- Email: [email protected]
Biopsy of the sentinel node in lung cancer
G Model
ARTICLE IN PRESS Med Clin (Barc). 2017;xxx(xx):xxx–xxx
www.elsevier.es/medicinaclinica
Brief report
Biopsy of the sentinel node in lung cancer夽 Naia Uribe-Etxebarria Lugariza-Aresti a,∗ , Ramón Barceló Galíndez b , Joaquín Pac Ferrer a , Jaime Méndez Martín c , Jose Genollá Subirats d , Juan Casanova Viudez a a
Servicio de Cirugía Torácica, Hospital Universitario de Cruces, Barakaldo, Vizcaya, Spain Servicio de Oncología Médica, Hospital Universitario de Basurto, Bilbao, Vizcaya, Spain Servicio de Cirugía General, Hospital Universitario de Basurto, Bilbao, Vizcaya, Spain d Servicio de Medicina Nuclear, Hospital Universitario de Cruces, Barakaldo, Vizcaya, Spain b
c
a r t i c l e
i n f o
Article history: Received 30 May 2016 Accepted 13 October 2016 Available online xxx Keywords: Sentinel node Lung cancer Micrometastasis Skip metastases
a b s t r a c t Introduction and objective: Mediastinal lymph node involvement can be understaged in cases of lung cancer (up to 20% in stage i). Sentinel node detection is a standard technique recommended in breast cancer and melanoma action guidelines, and could also be useful in cases of lung cancer. Material and methods: Considering the detection of the sentinel node in non-small cell lung cancer (NSCLC) as feasible, a prospective cohort study was carried out on 48 patients with resectable NSCLC, using the intraoperative injection of colloid sulphate technetium-99. Results: The radioisotope migrated in all cases. The procedure’s sensitivity was 88.24%, its accuracy was 95.83%, its negative predictive value was 93.94% and the false negative rate was 11.76%. No complications were associated with this technique. Conclusions: The detection of a sentinel node in NSCLC with the intraoperative injection of the isotope is feasible and safe, and allows for detection and sensitivity rates comparable to those of other tumor types. ˜ S.L.U. All rights reserved. © 2016 Elsevier Espana,
Biopsia del ganglio centinela en el cáncer de pulmón r e s u m e n Palabras clave: Ganglio centinela Cáncer de pulmón Micrometástasis Skip metástasis
Introducción y objetivo: En el cáncer de pulmón la afectación ganglionar mediastínica puede estar infraestadificada (hasta en el 20% de los casos en estadios i). La detección del ganglio centinela es una técnica estándar en las guías de actuación del cáncer de mama y melanoma y podría ser útil en el cáncer de pulmón. Material y métodos: Con la hipótesis de que es factible la detección del ganglio centinela en el cáncer de ˜ (CPCNP) resecable, se realizó un estudio de cohortes prospectivo en 48 pulmón de células no pequenas pacientes con CPCNP resecables utilizando la inyección intraoperatoria de tecnecio 99 sulfato coloide. Resultados: El radioisótopo migró en todos los casos. La sensibilidad de la prueba es del 88,24% y la precisión del 95,83%, con un valor predictivo negativo del 93,94% y una tasa de falsos negativos del 11,76%. No existieron complicaciones relacionadas con la técnica. Conclusiones: La detección del ganglio centinela en el CPCNP con inyección intraoperatoria de isótopos es factible y segura, y permite tasas de detección y sensibilidad superponibles a las de otros tipos de tumor. ˜ S.L.U. Todos los derechos reservados. © 2016 Elsevier Espana,
Introduction 夽 Please cite this article as: Uribe-Etxebarria Lugariza-Aresti N, Barceló Galíndez R, Pac Ferrer J, Méndez Martín J, Genollá Subirats J, Casanova Viudez J. Biopsia del ganglio centinela en el cáncer de pulmón. Med Clin (Barc). 2017. http://dx.doi.org/10.1016/j.medcli.2016.10.034 ∗ Corresponding author. E-mail address: [email protected] (N. Uribe-Etxebarria Lugariza-Aresti).
The detection of the sentinel node, defined as the initial lymph node drainage node from the tumor,1 has become a standard technique in the action guides for breast cancer and melanoma,2,3 improving the accuracy of extension diagnosis and influencing in the choice of later treatments.
