The Management of Malignant Pleural Mesothelioma Single Centre Experience in 10 Years

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European Journal of Cardio-thoracic Surgery 22 (2002) 298–305

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The management of malignant pleural mesothelioma;


single centre experience in 10 years q
Tarek Aziz, Ali Jilaihawi, Dhruva Prakash*
Division of Thoracic Surgery, Hairmyres Hospital, East Kilbride, G75 8RG, Scotland, UK

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Received 16 September 2001; received in revised form 31 January 2002; accepted 1 May 2002

Abstract
Background and Objectives: Malignant pleural mesothelioma (MPM) is an asbestos-related disease of the pleura with a survival time
without treatment ranging from 4 to 12 months. The objective of this study is to review our experience in selection of MPM patients for
various modalities of treatment. Methods: Between 1989 and 1998, 302 patients with MPM have been referred to our Centre for assessment.
Majority (191 patients, 61%) of them received no specific treatment. Forty-seven patients were treated by decortication/pleurectomy and 64
had a radical extra-pleural pneumonectomy (EPP). Intrapleural chemotherapy and systemic post-operative chemotherapy was employed only
in the last 51 patients following radical surgery. Results: The average survival was 8.9 months for those treated by palliative care only. The
average survival was 13 and 14 months for patients treated by radical surgery only or by decortication/pleurectomy, respectively. However,
survival has improved to a mean of 35 months for patients treated by radical surgery followed by systemic post-operative chemotherapy. In
this group, the survival prevalence was 90 and 70% for T1 patients and 85 and 36% for T2 patients at 1 and 3 years, respectively (P ¼ 0:002).
Survival was surprisingly, not affected by lymph node involvement (P ¼ 0:08) or pathological type of MPM (P ¼ 0:07). The operative
mortality was 9% for EPP and 0% for decortication/pleurectomy. Conclusion: In selected patients with MPM, complete surgical resection by
EPP represents an important initial step in their management. Systemic chemotherapy improves survival in surgically treated patients.
Further trials are needed to improve on the adjuvant treatment regimes. q 2002 Elsevier Science B.V. All rights reserved.
Keywords: Malignant pleural mesothelioma; Extra-pleural pneumonectomy; Chemotherapy

1. Introduction population in 1996 and nearly 10,000 new patients with


MPM are expected to be diagnosed in the UK during the
Malignant pleural mesothelioma (MPM) is a mesoder- next decade. Therefore, the development of innovative
mally derived neoplastic disease that arises in the pleura treatment strategies should be pursued. In most reports the
and grows relentlessly into adjacent structures (namely the median survival time for patients with this disease without
lungs chest wall and heart), until it ultimately results in the specific treatment is less than 1 year [4]. At the present time,
death of the patient [1]. Asbestos is causally related to the no standard approach exists for the treatment of this disease.
pathogenesis of this malignancy with up to 80% of patients Recommended approaches range from supportive care only,
having a history of asbestos exposure [2]. Although MPM is to single modality therapy (e.g. operation or radiotherapy, or
thought to be a rare neoplasm, approximately 3000 patients chemotherapy) and rarely trimodality therapy [6–8].
continue to be diagnosed with MPM in the United States In the absence of randomised trials, it is not possible to
every year and one should consider that over the next 20 define optimal treatment. This retrospective study looks at
years, 80,000 new cases of mesothelioma MPM are guidelines for selection of MPM patients for appropriate
expected in the United States alone [3]. In Scotland, UK, treatment considering their clinical and radiological status
the incidence of MPM has been continuously rising from at presentation.
2.7/100,000 in the population in 1976 to 8.9/100,000 in the

q
Presented at the joint 15th Annual Meeting of the European Association 2. Patients and methods
for Cardio-thoracic Surgery and the 9th Annual Meeting of the European
Society of Thoracic Surgeons, Lisbon, Portugal, September 16–19, 2001.
* Corresponding author. Tel.: 144-1355-584-661; fax: 144-1355-584- 2.1. Patient assessment
473.
E-mail address: [email protected] (D. Prakash). Between 1989 and 1999, 302 patients were observed at
1010-7940/02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved.
PII: S10 10- 7940(02)0027 3-7
T. Aziz et al. / European Journal of Cardio-thoracic Surgery 22 (2002) 298–305 299

