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ORIGINAL ARTICLES |
From Oncologic Thoracic Surgery (PPBM, CL, IC), Istituto Nazionale Tumori, Milan, Italy; Statistical Unit (BM), Istituzioni Assistenziali Riunite (IIAARR), Pavia, Italy; General Surgery (FF), Ospedale Civile, Voghera (PV), Italy.
Correspondence: Address correspondence and reprints requests to: Pier Paolo Brega Massone, MD, Via Cascina Spelta 24/b, 27100 Pavia, Italy; Fax: 39-022-360486; E-mail: ppbm{at}virgilio.it
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSCONCLUSIONSREFERENCES |
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Methods: In our Institute, from 1995 to 2001, 85 patients underwent VATS biopsy: 55 subjects (group 1) for suspected lung cancer (65%) and 30 (group 2) for unknown nodes enlargement (35%). Lymphonodes were considered suspected if > 1 cm by radiological imaging. We performed 83 thoracoscopic biopsies: 33 in level 5 (39%), 24 in level 6 (29%), 19 in level 7 (22%), and 7 in level 8 (8%).
Results: A histological analysis of frozen sections was made in every case. Twenty subjects underwent lung resection in one-time (24%). Histology in group 1 was adenocarcinoma in 28 cases, epidermoid carcinoma in 14, microcytoma in 9, and giant-cell carcinoma in 4. Ten patients were at stage I, 10 at stage II, 33 at stage III, and two at stage IV. Histology of group 2 was lymphoma in 18 cases, sarcoidosis in eight, and focal aspecific hyperplasia in four.
Conclusion: The usefulness of VATS allowed the pathological assessment of the presumed involved mediastinal lymph nodes in every patient and thus permitted to assure in all the cases the indicated therapeutic treatment.
Key Words: Mediastinal lymph nodes • Video-assisted thoracoscopic surgery • Diagnostic biopsies • Therapy
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSCONCLUSIONSREFERENCES |
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The main causes of mediastinal node enlargement are benign diseases (such as sarcoidosis and tuberculosis) and malignant tumors, the most frequent of which are lung carcinomas. A precise staging of the mediastinum is essential when choosing the most appropriate treatment for patients with lung cancer, because the lymph node invasion and the degree of infiltration are factors conditioning the choice of therapy (surgery vs. neoadjuvant treatment vs. definitive chemotherapy).
A large number of surgical techniques for the exploration of the mediastinum have been described in the past.1–4 Video-assisted thoracoscopic surgery (VATS) has been successfully used to perform biopsies in those lymph nodal stations that seem to be more difficulty reaching by other procedures, such as the subaortic (aortopulmonary window) nodes (level 5), paraaortic (ascending aorta or phrenic, level 6), subcarinal (level 7), paraesophageal (below carina, level 8), and pulmonary ligament (level 9).5
Nowadays, a real standard technique for the assessment of mediastinal lymph nodes enlargement of unknown origin has not yet been defined, and even if the advantages of a procedure versus another seem to be clear, the use of one of these surgical methods must be chosen in accordance with the right indications and the personal experience.
The aim of our work is to evaluate the use, the safety, and the versatility of VATS to perform diagnosis of lymphadenopathies of the mediastinum.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSCONCLUSIONSREFERENCES |
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Between January 1995 and September 2001, 85 patients with mediastinal lymph node enlargement underwent VATS biopsy: 47 males (55%) and 38 females (45%), with a mean age of 55.85 ± 9.73 years (median, 54; range, 25–78).
The patients were divided into two groups: group 1 consisted of 55 patients with suspected primary lung cancer (65%) and group 2 of 30 subjects (35%) with mediastinal lymph node enlargement in the absence of any other clinical sign.
The biopsies of the patients in group 1 were performed for staging purposes in order to allow us to decide how to continue the treatment, the operation was stopped in the case of neoplastic mediastinal involvement, the other cases immediately underwent thoracotomy; the biopsies of the patients in group 2, in whom the presence of disease was only suspected on the basis of clinical presentation and radiological imaging, were performed in order to obtain a histological diagnosis and decide the most appropriate therapy.
A lymph node > 1 cm was considered suspect at computed tomography (CT) evaluation. In the last 3 years, we also associated whole-body positron emission tomography (PET), and we considered for surgical biopsies patients with lymph nodal positive captation.