˜ S.L.U. All rights reserved. 2387-0206/© 2016 Elsevier Espana,
MEDCLE-3842; No. of Pages 3
G Model 2
ARTICLE IN PRESS N. Uribe-Etxebarria Lugariza-Aresti et al. / Med Clin (Barc). 2017;xxx(xx):xxx–xxx
Mediastinal lymphadenectomy is a standard of low morbidity to increase the accuracy of extension diagnosis. However, infrastaging, which may be up to 20% in stages I, suggests that sentinel lymph node detection techniques in non-small cell lung cancer (NSCLC)4 may be useful. This prospective cohort study was conducted with the hypothesis that it is feasible to detect the sentinel node in the resectable NSCLC using the injection of technetium 99 colloid sulfate at the intraoperative time, and that would provide improvements in tumor staging, with its corresponding influence in therapeutic programs and prognostic boundaries.
Pathological examination It was performed on a deferred basis. Lymph nodes were initially examined with conventional sections using hematoxylin-eosin stains. If these studies were tumor-negative, additional studies were performed on sentinel lymph nodes using serial cuts with intervals of 30 m and IHC with cytokeratin antibodies CK7 and CK20 and TTF1. IHC was considered positive if cell accumulation or individual positive cells were demonstrated with an appropriate cell morphology compatible with tumor cells.
Results Patients and methods Approved by the Research Committee and the Ethics Committee of Cruces Hospital, the study followed the ethical principles of the Helsinki Declaration (as amended at the 59th Seoul General Assembly). People included were informed about the characteristics and the technique of the study, authorizing the same through informed consent prior to the procedure.
Patient selection 52 patients with suspected NSCLC in stage i-iiA or clinical i-iiB (T1-T2, N0 or N1, preoperative M0) were included according to TNM7. Thirty-two patients had a preoperative pathological diagnosis of NSCLC; in 18 patients without preoperative diagnosis, NSCLC was confirmed by intraoperative tumor biopsy performed after radionuclide injection. Four patients were excluded: in 2 the technique could not be performed since the tumor was very central and it did not allow to complete the puncture in its 4 quadrants. In another 2 patients the diagnosis of NSCLC was ruled out. However, in these cases there was also evidence of radionuclide migration. Therefore, 48 patients were included in the study: 41 males (85.41%) and 7 females (14.58%). The mean age of the series was 64.60 ± 7.97 years, with an age range of 43–80 years. According to TNM7, the preoperative stage of the patients was: 20 cases in stage IA (8 T1aN0M0; 12 T1bN0M0), 23 in stage IB (T2aN0M0), 4 in stage IIA (2 T1aN1M0, one T1bN1M0, one T2aN1M0) and one in stage IIIA (T3N1M0).
Sentinel node detection technique
The radioisotope migrated in all 48 cases. In 44 patients, a single sentinel node was located and in 4 patients, 2 were located, 52 sentinel lymph nodes in total. Sentinel lymph nodes were located primarily near the tumor. 61.53% were intercisural and 34.61% were hilar. 3.84% were mediastinal. In 2 patients (4.17%) the first lymph node drainage station was in mediastinal ganglia (skip phenomenon), stations 5 and 6, in 2 tumors of the upper left lobe. The histology of the resected tumors was: 28 adenocarcinomas (3 bronchioalveolar), 15 epidermoids, 2 adenosquamous, 1 undifferentiated and 2 carcinoids. When comparing preoperative and postsurgical N stage (see Table 1), 9 patients increased their stage: 5 patients from stage N0 to N1, 2 patients from N0 to N2 and 2 patients from N1 to N2. Two patients decreased their stage: from N1 to N0. Histological studies revealed metastatic dissemination in 16 of the 52 sentinel lymph nodes examined (30.76%): 8 in intercisional sentinel nodes and 8 in hilar sentinel nodes. In 9 patients (18.75%) the only adenopathy presenting with metastasis was the sentinel node. With the use of IHQ techniques, 2 micrometastases (one hilar and one intercisural) were detected, which were not diagnosed by routine anatomic pathology. Therefore, 2 patients (6.45% of the N0 patients) were staged again as N1. There were no complications related to the sentinel node technique or mortality in the series. The sensitivity of the test was 88.24% (false negative rate 11.76%) and accuracy was 95.83%, with a negative predictive value of 93.94%. Overall survival at 5 years is 56.25%. It is detailed by stages in Table 2.