this centre for diagnosis and where appropriate for treatment 3. No co-morbidity preventing major surgery.
of diffuse MPM. Assessment of the patients included clin- 4. Good function in opposite lung.
ical examination, full medical assessment, and computer- 5. No abdominal or distant metastasis.
aided tomography (CAT) scan of chest and abdomen. Pre- 6. Age less than 60 years.
operative tissue sampling of the affected pleura was
obtained by a small open pleural biopsy in all patients.
The pathologic diagnosis was always based on both histol- 2.3. Operative technique
ogy and immunohistochemistry. Pleural fluid cytology, fine EPP was performed as described by Butchart et al. in their
needle and trucut needle biopsies were rarely helpful in our classic paper in Thorax [6]. Briefly, The resected specimen
centre because of false negative and equivocal reports. includes the entire parietal and visceral pleura en bloc with
Magnetic resonance imaging was not used for pre-operative the underlying lung and the ipsilateral pericardium and
assessment in any patient in our series. diaphragm. Blunt dissection is used to separate the
Those who were considered for extra pleural pneumo- diaphragm from the peritoneum underneath, which is left

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nectomy (EPP) underwent further full respiratory function intact. The diaphragm is reconstructed using a prosthetic
testing including ventilation–perfusion scan to assess the patch of two-way stretch Dacron velour sewn circumferen-
potential function of the opposite lung. Computed tomo- tialy at the level of the rib incision. The ipsilateral pericar-
graphic (CT) scans were inadequate to distinguish between dium in contact with the affected pleura is excised dividing
lymph nodes and tumour nodules in the same area, hence the phrenic nerve between ligatures high in the mediastinum
pre-operative staging was not satisfactory. The recently at an early stage. The pericardium is reconstructed using a
developed IMIG staging system was applied retrospectively prosthetic patch of mercilene mesh, inserted loosely like a
to each patient who under-went EPP, to determine his or her hammock to prevent cardiac herniation. We have been using
TN status and corresponding tumour stage (Table 1). Trasylol (Bayer PMO) routinely since January 1993 to prevent
Staging was based on precise information about tumour fibrinolysis and have thus reduced average blood loss by
extent noted at surgery and on node sampling as reported about 1 L in cases since. Two intercostal drains are used,
by the pathologist. one above and the other below the newly constructed
diaphragm, to measure post-operative blood loss accurately.
2.2. Patient selection
2.4. Adjuvant chemotherapy
Patients with extensive disease including chest wall inva-
sion and metstases were only offered best supportive care as The initial 13 patients had a radical resection (EPP) only
were patients who were not fit for major surgery unless they without adjuvant chemotherapy (Group I). Their mean
qualified for a lesser procedure. A lesser procedure such as survival was only slightly better than for those who received
decortication/pleurectomy was considered for locally exten- no definitive treatment. Subsequent 51 patients therefore
sive disease but only for relief of pain or shortness of breath. received chemotherapy post-operatively (Group II). A plati-
The decision to perform an EPP as opposed to a parietal num based combination of Carboplatin and the anthracy-
pleurectomy/decortication was based on the extent of the cline drug Epirubicin was used in all patients in Group II.
tumour and fitness for major surgery. An age limit of 60
years was later used in order to limit operative mortality 2.4.1. Intrapleural chemotherapy
until the benefits of surgery are identified and established. Post-operatively Carboplatin 1 g (Faulding DBL) was
Our criteria for selection of patients with MPM for radical instilled intrapleurally into every patient in Group II before
resection were as follows: chest drain removal.

1. Disease confined to one hemithorax. 2.4.2. Systemic chemotherapy


2. No mediastinal or chest wall invasion. Systemic adjuvant chemotherapy was given to the 51
patients in Group II who underwent EPP after 1992.
Table 1 Depending on how well the patients recovered from the
Staging system of patients after extrapleural pneumonectomy
operation they were given their first treatment about 3–5
Tumour staging Number of patients weeks after operation. The chemotherapy regime consisted
of intravenous bolus of Carboplatin (1 g) followed by an
T1 28
intravenous infusion of Epirubicin (Pharmacia and Upjohn)
T2 30
T3 6 50 mg/m 2/body surface area. The treatment was repeated
N0 25 every 4 weeks for four treatments. Appropriate hydration
N1 22 and antiemetic regimes were used for all patients. Close
N2 17 haematological and biochemical monitoring of the patients
N3 0
was practised and the next chemotherapy course was post-
M 0
poned if nausea, vomiting, or anorexia was present or if
300 T. Aziz et al. / European Journal of Cardio-thoracic Surgery 22 (2002) 298–305

myelosuppression persisted at the time chemotherapy was


next due. However, no dose modification was made.

