European Journal of Cardio-thoracic Surgery

About the journal

Publisher: Oxford University Press
Published: 1987 to the present, Germany
Language: English
ISSN: 1010-7940 (print), 1873-734X (electronic)
Its record in the NLM Catalog

2020s

Risk factors influencing postoperative pleural empyema in patients with pleural mesothelioma: a retrospective single-centre analysis. P. Henschke, L.C. Guglielmetti, S. Hillinger, et al. 2024;65(4). PubMed · Publisher · Free full text

Abstract

Objectives: Postoperative empyema is a severe, potentially lethal complication also present, but poorly studied in patients undergoing surgery for pleural mesothelioma. We aimed to analyse which perioperative characteristics might be associated with an increased risk for postoperative empyema.

Methods: From September 1999 to February 2023 a retrospective analysis of consecutive patients undergoing surgery for pleural mesothelioma at the University Hospital of Zurich was performed. Uni- and multivariable logistic regression was used to identify associated risk factors of postoperative empyema after surgery.

Results: A total of 400 PM patients were included in the analysis, of which n = 50 patients developed empyema after surgery (12.5%). Baseline demographics were comparable between patients with (Eyes) and without empyema (Eno). 39% (n = 156) patients underwent extrapleural pneumonectomy (EPP), of whom 22% (n = 35) developed postoperative pleural empyema; 6% (n = 15) of the remaining 244 patients undergoing pleurectomy and decortication (n = 46), extended pleurectomy and decortication (n = 114), partial pleurectomy (n = 54) or explorative thoracotomy (n = 30) resulted in postoperative empyema. In multivariable logistic regression analysis, EPP (odds ratio 2.8, 95% confidence interval 1.5-5.4, P = 0.002) emerged as the only risk factor associated with postoperative empyema when controlled for smoking status. Median overall survival was significantly worse for Eyes (16 months, interquartile range 5-27 months) than for Eno (18 months, interquartile range 8-35 months).

Conclusions: Patients undergoing EPP had a significantly higher risk of developing postoperative pleural empyema compared to patients undergoing other surgery types. Survival of patients with empyema was significantly shorter.

© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.
Surgery for pleural mesothelioma in multimodality setting: comparison between surgical techniques in a high-volume centre. E. Faccioli, A. Dell'Amore, G. Lorenzoni, et al. 2024;66(6). PubMed · Publisher

Abstract

Objectives: Pleural mesothelioma (PM) is an aggressive disease linked to asbestos exposure, presenting significant treatment challenges. The recommended approach is multimodal treatment, even if the concept of resectable PM and the superiority of one surgical technique over the other [(extended) pleurectomy decortication [(E)PD] vs extra-pleural pneumonectomy (EPP)] are matter of debates. The aim of this study is to compare the 2 techniques in terms of short- and long-term outcomes at a high-volume centre.

Methods: Clinical data from PM patients who underwent radical surgery [(E)PD and EPP] between 1994 and 2022 were collected. A propensity score weighting approach was used for non-random intervention allocation. Survival distribution was estimated using Kaplan-Meier method and the association with outcomes was evaluated using a weighted Cox proportional hazard models.

Results: Among 254 patients, 125 (49%) underwent EPP and 129 (51%) (E)PD. The 90-day mortality was higher in the EPP group (7.2% vs 0%; P = 0.01). No difference in 1-, 3- and 5-year survival was found: 65.8%, 26%, 17% for EPP and 75.5%, 39.7% and 21.3% for (E)PD; P = 0.39. The multivariable-weighted Cox model identified no increased risk of death [hazard ratio (HR) 1.25; P = 0.49] or recurrence (HR 1.05; P = 0.858) in the EPP group. Pre-operative total lung capacity was significantly associated with a reduced risk of death (HR 0.96; P = 0.023) and recurrence (HR 0.97; P = 0.019) at follow-up, while pre-operative disease burden to a higher risk of recurrence (HR 1.01; P = 0.02).

Conclusions: Our experience showed acceptable short- and long-term outcomes in both procedures, making EPP still an option only for carefully selected patients at high-volume centre. Surgery, although recently debated, should be performed exclusively in expert centres to minimize post-operative risks. The identification of new prognostic factors is crucial for better selecting patients who may benefit from surgery within the context of multimodal treatment.

© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Prospective validation and extension of the Multimodality Prognostic Score for the treatment allocation of pleural mesothelioma patients. D. Greb, M. Hebeisen, A. Matter, et al. 2022;62(2). PubMed · Publisher · Free full text

Abstract

Objectives: Patient allocation to multimodality treatment in patients with malignant pleural mesothelioma remains a challenge. The aim of this study was to validate our previously established Multimodality Prognostic Score (MMPS) (tumour volume before chemotherapy, histological subtype, C-reactive protein before chemotherapy and tumour progression after chemotherapy) and to extend the score with additional blood parameters for better patient outcome.

Methods: Patients with histologically proven malignant pleural mesothelioma and curative intended therapy with clinical stage T1-T3 N0-N2 M0 were eligible. The existing MMPS was validated and further additional blood markers (erythrocytes, neutrophils, monocytes, albumin, gamma-glutamyl transferase and alkaline phosphatase) were evaluated for potential incorporation.

Results: For the validation of the existing MMPS, as the first part of this analysis, 117 patients treated as of September 2011 were included. A total of 88 patients were treated with macroscopic complete resection, whereas 29 patients were treated with palliative or no surgery. Patients treated with macroscopic complete resection and a high MMPS showed statistically significant lower overall survival. In the second part, the extension of the MMPS with additional blood parameters was analysed. Albumin, the only parameter showing evidence for having influence on overall survival, was further added to the extended MMPS. When comparing the performance measures Area under the curve (AUC) and Brier score, the extended score performed better (higher AUC, lower Brier score) than the original MMPS.

Conclusions: The extended score with albumin showed improved performance in comparison to the original score. The extended MMPS also may help allocating patients to surgery.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.

2010s

An insidious cause of spontaneous pneumothorax in an elderly woman. F. Lococo, G. Marchesini, S. Taddei, et al. 2016;49(3):e63-4. Case report PubMed · Publisher
Comorbidity, postoperative morbidity and survival in patients undergoing radical surgery for malignant pleural mesothelioma. M. Infante, E. Morenghi, E. Bottoni, et al. 2016;50(6):1077-1082. PubMed · Publisher

Abstract

Objectives: We examined a series of malignant pleural mesothelioma (MPM) patients who underwent radical surgery to explore relationships among comorbidity, postoperative morbidity and survival.

Methods: A retrospective analysis was carried out of all MPM patients operated on in a single centre from 2000 to 2015. The Charlson Comorbidity Index (CCI) was used to classify patients according to their underlying condition. Postoperative complications were scored according to WHO-derived criteria. Survival comparisons were performed by Cox analysis.