Table 1 Preoperative-postsurgical stage. Preoperative
For each of the cases, a dose of technetium 99 colloid sulphate of 9.25 MBq divided into 4 syringes of 1 ml was prepared under sterile techniques. The radioisotope was injected at the periphery of the 4 quadrants of the tumor. The minimum time for migration of injected technetium to the lymph nodes was 10 min. The readings were performed with a manual gamma radiation counter with a sterile plastic cover on the reader. Two readings were obtained: in vivo (without drying the piece) and ex vivo (once the piece was resected). Standardized tumor resection was performed together with the resection of the visible mediastinal, peribronchial and hilar lymph nodes. Subsequently, the ex vivo measurement was performed. All those that had a radioactivity 3 times greater than the baseline value of the patient were considered as sentinel lymph nodes. After standard anatomical resection and nodal mediastinal dissection, the thoracic cavity was again inspected with the gamma meter to verify that there was no residual radiation or nodes not detected previously.
Postoperative
T1aN0M0
8
T1bN0M0
12
T1aN1M0
2
T1bN1M0 T2aN0M0
1 23
T2aN1M0 T3N1M0
1 1
T1aN0M0 T1bN0M0 T1bN1M0 T2aN0M0 T2bN1M0 T1aN0M0 T2aN0M0 T2aN1M0 T3N0M0 T1aN1M0 T2aN2M0 T1bN0M0 T1aN1M0 T2aN0M0 T2bN0M0 T2aN1M0 T2aN2M0 T3N0M0 T4N2M0 T2aN0M0 T4N2M0
2 1 2 2 1 1 8 1 2 1 1 1 1 10 2 5 3 1 1 1 1
G Model
ARTICLE IN PRESS N. Uribe-Etxebarria Lugariza-Aresti et al. / Med Clin (Barc). 2017;xxx(xx):xxx–xxx
Table 2 Survival by stages. IA
80%
IB IIA
71.42%
IIB
41.66%
IIIA IIIB
0% 0%
T1aN0M0 T1bN0M0 T2aN0M0 T2bN0M0 T1aN1M0 T1bN1M0 T2aN1M0 T2bN1M0 T3N0M0 T2aN2M0 T4N2M0
66.66% 100% 71.42% 50% 50% 50% 33.33% 0% 100% 0% 0%
Discussion The detection of sentinel node in NSCLC with intraoperative injection of isotopes is feasible and safe.5 In the published series, high test accuracy is appreciated, with a sensitivity of more than 80% for the use of isotope or isotope plus dye, and it does not appear to be a complicated technique to learn and apply.6 However, a multicenter phase II trial did not achieve its selection goal, with a very low sensitivity, apparently due to logistical problems.7 This prospective cohort study is a validation analysis of the technique of sentinel node detection in NSCLC by injection of technetium 99 sulphate colloid, in which it is seen as a feasible, safe and relatively simple technique. Our results, in line with those of other series, with similar precision and sensitivity, point in favor of studying the sentinel node in operable lung cancer. It seems to us to be especially important the greater accuracy in staging (detection of micrometastasis) and the detection of skip-mediastinal metastasis that may have importance in the treatment and prognosis of the patients. We detected the presence of skip metastasis in a smaller amount than in other series, where it was reached up to 33%, probably due to the characteristics of the patients included. Due to legal limitations with the use of isotopes, in Japan they studied the injection of the isotope in a preoperative peritumoral rather than intraoperative manner, with very similar results.8 Intratumoral injection, on the other hand, seems inferior when establishing lymphatic drainage from the diseased area. Some groups have used radiopaque films to remove noise from the injected area but in general, in vivo and ex vivo detection allows localization of drainage nodes from the primary tumor.
