc .
out of the other patients with wdtc : one patient died of disseminated tc 2  years after neck dissection , at age of 74  years ; two patients ( 6  % ) developed new recurrence in the upper mediastinum , not qualifying for the additional nd , 5 patients ( 15.2  % ) developed lung metastases and one bone metastases ( 3  % ) .
seven patients ( 21.2  % ) indicated biochemical cure at the first control examination after the reoperative surgery ( tg level < 2  ng / ml evaluated on thyrotropin stimulation ) , in ten patients tg was < 2  ng / ml in the follow - up ( 30.3  % ) , in six patients ( 18.2  % ) tg level decreased after operation .
seven patients ( 21  % ) still presented with notably elevated tg levels > 30  ng / ml . none of the patients with mtc achieved calcitonin level lower than 10  pg / ml .
nine patients developed distant metastases in 1016  months time ( lung metastases in 7 patients , bone metastases in 3 patients ) .
none of the patients with poorly differentiated thyroid cancer achieved tg level < 2  ng / ml ) .
one patient developed disseminated lung and bone metastases and is still under control of our clinic ( 4  years after neck dissection ) .
distant metastases were observed more frequently in patients with mtc and pdtc ( p  =  0.007 ) .
the american thyroid association ( ata ) and national comprehensive cancer network ( nccn ) recommends treatment options for recurrent or persistent wdtc : radioiodine therapy for radioiodine sensitive disease and surgery for clinically significant disease .
secondary surgery in cc has been approved in the literature [ 4 , 9 , 10 ] , although is associated with high risk of complications and moderate possibilities of tumor eradication . therefore , the question is , how to obtain the balance between the cure and complication rates and whether the patient will benefit from the surgery . in patients with medullary cancer
the sites frequently involved in recurrent or persistent disease include retrocarotid nodes , nodes deep to laryngeal recurrent nerve , retroclavicular nodes , retrosternal nodes and nodes running along the superior thyroid vascular pedicle medial to the carotid bifurcation .
leaving positive nodes in tracheoesophageal groove may expose the patient to risk of tracheal , esophageal or even laryngeal invasion .
.   found nodal metastases in central and bilateral central compartment in 86.7 and 42.2  % cases respectively but little attention was devoted to the neighboring iv level .
metastasizing pattern in our group revealed pn+ in level iv , vi and vii in 41 , 16 and 10 patients respectively ; in the ivth level over 70  % , in cc 100  % of taken nodes were pn+ ; 17  % of patients had metastases bilaterally .
comparing primary and recurrent disease distribution stated , that there was no difference in frequency in levels i , ii , iii and v but level iv was more common in the recurrent cases . salvage neck surgery in our group confirmed the necessity of clearing all lower neck basins . in our group
it is important to confront the surgical feasibility and morbidity in patients with recurrences in the lower neck anatomical region .
the previous studies demonstrated that there is no additional morbidity in secondary procedures and complication rate is similar to initial surgical procedure , if performed by experienced surgeon [ 2 , 14 ] .
numerous authors described the cc salvage surgery as safe and efficient oncological procedure exhibiting minimal morbidity [ 1 , 4 , 5 , 10 , 15 ] . on the other hand ,
hartl and travagli   underlined additional morbidity when central nd is performed as secondary procedure .
although the boundaries and the anatomical structures that require dissection are the same , the scar tissue and neovascularization complicates the access to this region ; the sternohyoid and sternothyroid muscles are adherent to the trachea in dense scar tissue .
thus , reoperative surgery of the cc is associated with higher risk of vocal folds paresis . according to mirghani
cc nd can be performed with minimal morbidity , when recurrent laryngeal nerve is not invaded . in our group in 3/15 medullary cancers the nerve was intentionally sectioned , in 4/33 wdtc detached from the tumor . in eight cases ( 15.7  % )
permanent vocal cord paresis was observed ; in three ( 5.9  % ) tracheotomy had to be maintained .
it has been stated , that parathyroid glands are at increased risk for injury and permanent hypoparathyroidism is the most common adverse event in cc secondary surgery .
permanent hypoparathyroidism has been reported to range between 2.7   and 9  % . in our study
long - term follow - up revealed permanent hypoparathyroidism in 22 patients ( 43.1  % ) .
the outcomes of reoperative surgery for wdtc can be categorized as the absence of biochemical disease or clinically detectable disease . in our center
the required tg level assessed on tsh stimulation was determined to be lower than 2  ng / ml . according to hughes et al .  
biochemical complete response obtained in 26  % of patients may be concentrated on locoregional control of disease to prevent complications due to local invasion rather than elimination of biochemically active cancer . in our study
stimulated tg < 2  mg / ml was observed in seven patients with wdtc directly after reoperative procedure ( 21.2  % ) and in ten patients in the follow - up ( 30.3  % ) .
six patients with wdtc developed distant metastases . in mtc or pdtc the final results of secondary surgery were poor .
none of the patients with mtc achieved calcitonin level lower than 10  pg / ml and none of the patients with pdtc achieved biochemical remission .
it should be therefore concluded , that mtc and pdtc need more rigorous preoperative work up to ensure that distant metastases are excluded , otherwise the prognosis will be unfavorable despite successful neck dissection .
our study reports the large cohort of patients undergoing secondary nd due to thyroid cancer .
surgical approach and possibility of complications in this group present a challenge . in mtc and
pdtc the long - term results were unsatisfactory ( calcitonin / tg still elevated , frequent distant metastases ) . in wdtc the secondary neck dissection should be performed in cases in which there are strong indications for surgical procedure .
metastases localization in levels vi , vii , iv was connected with high complication rate . on the other hand total clearance of these basins proved to be crucial for the satisfactory oncological outcomes .
 the purpose of the study was to assess the feasibility of secondary neck dissections ( nd ) in different types of thyroid cancer ( tc ) , to evaluate the influence of nd extent on morbidity and to describe biochemical and clinical outcomes . 
 51 patients previously operated for tc ( 33-well differentiated tc - wdtc , 15 medullary tc - mtc , 3 poorly differentiated tc - pdtc ) presenting detectable nodal disease . 
 reoperations covered i  vii neck levels . 
 radical neck dissection was performed in 22 patients , selective neck dissection in 29 patients . 
 14 central compartment ( cc ) , 10 mediastinal and 41 level iv excisions were performed . 
 postoperative complications occurred in 13 patients : 4 chyle leaks , 3 massive bleedings , 8 permanent vocal cord pareses , hypoparathyroidism in 22 patients ( 43.1  % ) , 2 patients expired in perioperative period . in wdtc : in seven patients thyroglobulin level normalized directly after nd , in ten patients in the follow - up ; six patients developed distant metastases . 
 none of the patients with mtc achieved calcitonin level < 10  pg / ml ; nine patients developed distant metastases . 
 none of the patients with pdtc achieved tg < 2  mg / ml ; two patients died , the third developed distant metastases . 
 secondary nd in tc present a challenge by means of surgical approach and possibility of complications . in mtc and 
 pdtc the long - term results were unsatisfactory . 
 in wdtc , the secondary nd should be performed due to strong indications . 
 metastases localization in levels iv , vi , vii were connected with high complication rate , but these surgeries were crucial for satisfactory oncological outcomes . 
Introduction
Materials and methods
Results
Histopathological findings
Complications and morbidity
Outcomes of secondary nodal surgery
Discussion