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Eur J Cardiothorac Surg 1999;16:619-623
© 1999 Elsevier Science NL

Mesothelioma – VATS biopsy and lung mobilization improves diagnosis and palliation

Department of Cardiothoracic Surgery, Papworth Hospital, Papworth Everard, Cambridge CB3 8RE, UK

Corresponding author. Tel.: +44-1480-830-541; fax: +44-1480-831-315

	Abstract

Top Abstract 1. Introduction 2. Patients and methods 3. Operative procedure and... 4. Results 5. Discussion Appendix A References

 
Objectives: Mesothelioma is an increasingly frequent malignancy in which diagnosis is often delayed and disease diagnosed at an advanced stage. Earlier diagnosis and therapeutic intervention that can control recurrent pleural effusion may improve outlook and survival. Methods: A prospective series of 25 patients in whom mesothelioma was suspected was referred for histological diagnosis by video assisted-thoracoscopy (VAT) after failure of other methods. At the same operative procedure drainage of pleural effusion, cytoreductive pleurectomy and lung mobilization was performed where possible. Complete follow-up was obtained. Results: All patients had a histological diagnosis (100%) from the material sent for biopsy. In 23 patients this was mesothelioma, in two patients chronic empyema. All patients undergoing drainage of effusion, cytoreductive pleurectomy and lung mobilization subsequently were diagnosed of having mesothelioma stages III to IV. Fifteen out of 21 who underwent lung mobilization had closure of the pleural space. Post operative air leak in this group was a mean of 5 days (2–12 days). Recurrent effusion occurred in only one patient. Eleven patients remain alive at 1–2 years post operation with no hospital admissions for recurrent pleural effusion. In the six out of 21 who did not have closure of the pleural space, one remained alive 9 months post surgery. Five died within 1–6 months of the procedure. The average number of further hospital admissions for repeat drainage of effusion was 3 (1–6). Conclusions: VATs provides adequate tissue for histological diagnosis where other methods fail. At the same operative sitting it provides a therapeutic intervention that allows drainage of effusion cytoreductive pleurectomy and lung mobilization in a significant number of cases. Where the pleural space can be closed this results in significantly fewer hospital admissions and appears to improve quality of life and length of survival. The price is a longer hospital stay due to prolonged air leak.

Key Words: Video-assisted thoroscopy • Tumour volume reduction • Pleural space obliteration

	1. Introduction

Top Abstract 1. Introduction 2. Patients and methods 3. Operative procedure and... 4. Results 5. Discussion Appendix A References

 
Our understanding of the natural history and progression of mesothelioma has increased as the reported incidence of the disease rises. It is a cancer likely to be increasingly common well into the next century for which there is currently no standard treatment [1] and in which it is notoriously difficult to promptly and accurately obtain histological diagnosis [2]. Prognosis depends on several factors, the most favourable outcome being associated with epithelial cell type [3]. Overall outcome remains poor largely because presentation is late and diagnosis is difficult but also because treatment options are limited and so far have failed to demonstrate significant improvement in survival. However, multimodality strategies seem promising and include the latest gene transfer technologies [4]. Cytoreductive pleurectomy by debulking tumour load and in association with adjuvant therapy have been associated with longer survival [5,6].

Significant problems remain with obtaining sufficient tissue to make an accurate histological diagnosis and in palliation of recurrent pleural effusion in patients with advanced disease. The evolution of video-assisted thoracoscopy surgery (VATs) has proved to be a useful tool which can provide both these options in one surgical episode, offering a less invasive but as effective procedure as thoracotomy [7]. This approach to the modern treatment of empyaema has shown significant promise in both aiding diagnosis and achieving decortication [8]. We have applied a similar technique of decortication to achieve cytoreduction and lung mobilization in a series of patients referred with a suspected but unproven diagnosis of mesothelioma. We report on our diagnostic accuracy, surgical techniques and patient outcomes in a series of patients with advanced disease.

	2. Patients and methods

Top Abstract 1. Introduction 2. Patients and methods 3. Operative procedure and... 4. Results 5. Discussion Appendix A References

 
Twenty-five patients (24 male, one female, mean age 64 years, range 34–75 years) were referred for further assessment in whom mesothelioma was suspected on clinical and radiological grounds. All had a history of exposure to asbestos with associated symptoms of cough, dyspnoea and/or chest wall pain. Each had abnormally thickened pleura on computerized axial tomography (CT). Those with pleural effusion (n=19) had already undergone pleural fluid tap and pleural biopsy; those with thickened pleura only (n=6) had undergone guided needle biopsy under ultrasound or CT control. In all cases the diagnostic material available from cytology or histology was insufficient to make an unequivocal diagnosis. Where necessary, CT was performed preoperatively to guide the operative procedure for which all patients provided informed consent. Data pertaining to duration of air leak, morbidity and outcome were obtained prospectively and all patients followed up by outpatient review or until death.