3
The use of technetium 99 with or without dye is the most established technique. In the near future it is expected to include novelties, such as magnetic materials,9 fluorescent dyes,10 TAC contrast agents and carbon nanoparticles. In conclusion, the techniques of detection of sentinel node in lung cancer with technetium 99 allow detection rates and a sensitivity superimposable to those of other types of tumor. Conflict of interests The authors declare that they have no conflict of interest. References 1. Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA, Storm FK, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127:392–9. 2. Gershenwald JE, Thompson W, Mansfield PF, Lee JE, Colome MI, Tseng CH, et al. Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage i or ii melanoma patients. J Clin Oncol. 1999;17:976–83. 3. Veronesi U, Paganelli G, Viale G, Galimberti V, Luini A, Zurrida S, et al. Sentinel lymph node biopsy and axillary dissection in breast cancer: results in a large series. J Natl Cancer Inst. 1999;91:368–73. 4. Kubuschock B, Passlick B, Izbicki JR, Thetter O, Pantel K. Disseminated tumor cells in lymph nodes as a determinant for survival in surgically resected non-small cell lung cancer. J Clin Oncol. 1999;17:19–24. 5. Liptay MJ, Grondin S, Fry WA, Pozdol C, Carson D, Knop C, et al. Intraoperative sentinel lymph node mapping in non-small cell lung cancer improves detection of micrometastasis. J Clin Oncol. 2002;20: 1984–8. 6. Taghizadeh Kermani A, Bagheri R, Tehranian S, Shojaee P, Sadeghi R, Krag DN. Accuracy of sentinel node biopsy in the staging of non-small cell lung carcinomas: systematic review and meta-analysis of the literature. Lung Cancer. 2013;80:5–14. 7. Liptay MJ, D’amico TA, Nwogu C, Demmy TL, Wang XF, Gu L, et al. Intraoperative sentinel node mapping with technitium-99 in lung cancer: results of CALGB 140203 multicenter phase ii trial. J Thorac Oncol. 2009;4: 198–202. 8. Nomori H, Horio H, Naruke T, Orikasa H, Yamazaki K, Suemasu K. Use of technetium-99 m tin colloid for sentinel lymph node identification in non-small cell lung cancer. J Thorac Cardiovasc Surg. 2002;124:486–92. 9. Minamiya Y, Ito M, Katayose Y, Saito H, Imai K, Sato Y, et al. Intraoperative sentinel lymph node mapping using a new sterilizable magnetometer in patients with nonsmall cell lung cancer. Ann Thorac Surg. 2006;81:327–30. 10. Yamashita S, Tokuishi K, Miyawaki M, Anami K, Moroga T, Takeno S, et al. Sentinel node navigation surgery by thoracoscopic fluorescence imaging system and molecular examination in non-small cell lung cancer. Ann Surg Oncol. 2012;19:728–33.
ARTICLE IN PRESS Med Clin (Barc). 2017;xxx(xx):xxx–xxx
www.elsevier.es/medicinaclinica
Brief report
Biopsy of the sentinel node in lung cancer夽 Naia Uribe-Etxebarria Lugariza-Aresti a,∗ , Ramón Barceló Galíndez b , Joaquín Pac Ferrer a , Jaime Méndez Martín c , Jose Genollá Subirats d , Juan Casanova Viudez a a
Servicio de Cirugía Torácica, Hospital Universitario de Cruces, Barakaldo, Vizcaya, Spain Servicio de Oncología Médica, Hospital Universitario de Basurto, Bilbao, Vizcaya, Spain Servicio de Cirugía General, Hospital Universitario de Basurto, Bilbao, Vizcaya, Spain d Servicio de Medicina Nuclear, Hospital Universitario de Cruces, Barakaldo, Vizcaya, Spain b
c
a r t i c l e
i n f o
Article history: Received 30 May 2016 Accepted 13 October 2016 Available online xxx Keywords: Sentinel node Lung cancer Micrometastasis Skip metastases
a b s t r a c t Introduction and objective: Mediastinal lymph node involvement can be understaged in cases of lung cancer (up to 20% in stage i). Sentinel node detection is a standard technique recommended in breast cancer and melanoma action guidelines, and could also be useful in cases of lung cancer. Material and methods: Considering the detection of the sentinel node in non-small cell lung cancer (NSCLC) as feasible, a prospective cohort study was carried out on 48 patients with resectable NSCLC, using the intraoperative injection of colloid sulphate technetium-99. Results: The radioisotope migrated in all cases. The procedure’s sensitivity was 88.24%, its accuracy was 95.83%, its negative predictive value was 93.94% and the false negative rate was 11.76%. No complications were associated with this technique. Conclusions: The detection of a sentinel node in NSCLC with the intraoperative injection of the isotope is feasible and safe, and allows for detection and sensitivity rates comparable to those of other tumor types. ˜ S.L.U. All rights reserved. © 2016 Elsevier Espana,
Biopsia del ganglio centinela en el cáncer de pulmón r e s u m e n Palabras clave: Ganglio centinela Cáncer de pulmón Micrometástasis Skip metástasis