VATS biopsies have to be necessarily performed under general anesthesia because the ipsilateral lung must be collapsed and needs mechanical ventilation support. In order to acquire a complete view of the thorax cavity and to facilitate all of the surgical procedures, the patients were submitted to one-lung selective ventilation by orotracheal intubation utilizing a double-lumen Carlens tube.
They were placed in lateral decubitus, as we do in case of posterolateral thoracotomy, and the first thoracoport, used for videothoracoscope introduction, was positioned in the VI or VII intercostal space on the middle axillary line; the other accesses, in the majority of the cases two, were placed under the direct vision of the thoracoscope on the anterior and posterior axillary lines. We first explored the thorax cavity and, in the case of adhesions, executed pleurolysis; we successively opened the mediastinal pleura in order to look at the lymph node stations and then performed the biopsy.
This technique permits a panoramic exploration of the homolateral hemithorax: in the left hemithorax, we visualize the paraaortic and the subaortic levels. In both hemithoraces, it is possible to biopsy the subcarinal lymph nodes, the paraesophageal, and pulmonary ligament nodes. Suspected disease of lymph nodal stations 5 (Fig. 1), 6, 7 (Fig. 2), 8, and 9 were indicated for a surgical minimal invasive biopsy.
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In case of positive histological test at the frozen section for neoplastic disease, the operation was stopped in patients of both groups. In case of subjects affected by lung cancer, the negative histological examination at the frozen section determined the prosecution of intervention through a thoracotomic access.
The unknown lymph node enlargement was on the left side in 62 cases (73%), and on the right in 23 (27%).
Lymphadenopathy biopsies were performed in 83 cases (98%): 33 at level 5 (39%), 24 at level 6 (29%), 19 at level 7 (22%), and 7 at level 8 (8%).
In two patients with mediastinal lymphadenopathies enrolled in this study (2%), we occasionally found a pleural micronodulation that were not suspected preoperatively. Therefore, we obtained the diagnosis by means of pleural biopsy.
The lymph node enlargement in the 55 patients with suspected lung cancer who underwent diagnostic VATS was ipsilateral in 46 cases (54%) and contralateral in 9 (11%).
The details of the specimens taken from the two groups are given in Table 1.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSCONCLUSIONSREFERENCES |
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The patients with primary lung cancer, whose lymph node specimens showed no evidence of neoplastic cells at the analysis of frozen sections, were submitted to one-time lateral thoracotomy for lung lobar resection. Twenty one-time operations were executed: 16 lobectomies, 1 bilobectomy, and 3 pneumonectomies. All of these patients underwent hilar and mediastinal lymphadenectomy in order to allow precise postoperative staging.
When the histological analysis of frozen sections revealed the presence of inflammatory disease, we waited for the definitive histology before starting specific medical treatment. Analyzing the VATS diagnostic procedure results, we had no perioperative mortality or postoperative morbidity.
Postoperative pain in the 63 patients who underwent only VATS lymph node biopsy (74%) was lower than in the patients who underwent to minimal lateral thoracotomy for the same reason in a previous experience.
We consider as parameters to evaluate postoperative pain the kind and the quantity of analgesics used in the first 3 postoperative days, referring to the World Health Organization (WHO) three-step scale.6 The first step implies the utilization of nonsteroid antiinflammatory drugs for mild or moderate pain. The second step implies the use of opioid drugs for increasing pain (from moderate to severe) nonresponsive to nonsteroid antiinflammatory drugs. The third step refers to severe noncontrolled pain that needs only opioids and/or adjuvant analgesics subministration. All VATS-treated patients were at step 1, and we used only nonsteroid antiinflammatory drugs such as ketorolac tromethamine, whereas 70% of the subjects submitted to thoracotomy were at step 2 and needed opioids.
The mean operating time, the average thoracic drain duration, and the mean hospital stay of patients submitted to lymph nodal biopsy by means of video-assisted thoracic surgery are reported on Table 2. Histology of group 1 and 2 patients is resumed on Table 3.
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At the time of definitive diagnosis, patients affected by bronchogenic tumor were submitted, as general indications, to neoadjuvant therapy in presence of N2 disease, whereas a definitive treatment was proposed for subjects with N3 disease and for those with distant metastases.
Of the group 1 subjects who underwent VATS biopsy, according to the Mountain revision7 of the International System for Staging Lung Cancer, 24 were classified at IIIA (28%) and 9 at stage IIIB (11%), whereas the two subjects who underwent pleural biopsies were at stage IV (2%). Among the 20 patients who underwent one-time lung resection, 10 were at stage I (12%) and 10 at stage II (12%).