	3. Operative procedure and techniques

Top Abstract 1. Introduction 2. Patients and methods 3. Operative procedure and... 4. Results 5. Discussion Appendix A References

 
Endotracheal intubation with double lumen tube is a standard. The minimum number of port access sites is aimed at with CT guidance and was usually two and never more than three. The first port site is positioned over the pleural effusion site at the thinnest point of the parietal pleura, i.e. the most open space facing the effusion. We prefer initial digital exploration of the incision as this provides information on the thickness and rigidity of the parietal pleura and assists in the breakdown of adhesions around the port site thus facilitating visualization. The effusion is drained at this point and the thoracic cavity inspected. Siting of the next port site is determined by these findings to allow access of instruments from apex to base and so that each port site can be utilized to visualize the other. Sponge holding forceps and endodissectors are our instruments of choice to break down any loculi or dissect further adhesions (Fig. 1) The lung surface is then assessed by instrumentation and by asking the anaesthetist to gently reinflate the lung. This gives an immediate indication whether the lung or part of lung is capable of re-expansion. When some parts of lung re-expand and others do not, we attempt further instrumentation to divide adhesions and mobilize fissures. Where no re-expansion occurs, sufficient material is obtained for biopsy of lung and pleural and the portsites closed. Visualization alone can be misleading as an apparently thick callosity of tumour on the visceral surface can be largely fibrinous. Using sponge holding forceps and endo dissectors with repeated episodes of re-inflation, we attempt to mobilize the lung by dividing adhesions around the apex, between the fissures and postero laterally (Fig. 2). We do not attempt to divide diaphragmatic adhesions as the tumour is usually dense at this point. Our technique is similar to that performed in thoracotomy for empyema. In addition, further expansion of the lung can be achieved by superficial incisions in the visceral pleura performed by scalpel in a criss-cross fashion.

View larger version (130K): [in this window] [in a new window]   Fig. 1. Right chest cavity indicating extensive parietal mesothelioma with lung encasement and the beginning of lung mobilization.

View larger version (98K): [in this window] [in a new window]   Fig. 2. Viceral and parietal cytoreduction utilizing simple sponge holding forceps.

View larger version (101K): [in this window] [in a new window]   Fig. 3. Extended parietal decortation of tumour. (b) Completion of parietal decortation and removal of tumour through port access site.

View larger version (131K): [in this window] [in a new window]   Fig. 4. Completed cytoreductive pleurectomy and lung mobilization. Note the cleared plane and reappaearance of chest wall structures.

Once the drains are removed, repeat chest X-ray confirms the extent of pleural space closure. Patients are then referred for radiotherapy to port access sites within 1 month of surgery.

	4. Results

Top Abstract 1. Introduction 2. Patients and methods 3. Operative procedure and... 4. Results 5. Discussion Appendix A References

 
A successful histological diagnosis was made in all patients without mortality. In 23 patients, this was mesothelioma (12 epithelial type, nine mixed morphology and two sarcomatous) and in two, chronic empyema, these two patients undergoing the same procedure with complete resolution. All patients were allocated to stage III or IV (Butchart classification) taking into account, radiological, surgical and histological findings. In two patients, nothing other than biopsy was attainable and they died 2 and 4 months after diagnosis. In the remaining 21 patients, attempts were made using the techniques described to perform lung mobilization, cytoreductive pleurectomy and closure of the pleural space. In 15 patients, extensive cytoreductive pleurectomy was performed and the lung mobilized to successfully close the pleural space. Duration of post operative air leak was 5 days (range 2–21 days). Recurrent pleural effusion occurred in only one patient who died 9 months post procedure. A further 11 remain alive up to 2 years 5 months post procedure with no hospital admissions for recurrent pleural effusion. In the six remaining patients, drainage of the effusion revealed a completely or partially incarcerated lung which made little or no movement after attempts at lung mobilization. This was associated with a parietal pleural thickness greater than 1 cm which extended across the viceral pleura. In this group where the pleural space could not be closed, partial pleurectomy was performed. The duration of post operative air leak was 3 days (range 2–7 days). One patient remains alive 11 months post surgery. Five died within 1–6 months. The number of further hospital admissions for repeated drainage of pleural effusion was 3 per patient (range 1–6).