Introducción y objetivo: En el cáncer de pulmón la afectación ganglionar mediastínica puede estar infraestadificada (hasta en el 20% de los casos en estadios i). La detección del ganglio centinela es una técnica estándar en las guías de actuación del cáncer de mama y melanoma y podría ser útil en el cáncer de pulmón. Material y métodos: Con la hipótesis de que es factible la detección del ganglio centinela en el cáncer de ˜ (CPCNP) resecable, se realizó un estudio de cohortes prospectivo en 48 pulmón de células no pequenas pacientes con CPCNP resecables utilizando la inyección intraoperatoria de tecnecio 99 sulfato coloide. Resultados: El radioisótopo migró en todos los casos. La sensibilidad de la prueba es del 88,24% y la precisión del 95,83%, con un valor predictivo negativo del 93,94% y una tasa de falsos negativos del 11,76%. No existieron complicaciones relacionadas con la técnica. Conclusiones: La detección del ganglio centinela en el CPCNP con inyección intraoperatoria de isótopos es factible y segura, y permite tasas de detección y sensibilidad superponibles a las de otros tipos de tumor. ˜ S.L.U. Todos los derechos reservados. © 2016 Elsevier Espana,
Introduction 夽 Please cite this article as: Uribe-Etxebarria Lugariza-Aresti N, Barceló Galíndez R, Pac Ferrer J, Méndez Martín J, Genollá Subirats J, Casanova Viudez J. Biopsia del ganglio centinela en el cáncer de pulmón. Med Clin (Barc). 2017. http://dx.doi.org/10.1016/j.medcli.2016.10.034 ∗ Corresponding author. E-mail address: [email protected] (N. Uribe-Etxebarria Lugariza-Aresti).
The detection of the sentinel node, defined as the initial lymph node drainage node from the tumor,1 has become a standard technique in the action guides for breast cancer and melanoma,2,3 improving the accuracy of extension diagnosis and influencing in the choice of later treatments.
˜ S.L.U. All rights reserved. 2387-0206/© 2016 Elsevier Espana,
MEDCLE-3842; No. of Pages 3
G Model 2
ARTICLE IN PRESS N. Uribe-Etxebarria Lugariza-Aresti et al. / Med Clin (Barc). 2017;xxx(xx):xxx–xxx
Mediastinal lymphadenectomy is a standard of low morbidity to increase the accuracy of extension diagnosis. However, infrastaging, which may be up to 20% in stages I, suggests that sentinel lymph node detection techniques in non-small cell lung cancer (NSCLC)4 may be useful. This prospective cohort study was conducted with the hypothesis that it is feasible to detect the sentinel node in the resectable NSCLC using the injection of technetium 99 colloid sulfate at the intraoperative time, and that would provide improvements in tumor staging, with its corresponding influence in therapeutic programs and prognostic boundaries.
Pathological examination It was performed on a deferred basis. Lymph nodes were initially examined with conventional sections using hematoxylin-eosin stains. If these studies were tumor-negative, additional studies were performed on sentinel lymph nodes using serial cuts with intervals of 30 m and IHC with cytokeratin antibodies CK7 and CK20 and TTF1. IHC was considered positive if cell accumulation or individual positive cells were demonstrated with an appropriate cell morphology compatible with tumor cells.
Results Patients and methods Approved by the Research Committee and the Ethics Committee of Cruces Hospital, the study followed the ethical principles of the Helsinki Declaration (as amended at the 59th Seoul General Assembly). People included were informed about the characteristics and the technique of the study, authorizing the same through informed consent prior to the procedure.
Patient selection 52 patients with suspected NSCLC in stage i-iiA or clinical i-iiB (T1-T2, N0 or N1, preoperative M0) were included according to TNM7. Thirty-two patients had a preoperative pathological diagnosis of NSCLC; in 18 patients without preoperative diagnosis, NSCLC was confirmed by intraoperative tumor biopsy performed after radionuclide injection. Four patients were excluded: in 2 the technique could not be performed since the tumor was very central and it did not allow to complete the puncture in its 4 quadrants. In another 2 patients the diagnosis of NSCLC was ruled out. However, in these cases there was also evidence of radionuclide migration. Therefore, 48 patients were included in the study: 41 males (85.41%) and 7 females (14.58%). The mean age of the series was 64.60 ± 7.97 years, with an age range of 43–80 years. According to TNM7, the preoperative stage of the patients was: 20 cases in stage IA (8 T1aN0M0; 12 T1bN0M0), 23 in stage IB (T2aN0M0), 4 in stage IIA (2 T1aN1M0, one T1bN1M0, one T2aN1M0) and one in stage IIIA (T3N1M0).