Nineteen patients with stage IIIA non-small-cell lung cancer (NSCLC) received neoadjuvant chemotherapy. Eight of these subjects underwent surgical resection after preoperative treatment (42% of all treated patients). Five patients affected by NSCLC and classified at stage IIIB were submitted to definitive chemotherapy and mediastinal radiotherapy. Nine subjects with small cell lung cancer (SCLC) at stage IIIA and IIIB received chemotherapy in association with radiotherapy, and preventive panencephalic radiotherapy. One of the two subjects at stage IV was treated with definitive chemotherapy, whereas the other received only symptomatic therapy.
The group 2 patients affected by specific or oncological disease were given appropriate therapy. Eighteen patients with lymphoma underwent integrated chemotherapy and radiotherapy, and 8 subjects with sarcoidosis received specific medical treatment.
The impact of VATS experience in cases of mediastinal lymph nodal enlargement on pathological diagnosis and successive therapy is summarized on Table 4.
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In this study, we report our experience of VATS as a diagnostic technique for mediastinal lymph node enlargement and its usefulness on the selection of the successive optimal therapy.
In fact, in the case of chance radiological findings without any symptoms, the aim of biopsy is to make a rapid histological diagnosis in order to be able to start the most appropriate treatment; however, a large number of such patients have symptoms, particularly dysphagia, pain, and cough. The most important neoplastic diseases with a mediastinal lymph node localization are lymphomas and germ cell tumors, which require the administration of chemotherapy as soon as possible. These tumors sometimes appear as very large mediastinal masses that can be biopsied by means of TC-guided fine-needle aspiration, which can be performed under local anesthesia, has a diagnostic sensitivity of about 70%, and is associated with a low incidence of complications (1%). However, agobiopsy has a number of limitations11,12: in the case of lymphomas, the majority of specimens are not enough to allow an accurate diagnosis or the identification of particular cell patterns. In our opinion, this procedure cannot be considered an alternative to VATS, but may be complementary.
With the development and refinement of guidance modalities for percutaneous biopsies, percutaneous core-needle biopsy (by means of tru-cut) has been proposed to obtain adequate biopsy samples to perform a correct diagnosis and classification of lymphoma. This technique described to have a sensitivity of 81%–89% is appropriate for anterior mediastinal masses or enlarged lymph nodes and seems to be a first less invasive alternative to mediastinoscopy.13
Mediastinoscopy is still the most widely used mediastinal lymph node bioptic procedure for lung cancer.14 It allows the visualization of the pretracheal space, extraluminal trachea, mainstem bronchi, and mediastinal lymph nodes, but its indications are for paratracheal nodes and a partial anterior approach for subcarinal lymph nodes (levels 2R, 4R, 2L, 4L, anterior 7 R/L).9
The indication of mediastinoscopy continues to evolve, and authors have extended this diagnostic procedure to patients without clinical lymph nodal involvement to identify a subgroup of subjects with radiologically occult nodes metastases.15
Access to the aorticopulmonary window may be difficult and is limited by the aorta and left mainstem bronchus. The diagnostic sensitivity of mediastinoscopy is 65%–90%, and the complications rate is 1%–3%.2,16
For level 5 and 6 lymphadenopathies, it may be easier to perform anterior or parasternal mediastinotomy but, although its diagnostic accuracy is good, this procedure is not widely used and some complications may occur.17 A transpleural access has been proposed, but if this approach offers a wider view on the left side, it increases very much the invasiveness of this technique without a related advantages such in VATS procedure.18
Less invasive techniques used in the last period are transesophageal endoscopic ultrasonography–guided fine needle aspiration (EUS FNA) and transbronchial fine-needle aspiration executed by means of bronchoscopy.19 These are presently specific for subcarinal lymph nodes biopsy, and they are useful procedures in experienced hands; however, the experience in our Institute is yet limited.
Open biopsies by minithoracotomy are now decreased after VATS advent for the reduction of surgical trauma and postoperative pain. Minimal invasive surgical procedure, associated with modern anesthetic techniques, has made it possible to operate on patients who were previously considered to be at too high risk for open thoracotomy.20 Focus on mediastinal masses, the open procedure is today limited to the possibility of removing tumor radically.21
VATS has changed the indications for all of the above techniques, particularly in relation to the diagnosis of mediastinal enlargement, and in presence of lung cancer permits to complete locoregional staging, but we can add that it can also be used to take tissue samples for histological examination in order to allow an intraoperative evaluation useful for preoperative staging.