	5. Discussion

Top Abstract 1. Introduction 2. Patients and methods 3. Operative procedure and... 4. Results 5. Discussion Appendix A References

 
In this prospective study, patients with a suspected but unproven diagnosis of mesothelioma, were referred for diagnostic biopsy and therapeutic intervention. We have demonstrated that VAT techniques have been 100% effective in obtaining a diagnosis with no mortality. At the same operative session, we have utilized cytoreductive pleurectomy and lung mobilization to palliate pleural effusion in a large number of patients who appear to survive longer and do not return to hospital for recurrent effusion. The early price for this is longer duration of air leak in the peri operative period.

It is vital to obtain a prompt and accurate histological diagnosis in patients suspected of having mesothelioma [9]. In this study, we excluded two patients with suspected mesothelioma whose histology indicated chronic empyema. Pleural fluid cytology is only accurate in up to 30% of cases and as in other studies, blind pleural biopsy was unreliable in the group referred to us. New diagnostic schedules utilizing ultrasound and CT guided biopsies are showing promise [2] but do not match the specificity and sensitivity of VATs guided biopsy as demonstrated in this study.

The pleural effusion which causes shortness of breath, cough and chest wall pain and which is the dominant cause of the patient feeling ill, restricts the quality of life in this group of patients whose prognosis is usually already poor. Repeated hospital admission for drainage of recurrent effusion further reduces quality of life in this patient group. Both pleural membranes are usually involved in the exudative effusion resulting from increased capillary permeability due to destroyed capillary endothelium and distorted tumourous lymph drainage [10]. The loss of protein caused by the effusion increases catabolism leading to rapidly developing symptoms. Therapeutic strategies aimed at effective and lasting alleviation of symptoms depend on obliteration of the pleural cavity.

Chemical pleurodesis is a common method with a success rate of up to 30% [11]. The success of pleurodesis depends primarily on closure of the dead space by re-expanded lung where adhesion of the pleural membrane then takes place. If lung re-expansion is not achieved then the likelihood of success is limited.

The complete view of the thoracic cavity afforded by VAT techniques would only otherwise be possible with thoracotomy and it has proved to be a useful tool in diagnosis and therapeutic intervention of many intra thoracic disorders [7,8]. In the treatment of chronic empyema, where the problems of a thick parietal pleura and an incarcerated lung are similar to those of mesothelioma patients, decortication can be achieved in the presence of incarcerated lung with benefits over open thoracotomy [8].

Pleurectomy/decortication has previously been performed in mesothelioma patients to control pleural effusion. In one study this was compared to extra pleural pneumonectomy. Although the treatment intent was different, those who underwent pleurectomy/decortation had all or almost all of their gross tumour removed and although it was a less extensive resection, this group had less perioperative complications and extended survival [12]. Theoretically, cytoreductive pleurectomy, which removes a large proportion of the tumour burden, can make a contribution to improved outcome either by decreasing the protein losing state directly or by release of incarcerated lung and closure of the pleural space and prevention of further effusion and protein loss. In this study, we achieved cytoreductive pleurectomy in a significant number of patients with advanced disease in a group of patients who had similar histological disease. Lung mobilization to release the incarcerated lung was achieved in the same patients with a trend to longer survival compared to the group in whom this was not possible. Improved quality of life as determined by freedom from recurrent pleural effusion was also achieved in this group as compared to those where cytoreductive pleurectomy and lung mobilization was not possible.

Whether this trend is due to reduction of tumour burden directly or by prevention of effusion by closure of the pleural space, was not determined in this study but requires further evaluation. Cytoreductive pleurectomy in this and another study may have a real survival benefit [6,12].

Prospective clinical trials in mesothelioma patients to evaluate our findings and other novel treatment strategies, require an accurate universally accepted and verifiable staging system. Unfortunately, even the new staging system developed by the Mesothelioma Interest Group is not validated [12]. TNM and Butchart stage are not related to survival time, according to the largest study in the UK [13]. This may be related to the inconsistencies applied in the process. Information on lymph node stages may be incomplete or unachievable in many patients as in our study. Advanced stage disease (Butchart III or IV) was accorded to our group from a combination of clinical radiological surgical and histological data in a way similarly ascribed in other studies [12,14]. Over all histological type seems to be the major determinant of survival and was spread evenly in the patients in our study.