Results: Ninety-one patients underwent extrapleural pneumonectomy (EPP), 47 underwent pleurectomy decortication (PD) and 25 underwent palliative pleurectomy. The mean CCI of PD patients was significantly higher compared with that of EPP patients (P= 0.044). The frequency of grade 3+ complications was similar between EPP and PD (27 vs 26%). However, EPP patients had a 6-fold higher frequency of pleural sepsis (24 vs 4%, P= 0.002) occurring up to 695 days postoperatively. Median overall survival was 19 months (95% CI 13-25) after EPP, 30 months (95% CI 20-35) after PD and 13 months (95% CI 5-32) after palliative pleurectomy. At multivariate analysis, CCI (P< 0.001), histology (P= 0.014) and pleural sepsis (P= 0.001), but not complete resection, were significantly associated with survival. There was a trend in favour of PD over palliative resection after adjusting for histology and CCI.

Conclusions: The CCI is an independent predictor of survival in MPM patients undergoing radical surgery. Owing to its significant frequency and adverse impact, pleural sepsis may contribute to a reduced life expectancy after EPP. Surgical treatment of MPM remains debatable.

© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Impact of induction therapy on postoperative outcome after extrapleural pneumonectomy for malignant pleural mesothelioma: does induction-accelerated hemithoracic radiation increase the surgical risk?. P. Mordant, K. McRae, J. Cho, et al. 2016;50(3):433-8. PubMed · Publisher

Abstract

Objectives: Patients with malignant pleural mesothelioma (MPM) eligible for extrapleural pneumonectomy (EPP) may benefit from induction chemotherapy (CT) as historically described, or from induction-accelerated hemithoracic intensity-modulated radiation therapy (IMRT) as a potential alternative. However, the impact of the type of induction therapy on postoperative morbidity and mortality remains unknown.

Methods: We performed a retrospective study including every patient who underwent EPP for MPM in our institution between January 2001 and December 2014. Patients without induction treatment (n = 7) or undergoing both induction CT and IMRT (n = 2) were then excluded. The remaining patients (study group) were divided according to the type of induction treatment in Group 1-CT and Group 2-IMRT. Major complications were defined by complications of Grade 3 or higher according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 guidelines. Red blood cell (RBC) transfusion was analysed as a number of packs, and dichotomized as <3 vs ≥3 packs. Plasma and platelet transfusion were analysed as a number of units, and dichotomized as no transfusion versus any plasma or platelet transfusion.

Results: Altogether, 126 patients (mean age 61.3 ± 8.1 years, males 82.5%, right side 60.3%, 90-day mortality rate 4.8%) accounted for the study group. Sixty-four patients were included in Group 1-CT and 62 patients were included in Group 2-IMRT. When compared with Group 1-CT, Group 2-IMRT was characterized by older patients (59.3 ± 9.2 vs 63.3 ± 8.3 years, P = 0.012), more right-sided resections (46.8 vs 74.1%, P = 0.003), more advanced disease (pathological stage IV: 28.1 vs 53.2%, P = 0.007), less RBC transfusions (5.1 ± 3.0 vs 3.0 ± 2.4 packs, P < 0.001), less plasma or platelet transfusions (31.2 vs 9.6%, P = 0.005) and similar rate of major complications (29.6 vs 35.4%, P = 0.614). The 90-day mortality rate was 6.2% in Group 1-CT (n = 4) and 3.2% in Group 2-RT (n = 2, P = 0.680). Induction with IMRT was significantly associated with a decreased risk of transfusion with RBCs [odds ratio (OR) = 0.10, 95% confidence interval (CI) 0.04-0.23, P < 0.001] as well as plasma and platelets (OR = 0.25, 95% CI 0.086-0.67, P = 0.008).

Conclusions: In this large single-centre series of EPP for MPM, the implementation of induction IMRT was not associated with any significant increase in the surgical risks above and beyond induction CT. The switch from induction CT to induction IMRT was associated with resection in older patients with more advanced tumours, less transfusion requirements, comparable postoperative morbidity and 90-day mortality.

© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Relapse pattern and second-line treatment following multimodality treatment for malignant pleural mesothelioma. A. Kostron, M. Friess, O. Crameri, et al. 2016;49(5):1516-23. PubMed · Publisher

Abstract

Objectives: To analyse the relapse pattern and influence of second-line treatment after recurrence of malignant pleural mesothelioma (MPM) in patients who had previously undergone multimodality treatment.

Methods: Between September 1999 and December 2013, 136 patients underwent macroscopic complete resection (MCR) by extrapleural pneumonectomy after induction chemotherapy for MPM. We analysed 106 patients who presented with recurrent disease until October 2014. Data were retrieved from our mesothelioma database, with additional information regarding precise localization gathered by reviewing the imaging and medical records.

Results: The overall recurrence rate was 78% (106/136 patients). The median freedom from recurrence was 9 months after surgery [95% confidence interval (95% CI) 7-10]. Local recurrence only was observed in 33 patients (31%), distant metastases only in 27 patients (26%) and simultaneous distant and local recurrence in 46 patients (43%). Local recurrence was observed significantly less frequently in patients having received adjuvant radiotherapy (19 vs 47%, P = 0.003), but there was no significant impact on overall survival (OS) [radiation: 22 months (95% CI 19-24); no-radiation: 23 months (95% CI 18-27), P = 0.6]. The median OS was 22 months (95% CI 21-24), median post-recurrence survival (PRS) was 7 months (95% CI 5-9) and patients with local recurrence only survived significantly longer (12 months, 95% CI 8-16) compared with patients with distant recurrence only (5 months, 95% CI 2-8) or distant plus local relapse (6 months, 95% CI 3-9; P = 0.04). A total of 78 patients received a second-line therapy after tumour recurrence: chemotherapy (n = 48), local radiotherapy (n = 9), surgery (n = 10) or a combination thereof (n = 11). Patients undergoing second-line treatment survived significantly longer compared with patients not receiving therapy (P < 0.0005). The median PRS after surgery was significantly longer than that of patients receiving chemo-, radio- or chemo-radiotherapy (P = 0.04).

Conclusions: Local recurrence of MPM remains the most frequent type of relapse even after multimodality treatment including MCR. In the present cohort, active treatment seems beneficial to the patient since surgical excision of local tumour relapse has good long-term outcome in selected patients. Thus, second-line treatment may prolong PRS; however, these results need to be confirmed in a prospective manner.

© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Specimen weight and volume: important predictors of survival in malignant pleural mesothelioma. D.Y. Kircheva, A.N. Husain, S. Watson, et al. 2016;49(6):1642-7. PubMed · Publisher

Abstract

Objectives: The tumour/node/metastasis (TNM) staging system for malignant pleural mesothelioma (MPM) is a worldwide standard, but has many limitations. Tumour volume has been suggested as a predictor of survival. Due to the complex anatomy, estimation of tumour volume via CT scan can be challenging. Surgical volume may be more accurate. Therefore, we prospectively determined resected specimen volumes and weights in consecutive patients undergoing extended pleurectomy and decortication (EPD) and correlated this with overall survival and T and N stage.