Sentinel node detection technique
The radioisotope migrated in all 48 cases. In 44 patients, a single sentinel node was located and in 4 patients, 2 were located, 52 sentinel lymph nodes in total. Sentinel lymph nodes were located primarily near the tumor. 61.53% were intercisural and 34.61% were hilar. 3.84% were mediastinal. In 2 patients (4.17%) the first lymph node drainage station was in mediastinal ganglia (skip phenomenon), stations 5 and 6, in 2 tumors of the upper left lobe. The histology of the resected tumors was: 28 adenocarcinomas (3 bronchioalveolar), 15 epidermoids, 2 adenosquamous, 1 undifferentiated and 2 carcinoids. When comparing preoperative and postsurgical N stage (see Table 1), 9 patients increased their stage: 5 patients from stage N0 to N1, 2 patients from N0 to N2 and 2 patients from N1 to N2. Two patients decreased their stage: from N1 to N0. Histological studies revealed metastatic dissemination in 16 of the 52 sentinel lymph nodes examined (30.76%): 8 in intercisional sentinel nodes and 8 in hilar sentinel nodes. In 9 patients (18.75%) the only adenopathy presenting with metastasis was the sentinel node. With the use of IHQ techniques, 2 micrometastases (one hilar and one intercisural) were detected, which were not diagnosed by routine anatomic pathology. Therefore, 2 patients (6.45% of the N0 patients) were staged again as N1. There were no complications related to the sentinel node technique or mortality in the series. The sensitivity of the test was 88.24% (false negative rate 11.76%) and accuracy was 95.83%, with a negative predictive value of 93.94%. Overall survival at 5 years is 56.25%. It is detailed by stages in Table 2.
Table 1 Preoperative-postsurgical stage. Preoperative
For each of the cases, a dose of technetium 99 colloid sulphate of 9.25 MBq divided into 4 syringes of 1 ml was prepared under sterile techniques. The radioisotope was injected at the periphery of the 4 quadrants of the tumor. The minimum time for migration of injected technetium to the lymph nodes was 10 min. The readings were performed with a manual gamma radiation counter with a sterile plastic cover on the reader. Two readings were obtained: in vivo (without drying the piece) and ex vivo (once the piece was resected). Standardized tumor resection was performed together with the resection of the visible mediastinal, peribronchial and hilar lymph nodes. Subsequently, the ex vivo measurement was performed. All those that had a radioactivity 3 times greater than the baseline value of the patient were considered as sentinel lymph nodes. After standard anatomical resection and nodal mediastinal dissection, the thoracic cavity was again inspected with the gamma meter to verify that there was no residual radiation or nodes not detected previously.