In conclusion, we have shown that VATs technique can provide sufficient tissue for histological diagnosis where other methods have failed and at the same operative session, allows therapeutic intervention to palliate pleural effusion. Cytoreductive pleurectomy and lung mobilization which closes the pleural space is associated with longer survival and better quality of life but requires further study to elucidate its direct benefits.

	Footnotes

 
Presented at the 12th Annual Meeting of the European Association for Cardio-thoracic Surgery, Brussels, Belgium, September 20–23, 1998.

	Appendix A

Top Abstract 1. Introduction 2. Patients and methods 3. Operative procedure and... 4. Results 5. Discussion Appendix A References

 
Conference discussion
Dr H. Toomes (Gerlingen, Germany): As you said, you have small series, so it's not so easy to make statements from these small series. Have you used talc in your hospital? It works also very good. We have a very good experience and it's very easy to perform.

Mr M.W.J. Grossebner: Right. We have not used it in these patients. We felt that at VAT we can take away most of the tumor. And as I said, most of these lungs actually came up expanded fully and obliterated the pleural space without using talc or any other substances.

Dr D. Van Raemdonck (Leuven, Belgium): First, can you tell us on average how many ports you are using for this intervention? And secondly, do you send these patients for irradiation of the ports afterwards?

Mr Grossebner: Yes, we usually use two, sometimes three holes. We start with two. But if it's complicated to actually do the extensive pleurectomy, then we sometimes have to introduce a third hole. And yes, the patients all get radiotherapy to the port holes. We had one patient who had a recurrence of the tumor at the actual port site. So they all get radiation to the port sites as well.

Dr Joachim Hasse (Freiburg, Germany):

You showed in your film a case where the mesothelioma was not forming a thick cortex of tumor as it often occurs in this disease. Only then you will be able to persue this procedure. Otherwise you would not. I suppose there was rather little tumor mass in the VATS cases. Was the histological work-up from the parietal pleural specimen or did you take additional biopsies from the lung? Also, did you look for asbestos foreign bodies? As a comment, on the use of talcum, in my experience, this should be restricted to those cases where the lung is fully expandable. If not, one will leave a space, and in the case of infection, it could turn out to be very difficult to treat with the talcum inside.

Mr Grossebner: Indeed, sir, it looked quite easy to take these flaps off, tumor off the chest wall. And we had patients, as I reported, where we were not able to expand the lung and do a procedure as good as in the majority of our cases. So if the tumor is really adherent, it is very complicated, and we were not able to actually expand there. And yes, indeed, the biopsies were sent from different aspects of the pleural cavity and from the lung as well, clearly marked for the pathologist, in order to actually give us a chance to stage as good as possible.

Mr V. Zamvar, (Cardiff, UK): Did you have a problem with excessive blood loss in these patients? And do you ever have to convert it into an open thoracotomy to be able to thoroughly debulk the tumor?

Mr Grossebner: In this group we have not needed an open thoracotomy. And yes, indeed, it is a very bloody procedure. Obviously, you have to sometimes transfuse if there is too much blood loss. But, also, before we actually close, we will have a good look around; and if there is any obvious bleeding, we have so far been able to stop those major bleeds with diathermy in these cases. But we did not have to convert to open procedure in this group of patients.

	References

Top Abstract 1. Introduction 2. Patients and methods 3. Operative procedure and... 4. Results 5. Discussion Appendix A References

 

1. Chahinian A.P. Therapeutic modalities in malignant pleural mesothelioma. In: Chretien J., Hirsch A., eds. Diseases of the pleura. New York: Masson, 1983:224-236.
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3. Boutin C, Rey F, Gouvernet J. Malignant mesothelioma: prognostic factors in a series of 125 patients studied from 1973 to 1987. Bulletin de l’Academie Nationale de Medecine. 1992;176(1):105-114 (discussion 115–117).
4. Kukacs K.V., Steel R.M., Oakley R.E., Pardo O.E., Jeffery P.K., Geddes D.M., Alton E.W.F.W. Towards a clinical trial of HSP65 gene therapy for malignant mesothelioma. Thorax 1998;53(Suppl 4):S80.
5. Rusch V.W., Saltz L., Venkatraman E., et al. A phase II trial of pleurectomy/decortation followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma. J Clin Oncol 1994;12:1156-1563.[Abstract/Free Full Text]
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11. Furrer M., Inderbitzi R. Fallbericht: endoskopische resektion eines 5 cm grossen intra thorakalen lipoms. Pneumonalogie 1992:46.
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