Methods: We evaluated 116 patients undergoing EPD for MPM in a single university centre over a 6-year period. All resected specimens were weighed, and the volume was measured by a fluid displacement method. A Cox regression model was used to identify significant predictors of survival; hazard ratios were calculated. A Kaplan-Meier method was used to summarize overall and subgroup survival. Logistic regression models were used to identify predictors of T and N stage.

Results: There were 95 males and 21 females with a median age of 68 range 43-88 years. Forty-one patients had an ECOG performance status (PS) 0, 70 had 1 and 4 had 2. The median time between initial diagnosis and surgery was 134 days. Histology was epithelioid in 59, biphasic in 55 and sarcomatoid in 2. The mean volume was 641 ml with an SD of 393.34 ml. The median volume was 567.5 ml. The mean weight was 620.8 g with an SD of 361.92 g. The median weight was 552.0 g. Two-year survival from initial diagnosis and from EPD was 44 and 28%, respectively. PS (P = 0.002), epithelioid histology (P < 0.001), specimen weight (P < 0.001), volume (P < 0.001), platelet count (P = 0.015), T1 stage (P = 0.04) and adjuvant therapy (P = 01) were predictive of survival. Tumour volume was a predictor of T stage (P = 0.048) and survival (P = 0.03). There was no relationship between N stage and tumour volume, weight or histology.

Conclusions: PS, specimen weight, volume, epithelioid histology platelet count and adjuvant chemotherapy are significant predictors of survival in patients undergoing EPD for MPM. There is a correlation between specimen volume and T stage. These data suggest that tumour weight and volume may be valuable components for staging MPM.

© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Spinal cord ischaemia after radical pleurectomy/decortication operation for mesothelioma. E. Kaba, M.O. Özyurtkan, L. Onat, et al. 2016;50(6):1212-1214. Case report PubMed · Publisher

Abstract

Radical pleurectomy/decortication was performed in a patient with malignant pleural mesothelioma. During the surgery, the left subclavian artery was injured, and repaired via resection and anastomosis. However, the patient was diagnosed with paraplegia following extubation. After deliberate investigations, the mechanism of injury to the critical vascular zone of the spinal cord was determined. Here, we aim to draw attention to possible similar injuries.

© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
The effects of an intentional transition from extrapleural pneumonectomy to extended pleurectomy/decortication. A.J. Sharkey, S. Tenconi, A. Nakas, et al. 2016;49(6):1632-41. PubMed · Publisher

Abstract

Objectives: For many years, extrapleural pneumonectomy (EPP) was the operation of choice for the radical management of pleural mesothelioma in the UK. However, doubts surrounding the efficacy of EPP, and the change in demographics of the affected population, have prompted a transition in our practice towards extended pleurectomy/decortication (EPD). The aim of this study was to determine the effects an intentional transition from EPP to EPD has had on patient outcome.

Methods: Data from 362 patients undergoing radical surgery (229 EPD, 133 EPP) during 1999-2014 were included. Demographics and outcome were compared between the two groups; EPP versus EPD.

Results: The median age of patients undergoing EPD was significantly higher than those undergoing EPP [57 years (range 14-70 years) vs 65 years (range 42-81 years), P < 0.001]. There was a significantly higher proportion of patients with performance status ≥1 in the EPD group (46.3 vs 35.4%, P = 0.047). There was no difference in the median length of hospital stay between the two groups [14 days (range 1-133 days) vs 13 days (range 0-93 days), P = 0.409]. There was also no difference between the groups in terms of in-hospital mortality (EPP 5.3% and EPD 6.6%, P = 0.389), 30-day mortality [EPP 8 (6.0%) and EPD 8 (3.5%), P = 0.294] or 90-day mortality [EPP 18 (13.5%) and EPD 21 (9.2%), P = 0.220]. There was a significantly higher early reoperation rate in the EPP group (15.0 vs 6.2%, P = 0.008) but a significantly higher late reoperation rate in the EPD group (0.8 vs 5.3%, P = 0.037). There was no significant difference in overall survival or disease-free interval between the two groups (P = 0.899 and P = 0.399, respectively). However, overall survival was significantly greater in patients over the age of 65 undergoing EPD (12.5 vs 4.7 months, P = 0.001).

Conclusion: The transition from EPP to EPD in our standard practice has enabled us to operate on more elderly, frail patients with no significant increase in use of hospital resources, and without detriment to overall survival.

© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

In plain English

This retrospective study at one centre in Leicester, UK, compared 362 consecutive patients with malignant pleural mesothelioma who had radical surgery between 1999 and 2014. Of these, 133 had extrapleural pneumonectomy (EPP), which removes the lung, and 229 had extended pleurectomy/decortication (EPD), which preserves it. The study compared operations; it did not study asbestos exposure. EPD patients were older (median 65 vs 57 years) and more often had performance status 1 or worse (46.3% vs 35.4%). Hospital stay, deaths in hospital, at 30 days and at 90 days, and overall survival (median 12.9 months EPP, 12.3 months EPD) did not differ significantly. Early reoperations were more common after EPP (15.0% vs 6.2%). Late reoperations were more common after EPD (5.3% vs 0.8%). Among 139 patients over 65, median survival was 12.5 months after EPD and 4.7 months after EPP; only 16 had EPP. The authors concluded the switch let them operate on older patients with poorer performance status without increasing complications and deaths or affecting long-term survival. They cautioned that the retrospective design and selection bias limit these conclusions.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.
The management of the diaphragm during radical surgery for malignant pleural mesothelioma. A.J. Sharkey, R. Bilancia, S. Tenconi, et al. 2016;50(2):311-6. PubMed · Publisher

Abstract

Objectives: Macroscopic complete resection with lung preservation is the objective of radical management of pleural mesothelioma (MPM). Total removal of visceral and parietal pleura (pleurectomy/decortication) almost invariably proceeds to an extended pleurectomy/decortication (EPD) to ensure macroscopic complete resection. We suspected this may not always be necessary.

Methods: We reviewed 314 patients, 86.0% male, median age 62 years (range 14-81 years) undergoing radical surgery for MPM from 1999 to 2014, by either EPD or extrapleural pneumonectomy. The extent of diaphragmatic muscle involvement was recorded from postoperative pathology. Patients were divided into three groups: no involvement, non-transmural, transmural diaphragmatic invasion.

Results: A total of 213 (68%) patients underwent EPD, 237 (75.5%) had epithelioid disease and 57.6% were node positive. There was no difference between the three groups in terms of age, cell type, laterality, neoadjuvant chemotherapy and operation. There was a higher degree of diaphragm involvement in females (P = 0.01) and in patients with positive lymph nodes (P = 0.01). No evidence of diaphragmatic involvement was found following pathological assessment of the resection specimen in 119 patients (37.9%). The incidence of abdominal disease progression was 23.9%. There was no correlation with degree of diaphragmatic invasion (ρ = 0.01 P = 0.88). Overall survival of those with abdominal progression was similar to those with progression elsewhere: 14.5 vs 13.0 months (P = 0.79), and with those with no progression (16.7 months, P = 0.189). There was no difference in survival when stratified by diaphragmatic involvement (P = 0.44).