2.5. Follow-up policy

Patients were followed up regularly as an outpatient at


our institution as long as they lived. Follow-up consisted of
clinical assessment and a chest radiograph with CT scan of
chest annually or as required. Confirmation of suspected
disease recurrence was also documented histologically
whenever possible (80% of the recurrences). If recurrence
was documented, repeating the course of systemic
chemotherapy was considered if the patient was fit. Where
chest wall masses were present, visible shrinking of the

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tumour with the chemotherapy was often noted. In some Fig. 1. Mode of the presenting symptoms for the study population.
cases the symptoms such as ascites and signs of recurrent
disease regressed or were kept under control for the duration no specific treatment other than best supportive (palliative)
of treatment and for 3–6 months thereafter suggesting care. Their median survival was 7 months (1–19 months)
tumour control rather than cure. If the patient was not fit and this group will not be considered here any further.
or active at the time of recurrence, palliative care was
initiated.
3.1.3. Patients undergoing decortication/palliative
2.6. Statistical analysis pleurectomy
Survival time was calculated from the date of the opera- This lesser procedure was employed in 47 (15%) patients
tion (radical EPP, decortication/pleurectomy or open pleural who were reasonably fit but had locally extensive disease.
biopsy for unoperated patients) to the date of death or last The aim of this procedure was to attempt palliation of trou-
follow-up, and survival curves were constructed using blesome symptoms particularly chest pain and pleural effu-
Kaplan–Meier method. The relationships of patient, MPM, sion. This number included three patients who had been
and treatment variables to the outcome of survival and planned to undergo EPP but the operative plans were modi-
recurrence were univariately examined using the two- fied to pleurectomy in view of operative findings (extensive
sided Log rank test. Fisher’s exact test was used to examine mediastinal invasion in three patients). There was no opera-
associations between patient groups and treatment vari- tive mortality in this group. The benefits in terms of relief of
ables. symptoms were not impressive but admittedly difficult to
assess in this small retrospective study.

3. Results
3.1.4. Patients selected for radical surgery
3.1. Patients demography Sixty-four patients were clinically and radiologically in
stage I–II MPM and fulfilled the criteria set out above, and
3.1.1. All study population were treated by extra pleural pneumonectomy. The first 13
Between 1989 and 1999, 302 patients with MPM have patients did not receive systemic chemotherapy (Group I),
been refereed to our institution for assessment. The median while the remaining 51 patients did receive systemic
age was 57 years (range 34–77 years). Sixty-one patients chemotherapy (Group II).
(20%) were females and history of smoking was reported in Pre-operative CAT scan identified pleural thickening in
202 patients. Clear history of asbestos exposure was docu- all patients. Sub-diaphragmatic, chest wall and contralateral
mented in 288 patients and the median duration between pleural involvement was excluded prior to radical surgery.
asbestos exposure and development of MPM was 26 years According to IMIG staging system, 28 patients had T1
(range 19–37 years). The mode of presentation is shown in tumour, 30 patients had T2, and six had T3. Thirty-nine
Fig. 1. patients had nodal metastases of which 25 had only N1
and 14 patients had ipsilateral mediastinal lymph nodes
3.1.2. Patients for best supportive care (N2). None of our study population was proved to have
The majority of patients (191 patients, 63%) had locally N3 or M1 disease. The histological tumour type was epithe-
extensive or metastatic disease at the time of referral to us or lial in 35/64 patients (54%), fibrosarcomatous in 22/64
were in quite poor health. They tolerated an open pleural patients (35%) and mixed cellularity in 7/64 patients
biopsy to establish the diagnosis beyond doubt, thus (11%). Thirty-eight patients underwent right EPP while 26
strengthening their compensation claims. They were offered patients required a left-sided procedure.
T. Aziz et al. / European Journal of Cardio-thoracic Surgery 22 (2002) 298–305 301