Moreover, VATS makes it possible to reach all lymph node stations, including the posterior subcarinal, paraesophageal, and prevertebral stations. As reported in the literature, once sufficient experience has been acquired, it is also possible to execute a systematic complete lymphonodal dissection.22
Nowadays in cases of mediastinal lymph nodal enlargement, mediastinoscopy and VATS are considered the choice treatments for the obtaining of diagnosis. These two procedures are complementary and not alternative procedures, and one integrates the other, allowing to biopsy all the lymphonodal stations of the mediastinum. In fact, the lymphadenopathies level gives the indication to the technique to prefer.
In the Oncologic Thoracic Surgery of National Cancer Institute of Milan, mediastinoscopy is used for bilateral or ipsilateral superior mediastinal lymphonodes enlargement (levels 2R, 4R, 2L, and 4L) when these lymph nodes are the only disease site or in presence of a nonresectable neoplasm (diagnostic procedure) or for excluding a suspected lymph nodal involvement in case of a resectable neoplasm (prethoracotomic step).
We generally utilize video-assisted thoracoscopic surgery in the other cases (levels 5, 6, 7-8-9 R/L). This approach has led to a decrease in the number of anterior mediastinotomies, which are now limited to selected cases in which an intrapleural evaluation of neoplasm is not required. As a matter of fact, mediastinotomy and mediastinoscopy allow adequate specimens to be obtained for histological diagnosis, but do not provide a complete view of the mediastinum and thorax cavity in the presence of large mediastinal masses or lymphadenopathies, whereas VATS allows a complete direct view that makes it possible to evaluate possible radical surgery.
Mediastinoscopy on the contrary allows a bilateral exploration versus the ipsilaterality of VATS. We have always used the lateral approach, and we have no experience with the anterolateral approach described by Sugarbaker.23
VATS permitted to define precise diagnosis in all our cases, to enable an accurate staging, and thus to select the optimal therapy.
We excluded the neoplastic involvement of N2 stations in 20 patients performing lateral thoracotomy for one-time lung cancer resection. Stage IIIA patients started with a neoadjuvant treatment and subsequently underwent restaging to establish the new therapeutic step: rescue to surgery versus complementary radiotherapy. The inoperable stage IIIB patients started integrated chemotherapy and radiotherapy. SCLC patients underwent integrated chemotherapy and radiotherapy as well as panencephalic radiotherapy.
We have not had any problems of pathological classifications in case of lymphoma. All the specimens were adequate for a correct diagnosis; all the patients were sent to the Oncology Unit of our Institute and successively underwent to chemotherapy and subsequent radiotherapy as in the current treatment of malignant lymphoma.24
Patients with sarcoidosis diagnosis were treated on the basis of clinical situation according to the pneumological guidelines.25 Subjects with a symptomatic disease and those showing active organ involvement received corticosteroids therapy. In the four cases with aspecific focal hyperplasia, we are able to exclude specific or oncological disease and the patients remained under control for 1 year.
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CONCLUSIONS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSCONCLUSIONSREFERENCES |
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In adjunct to mediastinoscopy, minimal invasive thoracoscopic surgery can be used to stage selected levels of mediastinum lymphonodes in benign and primary malignant disease, or in case of lung cancer, and these two procedures together make it possible to obtain a correct ipsilateral and bilateral lymph nodal map. The real impact on therapy, after the definition of diagnosis, was positive because we are able to select the optimal treatment in every case, establishing with surety all the kind of pathologies determining lymph nodes enlargement.
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ACKNOWLEDGMENTS |
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The study was performed in the Department of Oncologic Thoracic Surgery of Milan National Cancer Institute.
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FOOTNOTES |
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The authors evaluated the effectiveness of video-assisted thoracoscopic surgery (VATS) in the diagnosis and therapy of mediastinal lymphadenopathies. VATS usefulness allowed the pathological assessment of involved nodes in every patient permitting to assure the correct therapy in all the cases.
Received for publication March 7, 2003. Accepted for publication September 3, 2003.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSCONCLUSIONSREFERENCES |
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This article has been cited by other articles:
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  F. C. Detterbeck, M. A. Jantz, M. Wallace, J. Vansteenkiste, and G. A. Silvestri Invasive Mediastinal Staging of Lung Cancer: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition) Chest, September 1, 2007; 132(3_suppl): 202S - 220S. [Abstract] [Full Text] [PDF]
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