Conclusions: In our cohort, there was no evidence of diaphragmatic invasion in over 30% of patients, and we have also failed to find evidence that peritoneal disease progression affects overall survival following radical management. It may therefore theoretically be unnecessary to resect the diaphragm in all cases, and a pleurectomy-decortication could suffice. However, there is an unknown risk of R2 resection which would prejudice survival, and as such we would advocate resecting the diaphragm in all cases to avoid an R2 resection.

© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
The staging of malignant pleural mesothelioma: are we any nearer to squaring the circle?. D.A. Waller. 2016;49(6):1648-9. Editorial · Comment PubMed · Publisher

Summary

This editorial comment, by a thoracic surgeon in Leicester, UK, discussed the staging of malignant pleural mesothelioma (MPM). It responded to a study by Kircheva et al. that proposed resected specimen weight and volume as predictors of survival. The author argued that accurate staging at presentation was essential for deciding who would benefit from radical surgery and for designing and interpreting clinical trials. He noted that current T descriptors were descriptive and best suited to surgical and pathological staging. He reviewed pretreatment imaging measures, including tumour thickness, CT-based tumour volume and FDG-PET total glycolytic volume. He identified limitations in the Kircheva study: a high proportion (49%) of non-epithelioid tumours, acceptance of 5% R2 resection, a low rate of pN0 disease (40%) despite 71% of cases being staged pT3/4, 15% of cases staged pNX, and no description of the nodal dissection technique. He argued that nodal metastasis remained key to prognosis in epithelioid MPM and that such disease should be classed simply as node-negative or node-positive. He supported histological nodal staging by endobronchial ultrasound or cervical mediastinoscopy before radical surgery. He concluded that biological markers would eventually supersede anatomical staging. For now, he said, surgeons should rely on accurate imaging, invasive preoperative nodal staging and intraoperative systematic nodal dissection. Specimen weight might become a useful adjunct after further validation.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Assessment of cisplatin concentration and depth of penetration in human lung tissue after hyperthermic exposure. M. Ried, K. Lehle, R. Neu, et al. 2015;47(3):563-6. PubMed · Publisher

Abstract

Objectives: The effects of cisplatin on the lung parenchyma during hyperthermic intrathoracic chemotherapy perfusion have not been analysed in detail. The objective of this study was to evaluate both the concentration and depth of the penetration of cisplatin in human lung tissue after hyperthermic exposure under ex vivo conditions.

Methods: This experimental study was approved by the local ethics committee. Twelve patients underwent pulmonary wedge resections after elective thoracic lobectomies were performed (resected lobe), and the lung tissue (approximately 1-2 cm(3)) was incubated (in vitro) with cisplatin (0.05 mg/ml; 60 min, 42°C). Subsequent tissue beds (depth, 0.5 mm; median weight, 70-92 mg) were prepared from the outside to the middle, and the amount of cisplatin per tissue weight was analysed using atomic absorption spectrometry. Afterwards, the penetration of cisplatin depth was calculated and related to the different concentrations per tissue.

Results: Cisplatin penetrated into the human lung tissue after ex vivo hyperthermic exposure. The median amount of platinum [nmol cisplatin/g lung tissue] decreased significantly (P ≤ 0.05) depending on the penetration depth: 32 nmol/g (1 mm), 20 nmol/g (2 mm) and 6.8 nmol/g (4 mm). The calculated median concentrations of cisplatin (µg/ml) were 2.4 µg/ml (1 mm), 1.4 µg/ml (2 mm) and 0.5 µg/ml (4 mm), respectively.

Conclusions: Under ex vivo hyperthermic conditions, cisplatin diffused into human lung tissue. The median penetration depth of the cisplatin was approximately 3-4 mm. The penetration of cisplatin into lung tissue may affect the local therapy of residual tumour cells on the lung surface using hyperthermic intrathoracic chemotherapy perfusion in patients with malignant pleural tumours.

© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Antineoplastic activity of povidone-iodine on different mesothelioma cell lines: results of in vitro study. A. Fiorelli, F. Pentimalli, V. D'Urso, et al. 2014;45(6):993-1000. PubMed · Publisher · Free full text

Abstract

Objective: Povidone-iodine (PVP-I) or Betadine, owing to its antineoplastic activity, is also used as an adjuvant during intra-abdominal or intrathoracic surgery. However, the protocol of PVP-I administration has not been optimized to achieve the best antitumoural efficacy. We aimed to determine the optimal concentration of PVP-I, the time of incubation and the mechanism of cell death by analysing the effect of different doses and time of administration of PVP-I on the cell viability of different mesothelioma cell lines.

Methods: Four different cell lines (MET 5A/normal mesothelium; H2052/sarcomatoid mesothelioma; ISTMES2/epithelial mesothelioma; MSTO/biphasic mesothelioma) were incubated with increasing concentrations of diluted PVP-I (0.0001; 0.001; 0.01; 0.1; 1%) for 5, 10, 30, 60 min and 24 h, respectively. Cell viability was determined using cell direct cytotoxicity assay and cell death was determined through flow cytometry assay analysis. The superoxide dismutase activity was assessed functionally through a specific inhibitor to evaluate the mechanism of cell death.

Results: The antiproliferative effect of PVP-I varied largely among different cell lines in a dose- and time-dependent manner. At 0.1% concentration for 10 min of incubation, the percentage of viable cells was 0.5 ± 0.1; 0.8 ± 0.5 and 0% (P < 0.01) for MET5A, ISTMES2 and MSTO, respectively. Conversely, the same concentration did not significantly affect the H2052 cell line which was completely suppressed at a 1% concentration of PVP-I. Double staining of Annexin V and DNA showed that PVP-I induced cell death in all four cell lines via necrosis depending on PVP-I concentration. However, H2052 was found to be more resistant than MSTO, ISTMES2 and MET 5A cells lines. The activity of superoxide dismutase was significantly inhibited in all cell lines.

Conclusions: Our results confirmed the anti-neoplastic activity of PVP-I especially on ISTMES2 and MSTO cell lines. With respect to chemotherapy pleural irrigation, washing with PVP-I is cost-effective and easy. If confirmed by larger studies, our findings suggest that the intrapleural irrigation with PVP-I (0.1% concentration for 10 min) in patients with epithelial or biphasic mesothelioma undergoing cytoreductive surgery might be applied in thoracic surgery practice to prevent neoplastic cell growth.

© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Biomolecular and clinical practice in malignant pleural mesothelioma and lung cancer: what thoracic surgeons should know. I. Opitz, R. Bueno, E. Lim, et al. 2014;46(4):602-6. Review PubMed · Publisher · Free full text

Abstract

Today, molecular-profile-directed therapy is a guiding principle of modern thoracic oncology. The knowledge of new biomolecular technology applied to the diagnosis, prognosis, and treatment of lung cancer and mesothelioma should be part of the 21st century thoracic surgeons' professional competence. The European Society of Thoracic Surgeons (ESTS) Biology Club aims at providing a comprehensive insight into the basic biology of the diseases we are treating. During the 2013 ESTS Annual Meeting, different experts of the field presented the current knowledge about diagnostic and prognostic biomarkers in malignant pleural mesothelioma including new perspectives as well as the role and potential application of microRNA and genomic sequencing for lung cancer, which are summarized in the present article.

© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Predictors of long-term survival following radical surgery for malignant pleural mesothelioma. A. Nakas, D. Waller. 2014;46(3):380-5; discussion 385. PubMed · Publisher

Abstract

Objectives: The aim of radical surgery for malignant pleural mesothelioma (MPM) is to achieve greater survival than from chemotherapy alone. Although adverse overall prognostic factors have already been determined, our aim was to identify the most important factors affecting long-term survival arbitrarily defined as >24 months.

Methods: We retrospectively reviewed the records of 252 patients (35 females; 193 epithelioid and 59 biphasic; 112 extrapleural pneumonectomy (EPP); 140 extended pleurectomy decortication (EPD)) who survived for at least 90 postoperative days. We tested for factors affecting overall cancer-related mortality and specific clinical factors predicting the 24-month survival.

Results: The overall median survival was 18.2 (SE 1.3, 95% CI 15.8-20.7 months). There was no difference in survival between EPP and EPD (P = 0.92). One hundred and twenty-eight patients received induction, adjuvant or palliative chemotherapy. Seventy-seven (30.6%) patients survived for >24 months. On univariate analysis, age at operation over 60 years (P = 0.044), pT4 stage (P = 0.041), any lymph node metastases (P = 0.002), biphasic cell type (P = 0.00) and no administration of chemotherapy (P = 0.00) were associated with decreased survival. On multivariate analysis, age <60 (P = 0.018, OR = 0.7), epithelioid disease (P = 0.001, OR = 0.56) and negative nodes (P = 0.009, OR = 0.67) were associated with increased survival and no administration of chemotherapy (P = 0.00, OR = 1.9) with decreased survival. Factors predicting survival over 24 months included: age at operation under 60 (P = 0.014), epithelioid histology (P ≤ 0.00), negative nodes (P = 0.002) and chemotherapy (P = 0.022).

Conclusions: These results support a policy of accurate preoperative tissue diagnosis, nodal staging and induction chemotherapy prior to radical surgery for MPM, which can result in long-term survival. Trials investigating the role of surgery should be focused on confirming and refining these selection criteria.

© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Surgery for malignant pleural mesothelioma: why we need controlled trials. T. Treasure, M. Dusmet, F. Fiorentino, et al. 2014;45(4):591-2. Editorial PubMed · Publisher

Summary

In this editorial, the authors argued that randomized controlled trials (RCTs) are needed to judge whether surgery benefits patients with malignant pleural mesothelioma. They stated that observational follow-up studies can mislead, particularly when patients are highly selected and success is judged on completed treatments rather than intention to treat. They described two analyses of existing data. In the first, of 945 patients, those who had no surgery (387), thoracotomy without resection (174) or resection without further cancer treatment (177) had similar average survival of 17–18 months. The 207 who had multimodal treatment averaged 33 months. The authors said selection could contribute to this difference and that a benefit of surgery was not evident. In the second, 10 of 123 patients (8%) in the Cancer Registry of York Teaching Hospital had extrapleural pneumonectomy. When unoperated patients with sarcomatoid histology, poorer performance status or older age were removed stepwise, the survival gap progressively narrowed. The authors explained that RCTs usually show smaller differences than follow-up studies because all allocated patients are analysed and controls are comparable. They described MARS 2, an RCT comparing extended pleurectomy/decortication (e-P/D) plus platinum-pemetrexed chemotherapy with chemotherapy alone. They noted that the EORTC study, which tests only the timing of e-P/D, cannot show whether e-P/D is effective. They concluded that randomized trials are needed.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Changes in pulmonary function tests predict radiological response to chemotherapy in malignant pleural mesothelioma. G. Marulli, F. Di Chiara, F. Braccioni, et al. 2013;44(1):104-10. PubMed · Publisher

Abstract

Objectives: Response to chemotherapy in malignant pleural mesothelioma (MPM) is usually evaluated by radiological criteria, but no common agreement exists on their validity, yet. The cytoreductive effect of chemotherapy on pleural thickening may make the lung more expansible, reducing the restrictive ventilatory impairment. The aim of this study was to evaluate the changes in pulmonary function following chemotherapy in patients with MPM and to correlate these findings with radiological changes.

Methods: Between 2004 and 2011, 62 consecutive patients (74% males, median age 63 years) were prospectively investigated. Modified RECIST criteria were used for radiological evaluation of response to chemotherapy. All patients underwent pulmonary function tests before and after three cycles of platinum-based chemotherapy. Changes between baseline and post-chemotherapy pulmonary function values (Δ) and their differences were assessed by means of Student's paired and unpaired t-test, respectively. Receiver operating characteristic (ROC) curve analysis was performed on spirometric parameters significantly associated with response.

Results: Thirty (48.4%) patients had a radiological stable disease (S), 23 (37.1%) a partial response (R) and 9 (14.5%) a progressive disease (P). ΔFEV1%pred (R: 18.1 ± 18.5%; S: 0.5 ± 9.3%; P: -11 ± 13.5%; P < 0.0001), ΔFVC%pred (R: 16.1 ± 11.8%; S: 0.4 ± 11.2%; P: -9.2 ± 14.6%; P < 0.0001) and ΔVC%pred (R: 12.9 ± 15.7%; S: 1.5 ± 12.1%; P: -6.1 ± 13.2%; P = 0.001) were significantly associated with radiological response. A significant correlation was observed between ΔFEV1%pred (r = 0.46, P = 0.01), ΔFVC%pred (r = 0.43, P = 0.02) and % change in linear tumour measurement. ROC curve analysis using dichotomized radiological response (P/S vs R) as classification variables showed AUC = 0.88 (95%CI: 0.77-0.95) for ΔFEV1%pred (optimal cut-off value: +7%, sensitivity: 83%, specificity: 82%, PPV: 73%, NPV: 89%) and AUC = 0.86 (95%CI: 0.75-0.94) for ΔFVC%pred (optimal cut-off value: +6%, sensitivity: 82%, specificity: 74%, PPV: 64%, NPV: 88%).

Conclusions: Dynamic lung volumes and radiological changes after chemotherapy seem directly related. Lung function changes could be an additional tool to better evaluate the response to chemotherapy in MPM.
Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion for malignant pleural tumours: perioperative management and clinical experience. M. Ried, T. Potzger, N. Braune, et al. 2013;43(4):801-7. PubMed · Publisher

Abstract

Objectives: A combination of cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion (HITHOC) was performed for the treatment of primary and secondary pleural malignancies. We describe the perioperative management and our clinical experience.