3.2. Operative outcome 10/13 patients died within 5 weeks (range 3 weeks to 6
months) following diagnosis of the recurrence.
3.2.1. Mortality
The 30 days operative mortality for EPP patients was 6/
3.3.2. Radical surgery 1 systemic and intrapleural
64 (9.1%). No significant differences in mortality were
chemotherapy
found with regard to patient sex, pre-operative forced
The median time to relapse for patients who received
expiratory volume (FEV1), mediastinal lymph node invol-
chemotherapy following their radical surgery was 37
vement, or pre-operative oxygen saturation. However,
months (14–42 months). There were 31 patients who
survival was inversely affected by patient age and right-
recurred at 33 sites, among the 51 evaluable patients
sided EPP. Five out of six patients died of adult respiratory
(60%). Thirty-two (88%) of the recurrences were confirmed
distress syndrome from 9 to 30 days after operation. One
by histological or cytological assessment [5]. Radiological
patient died of acute myocardial infarction on the third post-
imaging studies and physical examination determined the
operative day and significant coronary artery stenosis was
recurrence in the remaining case. The sites of the first recur-
revealed in his post-mortem examination.

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rence are listed in Table 2. Recurrence was treated by the
There was no operative mortality in the 47 patients who
same regime of systemic intravenous chemotherapy when-
underwent pleurectomy or decortication.
ever patient fitness permitted. Twenty-three of 31 patients
with recurrence received up to six treatments each at
3.2.2. Major post-operative complications following EPP monthly intervals. In six of these patients, the course of
Including the six patients who died, the major morbidity treatment had to be cut short and stopped due to excessive
rate was 14 out of 64 (21%). Major complications included toxicity or disease progression during treatment. The aver-
pulmonary oedema, or adult respiratory distress syndrome age survival of the 17 patients who received a full course of
(six), re-operation for bleeding (four), pneumonia or chemotherapy for recurrence was 13 months (5–31 months)
empyema (four), reintubation and ventilation (two). It seemed to keep the disease, including ascites (four
Univariate analysis identified age greater than 60 and patients), in check for some months after treatment was
right-sided procedures were associated with major compli- completed and visible reduction of size of subcutaneous
cations following EPP. The major complications following recurrent lumps were noted, but cure was never achieved.
pleurectomy procedures were re-exploration for bleeding
(one), and pneumonia (one). 3.4. Survival

3.2.3. Minor post-operative complications following EPP The median length of follow-up for all 302 patients was
Eighteen patients (28%) had minor complications includ- 16 months (range 0–71 months). The median survival with-
ing atrial dysrhythmia (eight), wound infection (four), out any treatment was 7 months (1–19 moths). Over-all
sputum retention needing bronchoscopy (three), and survival analysis did not show any significant difference
contralateral pneumothorax (one). The median length of between patients who underwent EPP without adjuvant
hospital stay was 17 days. The duration of hospital stay chemotherapy (13 months) when compared to patients
was not affected by the minor complications but was signif- who had a decortication/pleurectomy (14 months) (Fig. 2).
icantly increased with a major complications (29 days). Adjuvant chemotherapy appeared to significantly influ-
ence the survival after EPP. The 1 and 3 years survival
3.2.4. Post-operative chemotoxicity rates were 84 and 48%, respectively, and the median survi-
Including nausea (63%), hair loss (71%), anaemia (32%), val was 35 months (range 0–71 months) for patients who
leukopenia (21%), and thrombocytopenia (9%). Generally, received chemotherapy following EPP. This compared well
myelosuppression was mild to moderate mostly after the with survival rate of 49 and 0% at 1 and 3 years, and a
third or fourth cycle. Most patients with nausea and vomit- median survival of 13 months (range 0–23 months) for
ing responded well to orally administrated anti-emetics those who did not receive systemic chemotherapy following
particularly Ondansetron. Treatment was delayed at times
Table 2
but modification of chemotherapy dose was not needed in Site of recurrence in patients after extrapleural pneumonectomy
any patient.
Site of first recurrence No of patients Percentage
3.3. Recurrence rate Thorax ipsilateral 8 12
Thorax contralateral 5 8
3.3.1. Radical surgery without systemic chemotherapy Liver 8 12
(n ¼ 13) Abdomen/retroperitoneal nodes 7 10
Clinical recurrence was diagnosed after a median period Kidney 2 3
of 10 months (range 8–14 months) in the first 13 patients Adrenals 1 1.5
Brain/nervous system 1 1.5
who did not receive any adjuvuant systemic chemotherapy
Skin 1 1.5
following EPP. The recurrence pattern was aggressive and
302 T. Aziz et al. / European Journal of Cardio-thoracic Surgery 22 (2002) 298–305