Postoperative
T1aN0M0
8
T1bN0M0
12
T1aN1M0
2
T1bN1M0 T2aN0M0
1 23
T2aN1M0 T3N1M0
1 1
T1aN0M0 T1bN0M0 T1bN1M0 T2aN0M0 T2bN1M0 T1aN0M0 T2aN0M0 T2aN1M0 T3N0M0 T1aN1M0 T2aN2M0 T1bN0M0 T1aN1M0 T2aN0M0 T2bN0M0 T2aN1M0 T2aN2M0 T3N0M0 T4N2M0 T2aN0M0 T4N2M0
2 1 2 2 1 1 8 1 2 1 1 1 1 10 2 5 3 1 1 1 1
G Model
ARTICLE IN PRESS N. Uribe-Etxebarria Lugariza-Aresti et al. / Med Clin (Barc). 2017;xxx(xx):xxx–xxx
Table 2 Survival by stages. IA
80%
IB IIA
71.42%
IIB
41.66%
IIIA IIIB
0% 0%
T1aN0M0 T1bN0M0 T2aN0M0 T2bN0M0 T1aN1M0 T1bN1M0 T2aN1M0 T2bN1M0 T3N0M0 T2aN2M0 T4N2M0
66.66% 100% 71.42% 50% 50% 50% 33.33% 0% 100% 0% 0%
Discussion The detection of sentinel node in NSCLC with intraoperative injection of isotopes is feasible and safe.5 In the published series, high test accuracy is appreciated, with a sensitivity of more than 80% for the use of isotope or isotope plus dye, and it does not appear to be a complicated technique to learn and apply.6 However, a multicenter phase II trial did not achieve its selection goal, with a very low sensitivity, apparently due to logistical problems.7 This prospective cohort study is a validation analysis of the technique of sentinel node detection in NSCLC by injection of technetium 99 sulphate colloid, in which it is seen as a feasible, safe and relatively simple technique. Our results, in line with those of other series, with similar precision and sensitivity, point in favor of studying the sentinel node in operable lung cancer. It seems to us to be especially important the greater accuracy in staging (detection of micrometastasis) and the detection of skip-mediastinal metastasis that may have importance in the treatment and prognosis of the patients. We detected the presence of skip metastasis in a smaller amount than in other series, where it was reached up to 33%, probably due to the characteristics of the patients included. Due to legal limitations with the use of isotopes, in Japan they studied the injection of the isotope in a preoperative peritumoral rather than intraoperative manner, with very similar results.8 Intratumoral injection, on the other hand, seems inferior when establishing lymphatic drainage from the diseased area. Some groups have used radiopaque films to remove noise from the injected area but in general, in vivo and ex vivo detection allows localization of drainage nodes from the primary tumor.
3
The use of technetium 99 with or without dye is the most established technique. In the near future it is expected to include novelties, such as magnetic materials,9 fluorescent dyes,10 TAC contrast agents and carbon nanoparticles. In conclusion, the techniques of detection of sentinel node in lung cancer with technetium 99 allow detection rates and a sensitivity superimposable to those of other types of tumor. Conflict of interests The authors declare that they have no conflict of interest. References 1. Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA, Storm FK, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127:392–9. 2. Gershenwald JE, Thompson W, Mansfield PF, Lee JE, Colome MI, Tseng CH, et al. Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage i or ii melanoma patients. J Clin Oncol. 1999;17:976–83. 3. Veronesi U, Paganelli G, Viale G, Galimberti V, Luini A, Zurrida S, et al. Sentinel lymph node biopsy and axillary dissection in breast cancer: results in a large series. J Natl Cancer Inst. 1999;91:368–73. 4. Kubuschock B, Passlick B, Izbicki JR, Thetter O, Pantel K. Disseminated tumor cells in lymph nodes as a determinant for survival in surgically resected non-small cell lung cancer. J Clin Oncol. 1999;17:19–24. 5. Liptay MJ, Grondin S, Fry WA, Pozdol C, Carson D, Knop C, et al. Intraoperative sentinel lymph node mapping in non-small cell lung cancer improves detection of micrometastasis. J Clin Oncol. 2002;20: 1984–8. 6. Taghizadeh Kermani A, Bagheri R, Tehranian S, Shojaee P, Sadeghi R, Krag DN. Accuracy of sentinel node biopsy in the staging of non-small cell lung carcinomas: systematic review and meta-analysis of the literature. Lung Cancer. 2013;80:5–14. 7. Liptay MJ, D’amico TA, Nwogu C, Demmy TL, Wang XF, Gu L, et al. Intraoperative sentinel node mapping with technitium-99 in lung cancer: results of CALGB 140203 multicenter phase ii trial. J Thorac Oncol. 2009;4: 198–202. 8. Nomori H, Horio H, Naruke T, Orikasa H, Yamazaki K, Suemasu K. Use of technetium-99 m tin colloid for sentinel lymph node identification in non-small cell lung cancer. J Thorac Cardiovasc Surg. 2002;124:486–92. 9. Minamiya Y, Ito M, Katayose Y, Saito H, Imai K, Sato Y, et al. Intraoperative sentinel lymph node mapping using a new sterilizable magnetometer in patients with nonsmall cell lung cancer. Ann Thorac Surg. 2006;81:327–30. 10. Yamashita S, Tokuishi K, Miyawaki M, Anami K, Moroga T, Takeno S, et al. Sentinel node navigation surgery by thoracoscopic fluorescence imaging system and molecular examination in non-small cell lung cancer. Ann Surg Oncol. 2012;19:728–33.