Methods: Between September 2008 and August 2011, eight patients with pleural manifestation of thymoma (Masaoka stage IVa) and eight patients with malignant pleural mesothelioma (MPM) were prospectively enrolled. Postoperative morbidity, recurrence and survival rates were analysed.

Results: All the patients received multimodality therapy, including chemotherapy, radiation and surgical resection (pleurectomy/decortication) followed by the HITHOC procedure. Chemotherapy perfusion was performed with cisplatin (100-150 mg/m(2)) at 42°C for 1 h. Severe chemotherapy-related complications were not observed. Reoperation was necessary in two patients. There was no 30-day mortality. The median stay on the intensive care unit was 1 day, and the median duration of hospitalization was 15 days. Pleural recurrence of thymoma was evident in one thymoma patient 6 months after HITHOC. At mean follow-up of 22 months, seven thymoma patients (7/8; 88%) are alive without recurrence. Tumour progression was present in six mesothelioma patients (6/8; 75%). Four patients (50%) with MPM are alive, including two with no evidence of mesothelioma, and the median survival is 18 months.

Conclusions: Cytoreductive surgery in combination with HITHOC can be performed with acceptable morbidity and mortality rates in selected patients. Patients should be evaluated by an interdisciplinary team to determine their eligibility for this therapeutic alternative. Early clinical results may encourage the use of this surgical option to provide better local tumour control in a multimodality treatment setting.
Factors predicting poor survival after lung-sparing radical pleurectomy of IMIG stage III malignant pleural mesothelioma. S. Bölükbas, M. Eberlein, N. Kudelin, et al. 2013;44(1):119-23. PubMed · Publisher

Abstract

Objectives: The role of radical pleurectomy (RP) in the management of IMIG stage III in malignant pleural mesothelioma (MPM) remains controversial. The aim of the study was to investigate the feasibility and outcome as well as to determine factors predicting poor survival.

Methods: Patients having IMIG stage III MPM were identified within a prospective multimodality treatment study (RP followed by chemoradiation) between 2002 and 2010 at a single institution. Kaplan-Meier analyses, log-rank test and Cox regression analyses were used to estimate survival and to determine predictors of survival.

Results: A total of 78 patients (66.3 ± 2.5 years, 65 males) underwent RP followed by chemoradiation. A total of 42 (54%) had IMIG stage III. Mortality and morbidity were 4.8 and 31%, respectively. Median survival and 5-year survival were 21 months and 28%, respectively, for stage III patients. Progression-free survival was 11 months. The sites of failure were predominantly locoregional (20/42, 47.6%). Pathological detection of tumour spread at the resected thoracoscopy incisions (median survival 12 vs 35 months, P < 0.001), incomplete resections (median survival 13 vs 35 months, P = 0.01) and male gender (median survival 18 vs 68 months, P < 0.039) were associated with inferior survival in the univariate analyses. Histology, lymph node metastases, laterality and age had no significant impact on survival. The tumour spread at the resected previous incisions remained the only significant prognostic factor (hazard ratio (HR) = 4.3; P = 0.027) in the multivariate analysis. Patients having tumour spread had survival comparable to that of patients at stage IV in the complete patient cohort (median survival 12 vs 8 months; P = 0.39).

Conclusions: Lung-sparing RP for IMIG stage III MPM is feasible and offers promising long-term survival. The tumour spread at the resected previous incisions is associated with more incomplete resections and was a negative prognosticator for long-term survival. The tumour spread at the resected previous incisions or chest tube sites should be considered as T4 or stage IV according to the IMIG staging system.
Lung-sparing total pleurectomy: the surgical option of choice in malignant pleural mesothelioma?. D.A. Waller. 2013;44(1):123-4. Comment PubMed · Publisher
Serum concentration of integrin-linked kinase in malignant pleural mesothelioma and after asbestos exposure. S.B. Watzka, F. Posch, H.I. Pass, et al. 2013;43(5):940-5. PubMed · Publisher · Free full text

Abstract

Objectives: Integrin-linked kinase (ILK) is an intracellular protein implicated in chronic inflammation and neoplastic transformation. In a recently accomplished pilot study, we showed that ILK can be detected in the serum of patients with benign and malignant chest diseases, including malignant pleural mesothelioma (MPM). Interestingly, average serum ILK concentrations were 10 times higher in MPM patients when compared with the rest of the study population, and a diagnostic test solely based on serum ILK concentration could discriminate between MPM and non-MPM with considerable accuracy. This study aimed to investigate whether serum ILK concentration could also be used to discriminate between MPM and asbestos exposure only.

Methods: Using a self-developed sandwich enzyme-linked immunosorbent assay, we measured serum ILK concentrations in 101 MPM patients, and 96 asbestos-exposed, but healthy insulation workers. Seventy-three MPM patients had an epitheloid subtype (72.3%), and 42 had a Stage I or II disease (41.6%).

Results: When compared with asbestos-exposed individuals, MPM patients of all clinical stages had significantly higher (mean ± standard deviation, median) serum ILK concentrations (10.7 ± 13.6, median 7 ng/ml vs 3.1 ± 4.6, median 1.4 ng/ml; P < 0.001). Among MPM patients, the serum ILK concentration was significantly higher at advanced disease stages III + IV than at early stages I + II (13.7 ± 15.9, median 8.5 ng/ml vs 6.7 ± 7.8, median 3.5 ng/ml; P = 0.02). Using serum ILK to discriminate between MPM patients and asbestos-exposed individuals yielded an area under the curve of 0.69 (95% confidence interval 0.63-0.76). The corresponding sensitivity and specificity for a cut-off of 4.49 ng/ml ILK are 61.4 and 80.2%, respectively.

Conclusions: These data show significant differences between MPM patients and asbestos-exposed but healthy individuals concerning their serum ILK concentration. Furthermore, since ILK levels are increased in advanced MPM stages in comparison with early MPM stages, we suggest evaluating its potential use as a marker of disease progression in MPM.
Thoracic shaping technique to avoid residual space after extended pleurectomy/decortication. S. Bölükbas, M. Eberlein, J. Schirren. 2013;44(3):563-4. Case report PubMed · Publisher

Abstract

Extended pleurectomy/decortication or radical pleurectomy is defined as a lung-sparing surgical procedure for malignant pleural mesothelioma. A significant size mismatch between the thoracic cavity and the reduced size of the remaining lung might occur as a result of multiple resections at different sites and lead to residual thoracic space. Residual thoracic space and significant air leakage might result in postoperative complications. A simple technique of diaphragm reconstruction to avoid the residual thoracic space and to reduce the incidence of postoperative complications is described.
Cyberknife radiosurgery for focal paravertebral recurrence after radical pleurectomy/decortication in malignant pleural mesothelioma. L. Lang-Lazdunski, S. Barrington, A. Bille, et al. 2012;41(6):1393-4. Case report PubMed · Publisher

Abstract

We present a case of malignant pleural mesothelioma with focal relapse in the Azygos arch region after radical pleurectomy/decortication and adjuvant chemotherapy. Tumour recurrence was successfully treated by Cyberknife radiosurgery (70 Gy in five fractions). Patient remains disease-free at 40 months without any other treatment.
Fluorescence thoracoscopy in the detection of pleural malignancy. O. Pikin, E. Filonenko, D. Mironenko, et al. 2012;41(3):649-52. PubMed · Publisher

Abstract

Objective: Conventional thoracoscopy, routinely performed in patients with pleural diseases, is not always conclusive in staging of pleural spread. Fluorescence diagnosis (FD) with 5-aminolaevulinic acid (5-ALA) has been used in the diagnostic purpose for various malignancies. The impact of fluorescence thoracoscopy on diagnosis and staging of pleural malignancies was examined.