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Fig. 2. Actuarial survival of patients after palliative pleurectomy and after Fig. 4. Actuarial survival after extra pleural pneumonectomy and
extra pleural pneumonectomy without chemotherapy compared with after chemotherapy for epitheliod type of Mesothelioma compared to the sarco-
extrapleural pneumonectomy followed by chemotherapy. matous type of disease.

their radical surgery (P ¼ 0:001 and 0.0001 for 1 and 3 of the types. However, there was better trend of survival in
years differences, respectively). (Fig. 3). Eighteen percent favour of epithelial tumours (P ¼ 0:07 at 3 years interval)
(9/51) of our patients who were treated with radical surgery rather than sarcomatous tumours. There was no difference in
followed by systemic chemotherapy have achieved more survival according to differences in age, sex, period of
than 5 years of survival. The univariate analyses of survival asbestos exposure and pre-operative symptoms.
in patients treated with systemic chemotherapy according to
TN status and stages are shown in figures (Figs. 4 and 5).
Comparison of individual T status categories showed signif- 4. Discussion
icant difference in survival for T1 vs. T2, and also signifi-
cant difference was noted for T2 vs. T3. The median The management of MPM remains a subject of contro-
survival for T1 tumour was 42.8 months. This was signifi- versy because of incomplete understanding of its natural
cantly different from the median survival of 31 months and history and apparent resistance to standard forms of therapy.
14 months for T2 and T3, respectively. The survival preva- The treatment of MPM has gained importance because the
lence was 90 and 70% for T1 patients, and 85 and 36% for disease is becoming more prevalent worldwide [3]. The
T2 patients, and 49 and 0% for T3 patients at 1 and 3 years, perceived high operative mortality after EPP was the main
respectively (P ¼ 0:007, 0.002, respectively). reason for reluctance to operate, as early experience from
However, in variance to others’ experience, no significant Butchart et al. [9] cited hospital mortality of 31% (9 out of
difference in survival was noted between N0 and patients 29). Bamler and MaaBeen [10] found a similarly high rate
who had nodal spread (P ¼ 0:08 at 3 years interval). of 24% (4 out of 17). Operative mortality as high as this is
Univariate analysis of survival according to the histological bound to reduce any potential therapeutic effect. Recent
type demonstrated no significant difference between either experience [11–13] confirms that the operative mortality
of EPP although still higher than for a decortication/pleur-
ectomy, is not dissimilar to that for a standard pneumonect-

Fig. 5. Actuarial survival after extra pleural pneumonectomy and


Fig. 3. Actuarial survival after extrapleural pneumonectomy and chemotherapy for malignant mesothelioma with and without lymph node
chemotherapy for disease. Stages I, II and III. involvement as seen at surgery.
T. Aziz et al. / European Journal of Cardio-thoracic Surgery 22 (2002) 298–305 303

omy in the hands of surgeons or single institutions that both Rusch et al. [8,10] and Sugarbaker et al. [22,23], our
perform this operation regularly. In our experience, the results confirm that T1 and T2 patients have a much more
operative mortality was 9.1% (6 out of 64) and continues favourable survival outcome when radical surgery and thus
to improve with only a single mortality in the last 21 patients post-operative chemotherapy has been used. Our data also
and it is comparable with the operative mortality of standard shows that T1 tumour exhibits better long-term survival
pneumonectomy in our centre. outcome than T2 disease. T3 tumour has a poor prognosis
We did not find much difference in survival between even when radical surgical resection was achieved and
patients who underwent decortication/pleurectomy hence, we need to identify these patients before surgery
compared to patients without any surgical intervention. It and avoid operating on them. Tumour T stage does seem
is almost impossible to achieve reasonable degree of surgi- to be an important selection criteria.
cal clearance without radical surgery. Although the pallia- The negative significance of lymph node involvement on
tive effect could not be assessed in this retrospective study, survival following EPP has been illustrated in some bigger
it was not impressive and it was clear that more radical series [25]. The negative influence of lymph node involve-