Methods: A total of 23 patients with non-conclusive pleural effusions were enrolled in the prospective single-institution trial. Eligible patients were administered 25 mg/kg of 5-ALA ('Alasense', Niopik, Russian Federation) per os 3 h before video-assisted thoracoscopy. After conventional inspection with white light, thorough fluorescence investigation of the visceral and parietal pleura was performed (D-LIGHT Auto Fluorescent System, Karl Storz, Germany). Biopsy specimens of both normal and abnormal sites, as determined from white-light and FD inspection, were obtained for histological examination.

Results: There was no morbidity or mortality due to the procedure. A definitive diagnosis was obtained in all cases: malignant mesothelioma in 13 cases, other malignancies (pleural metastases) in 8 cases and non-specific inflammation in 3 patients. A total of 118 biopsy specimens were available for histological examination. In 20 patients, all pleural deposits (n = 60) detected by white-light thoracoscopy had bright red fluorescence during FD and were proved to be malignant. Upstaging occurred in 12 patients (57.2%) (unsuspected 21 tumour deposits) due to FD examination. Micrometastases of macroscopically normal pleura were detected, only by FD, in one patient. Comparing the results of histological examination of specimens detected by conventional thoracoscopy with that by fluorescence thoracoscopy, we obtained 82 true positive, 10 false-negative, 23 true negative, 3 false-positive results with a specificity of 88.4%, sensitivity of 89.1% and diagnostic accuracy of 88.9%.

Conclusions: FD using 5-ALA in the pleural cavity is a feasible diagnostic tool when used in addition to white-light thoracoscopy. It improves visualization of additional lesions or even micrometastases in patients with pleural malignancy.
Long-term survival after lung-sparing total pleurectomy for locally advanced (International Mesothelioma Interest Group Stage T3-T4) non-sarcomatoid malignant pleural mesothelioma. A. Nakas, E. von Meyenfeldt, K. Lau, et al. 2012;41(5):1031-6. PubMed · Publisher

Abstract

Objectives: There is a body of opinion that advocates extrapleural pneumonectomy (EPP) as the only radical treatment option for locally advanced (T3/T4) malignant pleural mesothelioma (MPM). We tested the hypothesis that lung-sparing total pleurectomy (LSTP) can be as effective as EPP in locally advanced MPM with reduced risk.

Methods: We analysed prospective data on 165 patients (128 with epithelioid and 37 with biphasic MPM) with pT3 (n = 108) and pT4 (n = 57) tumours. Ninety-eight (59.4%) of the patients underwent EPP and 67 (40.6%) LSTP. We compared intergroup differences in: length of stay (LOS), post-operative complications, survival, pattern of disease progression and disease-free interval (DFI).

Results: There were significantly more complications after EPP: 67 (68%) vs. 29 (43%) in LSTP, P = 0.002. Thirty-day mortality was 7% for EPP and 3% for LSTP (P = 0.31). LOS was similar (mean 19 days for EPP, 15 days for LSTP, P = 0.19). We noted only minor differences in the initial site of disease progression. In 33 (41%) of EPP patients, disease progressed locally compared with 22 (44%) after LSTP. Seventeen patients post-EPP (21%) had distal progression compared with only three (6%) post-LSTP and synchronous distal and local recurrence was similar: 15 (19%) post-EPP vs. 12% for LSTP (P = 0.11). There was no significant intergroup difference in median survival: EPP 14.7 months (SE 1.3, 95% CI 12.2-17.2) vs. LSTP 13.4 months (SE 1.9, 95% CI 9.7-17.1), P = 0.91, nor in DFI: EPP 10.7 months (SE 0.8, 95% CI 9-12) vs. LSTP 16 months (SE 1, 95% CI 9-22). In chemonaive patients (n = 124), adjuvant chemotherapy was received by significantly more patients after LSTP (32/53 LSTP vs. 26/71 EPP patients, P = 0.011). Estimated 1-5 years survival for EPP was 58, 30, 11, 9 and 6% and for LSTP 52, 28, 20, 13 and 4%.

Conclusions: In disagreement with standard opinion, we advocate LSTP as the procedure of choice in locally advanced MPM: it offers at least equally as good oncological results as EPP in this group of patients with reduced early complications. Despite a tendency for increased local recurrence in the LSTP group, overall survival is not compromised.
Photodynamic drug delivery enhancement in tumours does not depend on leukocyte-endothelial interaction in a human mesothelioma xenograft model. Y. Wang, J.Y. Perentes, S.C. Schäfer, et al. 2012;42(2):348-54. PubMed · Publisher

Abstract

Objectives: The pre-treatment of tumour neovessels by low-level photodynamic therapy (PDT) improves the distribution of concomitantly administered systemic chemotherapy. The mechanism by which PDT permeabilizes the tumour vessel wall is only partially known. We have recently shown that leukocyte-endothelial cell interaction is essential for photodynamic drug delivery to normal tissue. The present study investigates whether PDT enhances drug delivery in malignant mesothelioma and whether it involves comparable mechanisms of actions.

Methods: Human mesothelioma xenografts (H-meso-1) were grown in the dorsal skinfold chambers of 28 nude mice. By intravital microscopy, the rolling and recruitment of leukocytes were assessed in tumour vessels following PDT (Visudyne(®) 400 μg/kg, fluence rate 200 mW/cm(2) and fluence 60 J/cm(2)) using intravital microscopy. Likewise, the distribution of fluorescently labelled macromolecular dextran (FITC-dextran, MW 2000 kDa) was determined after PDT. Study groups included no PDT, PDT, PDT plus a functionally blocking anti-pan-selectin antibody cocktail and PDT plus isotype control antibody.

Results: PDT significantly enhanced the extravascular accumulation of FITC-dextran in mesothelioma xenografts, but not in normal tissue. PDT significantly increased leukocyte-endothelial cell interaction in tumour. While PDT-induced leukocyte recruitment was significantly blunted by the anti-pan-selectin antibodies in the tumour xenograft, this manipulation did not affect the PDT-induced extravasation of FITC-dextran.