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intervention was required to get better results. ment in the survival of MPM following radical surgery and
The long-term result after radical surgery alone proved to chemotherapy is not supported by our series. However,
be poor in initial experiences. In the literature [13–17], a 1- some other previous papers were also not been able to
year survival rate of 29–53% is quoted for patients who demonstrate a worse prognosis in patients with lymph
undergo radical resection alone. Survival reported after radi- node involvement [16]. Such contrary findings may be
cal surgery alone is only slightly better than after palliative due to smaller number of study population in our series.
decortication/pleurectomy or palliative care and in our On clinical grounds, we find the CT scan inadequate for
series found early aggressive recurrence in patients who clearly separating lymph nodes from pleural nodules in
were treated by radical surgery alone. Radical surgery the same area, which hinders pre-operative staging. In any
alone in form of EPP with resection of pericardium and case we do not consider lymph node involvement as an
diaphragm without adjuvant therapy did not achieve any absolute contraindication for EPP pre-operatively if the
survival advantage over a palliative decortication/pleurect- patient is considered suitable (T1) and generally fit for
omy with maximum tumour reduction. Therefore, though surgical resection. Entering such patients into clinical trials
the morbidity and mortality of EPP have diminished, the and testing the outcome of radical surgery and chemother-
long-term benefit of radical surgery alone remains doubtful. apy on them would be desirable.
Due to its lower complication rate, pleurectomy/decortica-
tion seemed to be superior to radical surgery alone and
achieved some palliation in reducing pain, and is hence 5. Study limitations
recommended by many authors [14–16]. We can confirm
the same results as previous reports [18–19] about increased Our study is limited by factors, which may affect any
incidence of peritoneal spread and recurrence following retrospective and non-randomised analysis. Systemic
EPP. This is because the diaphragm, which acts as a natural chemotherapy was not offered to patients who underwent
barrier to peritoneal dissemination, has been removed decortication/pleurectomy because complete resection was
during the operation. not possible but this may be worth looking into. The influ-
Various trials of systemic chemotheraputic agents for ence of lymph node metastasis and histopathological type of
management of MPM [20–25] have been performed over MPM may require further studies to validate these findings.
the years, but few have shown clear benefit. Most of the We expect that patients with diffuse MPM suitable for radi-
series have been too small in scale to accurately measure cal resection and post-operative chemotherapy will repre-
the response. Additional problems include heterogeneity of sent only up to 25% of total MPM patients at any institution.
the patient population, difficulty in accurate staging in the Finally, it has to be commented that the decision between
unoperated patient, and a possibility of erroneous pathologic EPP and pleurectomy may be not easy in all MPM patients
diagnosis. Platinum based compounds alone or in combina- particularly those with good general condition, resectable
tion with anthracyclines (Epirubcin) has been proved to be tumour and lymph node metastasis (N1 or N2). The decision
effective in providing the response rates between 10 and in these cases will be mainly based on the subjective impres-
20% in several European studies [23–24]. The first experi- sion of the individual surgeon and sometimes on findings on
ence of intrapleural chemotherapy was reported by Rice et the table.
al. [13] in a group of 19 patients treated with intrapleural This study did not include a proper quality of life assess-
chemotherapy following pleurectomy or EPP, however, ment of patients after their major operative procedure nor
local recurrence was very common in their group. Although after their chemotherapy. This is needed to establish the true
the intrapleural regime avoided the systemic side effect of benefits of this regime. However, the toxicity was not over-
chemotherapy, it did not reduce the incidence of local or whelming at the post-operative course and most patients
distant recurrence of the disease. seemed to enjoy a good standard of life including work
In agreement with previous bigger studies reported by and foreign holidays during their disease free period. Pain
304 T. Aziz et al. / European Journal of Cardio-thoracic Surgery 22 (2002) 298–305

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1997;63:334–338. Dr H. Toomes (Stuttgart, Germany): You have a really big clinical
[6] Buchart EG, Ashcroft T, Barnsley WC, Holden MP. Pleuropneumo- material. I want to ask you about radically operated patients. You had
nectomy in the management of diffuse malignant mesothelioma of the 64 radically operated and you lost some patients through mortality and
pleura. Experience with 29 patients. Thorax 1976;31:321–328. follow-up, and then 51 patients you had follow-up on, and, of them, you
[7] Balmer K-J, Maabeen W. Uber die verteilung der beingnen und had a five-year survival of 28%. You corrected it. And if I followed the
malignen pleuratumoren in Krankengut einer lungenchirugischen figures, I come to a five-year survival of about 23% in your material.
Klinik mit besonderer Berucksichtigung des malignen pleurome- Those are figures that we normally achieve without chemotherapy with
sotheliomas und seiner radiklen behandlung einschlieblich der a radical operation.
Ergebnlsse des Zwerchfellersatzes mit konservierter Dura mater. My question is, how can you prove that the chemotherapy has a profit for
Thorxchirurgie 1974;222:386–391. the patient?
[8] Rusch VW, Venkatraman E. The importance of surgical resection in Dr Prakash: Our series of 64 patients is divided into two groups, not
the treatment of malignant mesothelioma. J Thorac Cardiovasc Surg randomised, I admit, but the first group of patients did badly without
1996;111:815–826. chemotherapy, and we did not have a two-year survival in them. The
T. Aziz et al. / European Journal of Cardio-thoracic Surgery 22 (2002) 298–305 305

recurrence, when it occurred, was very vigorous, aggressive, and some of were operated by extrapleural pneumonectomy or did you have long-term
the patients died within weeks of recurrence occurring. In the second group survivors in other categories?
of patients, we do have long-term survivors, and although 31 patients had Dr Prakash: I didn’t get your second question.
recurrence, the recurrence was still treatable, we gave them a further course Dr Ris: The second question was, in these long-term survivors, were
of chemotherapy, which seemed to control the disease for a short period of these all patients who were treated by extrapleural pneumonectomy?
time, for a few months, before they died. Dr Prakash: Yes. Our long-term survivors was 9, not the figure you
Dr Toomes: The treatment of mesothelioma is also a question of selec- mentioned. I corrected myself. The long-term survival was 18%, or 9
tion, and, as you said, Sugarbaker has selected subgroups, and in subgroups patients, in the group with chemotherapy. And there were no special char-
with epithelial mesothelioma with only surgical treatment, he achieves a acteristics in these 9 patients that we were able to pick up: some of them did
46% five-year survival. Do you want to comment on this? have nodal involvement and some of them were sarcomatous.
Dr Prakash: We have not been as selective, we have not ruled out Dr D. Dougenis (Patras, Greece): Why do you consider a contraindica-
surgery for sarcomatous patients at this stage. In the future, one may tion to a radical extrapleural pneumonectomy the invasion of the
want to consider that. But I think we do have sarcomatous patients surviv- diaphragm? Do you remove the diaphragm along with the entire lung
ing long term, and we felt we should not deprive them of surgical treat- during the procedure?
ment. Dr Prakash: Yes, we do remove the diaphragm. We do preserve the
Dr H. Aebert: (Tubingen, Germany): I have a question relating to your underlying diaphragmatic peritoneum wherever possible. We feel that if

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patients just receiving biopsy and best supportive care. Did you radiate the the diaphragm itself has been invaded on CT findings, the chances are that
biopsy site, and how many local recurrences did you have? the underlying peritoneum may be involved and therefore the chance of the
Dr Prakash: We did not radiate the biopsy sites. The local chest wall patient doing well is less. So we don’t choose to operate on these patients at
recurrences was small, I don’t have a figure at the moment, but the number the moment.
was small, and more importantly, these chest wall recurrences were neither Dr H. Toomes: What kind of material do you use for the replacement of
painful nor very problematic; they didn’t ulcerate through the skin and so the diaphragm?
on like some other tumors. So we didn’t actively treat or prevent them. Dr Prakash: The diaphragm is replaced by a two-way stretch Dacron
Dr H. Ris: (Lausanne, Switzerland): You had 18 long-term survivors in material sewn all around at the level of the thoracotomy rather than the
your series. Could you please comment on the pathological pattern of this original level of the diaphragm. We use mercilene mesh loosely applied for
disease in these patients? And the second question, whether all patients replacing the pericardium.

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