Conclusions: Low-level PDT pre-treatment selectively enhances the uptake of systemically circulating macromolecular drugs in malignant mesothelioma, but not in normal tissue. Leukocyte-endothelial cell interaction is not required for PDT-induced drug delivery to malignant mesothelioma.
Single site venovenous extracorporeal membrane oxygenation as an alternative to invasive ventilation in post-pneumonectomy fistula with acute respiratory failure. M. Fica, F. Suárez, R. Aparicio, et al. 2012;41(4):950-2. Case report PubMed · Publisher

Abstract

We report the use of venovenous extracorporeal membrane oxygenation with a single dual lumen cannula in a 42-year-old patient suffering from a post-pneumonectomy fistula and severe respiratory insufficiency, avoiding the classical approach of invasive mechanical ventilation. We discussed the potential advantages of extracorporeal oxygenation as the main support in this particular clinical setting.
The new case for cervical mediastinoscopy in selection for radical surgery for malignant pleural mesothelioma. A. Nakas, D. Waller, K. Lau, et al. 2012;42(1):72-6; discussion 76. PubMed · Publisher

Abstract

Objectives: Selection criteria for radical surgery in malignant pleural mesothelioma (MPM) and related clinical trials remain controversial. The relative importance of nodal metastases and the need for pre-operative nodal staging are undetermined.

Methods: From a prospective database, we identified 212 patients with non-sarcomatoid MPM (160 epithelioid and 52 biphasic). A total of 127 patients underwent extrapleural pneumonectoctomy (EPP) and 85 lung-sparing total pleurectomy (LSTP) with lymphadenectomy. We investigated the effect of nodal burden and distribution in survival by testing for differences between N0, N1 and N2 disease and constructing a theoretical model dividing the patients into four groups according to diseased nodes identified in the surgical specimen: Group 0, no nodal disease; Group CM, nodes accessible by cervical mediastinoscopy (CM): Stations 2, 3a, 4 and 7; Group EBUS/EUS, nodes accessible by endobronchial (EBUS) or endoscopic (EUS) ultrasound: Stations 2, 3a, 4 and 7-11. Group EM, extramediastinal nodes not accessible by CM or EBUS/EUS: Stations 5, 6, internal mammary, pericardial and diaphragmatic lymph nodes.

Results: There was no difference in overall median survival between EPP and LSTP [15.6, SE 1.8, 95% confidence interval (CI) 12-19 months versus 13.4, SE 2.3, 95% CI 9-18 months, P=0.41]. Patients with N0 disease (n=94) had the best prognosis: median survival was 19.6 months (SE 3, 95% CI 13.2-26) versus 12 months for the 19 patients with N1 (SE 1.5, 95% CI 9-15) and 13.6 months for 99 patients with N2 (SE 1.7, 95% CI 10-17), P=0.015. Subgroup analysis of patients with nodal metastases revealed no significant survival difference between group CM and group EBUS/EUS: achieving maximum theoretical diagnostic yield CM could detect 63 (54%) of patients with nodal disease and the median survival of this group was 13.6 months (SE 2, 95% CI 9.6-17.6). EBUS/EUS could detect an additional 30 cases (26%) with survival of 11.3 months (SE 1, 95% CI 9-13.6). The survival in group EM (25 cases, 21%, median survival 18.7 months, SE 6, 95% CI 7-30) was significantly better than groups CM or EBUS/EUS, P=0.002.

Conclusions: There is a strong case for routine CM as a method of prognostic staging in all patients undergoing radical surgery for MPM. The addition of EUS staging and the detection of nodal metastases inaccessible to mediastinoscopy had no prognostic benefit.
Clinical and pathological features of three-year survivors of malignant pleural mesothelioma following extrapleural pneumonectomy. D.J. Sugarbaker, A.S. Wolf, L.R. Chirieac, et al. 2011;40(2):298-303. PubMed · Publisher

Abstract

Objective: Surgery-based multimodality therapy is associated with long-term survival in a significant number of pleural mesothelioma patients. We explored factors associated with 3-year survival in patients with malignant pleural mesothelioma, who underwent extrapleural pneumonectomy, to help refine patient selection criteria for surgery and other therapies.

Methods: With Institutional Review Board approval, we reviewed records in the International Mesothelioma Program Patient Data Registry to identify all patients, who underwent extrapleural pneumonectomy for malignant pleural mesothelioma between 1 January 1988 and 31 May 2007. Vital status as of 31 May 2010 was confirmed. Fisher's exact test was used to compare dichotomous variables for patients who survived at least 3 years with those who did not. Kaplan-Meier analysis was used to estimate the cumulative survival probability for all 3-year survivors.

Results: Among 636 patients who underwent extrapleural pneumonectomy, 117 (18%) survived at least 3 years following surgery, including 26 remaining alive and four lost to follow-up. Of the 3-year survivors, 39 (33%) were female, 61 (52%) had left-sided disease, and the median age was 56 years (range 27-77). Relatively more 3-year survivors were younger than, or at the median age (p=0.0005), or female (p=0.0007), had epithelial tumor histology (p<0.0001) and/or had normal white blood cell count (p=0.0001), hemoglobin (p<0.0001), or platelet count (p<0.0001) preoperatively. The median survival of the 117 patients who survived 3-years was 59 months. Among these patients, a significant association between age and survival was found only for women.

Conclusions: A significant proportion of patients undergoing extrapleural pneumonectomy for pleural mesothelioma experienced extended survival. Although favorable prognostic features were more common, the cohort of 3-year survivors included a substantial number of patients with late-stage disease. The longest survival (median greater than 7 years) was experienced by women under the median age of 56 years. These data support the role of macroscopic cytoreduction through extrapleural pneumonectomy in the context of multimodality therapy to extend survival for malignant pleural mesothelioma. Further efforts to treat micrometastatic disease and improve patient selection are warranted.

Copyright © 2011. Published by Elsevier B.V.
How successful is lung-preserving radical surgery in the mesothelioma and radical surgery-trial environment? A case-controlled analysis. Y. Shahin, J. Wellham, R. Jappie, et al. 2011;39(3):360-3. PubMed · Publisher

Abstract

Objective: To determine whether there is a survival benefit from open-lung-preserving surgery (radical decortication) for malignant mesothelioma, when compared with the non-radical approach in the mesothelioma and radical surgery (MARS)-trial era.

Methods: We compared outcomes between 13 patients with malignant mesothelioma, who underwent radical decortication (group RD, n = 13) with 13 case-matched patients, who had palliative surgery (group non-radical decortication (NRD), n = 13) over a period of 2 years from June 2006 onwards. Patients were matched for age, sex, histology, computed tomography (CT) stage, haematological indices, body mass index (BMI) and adjuvant chemotherapy. We compared perioperative and postoperative courses and long-term survival.

Results: Histology was 25% biphasic and 75% epithelioid in both the groups. There was no significant difference in the proportions receiving adjuvant chemotherapy (54%, p = 1.00), but more patients in the RD group received adjuvant radiotherapy (46% vs 15%, p = 0.20). Median survival was higher for all cell types in the RD group (16.9 months vs 6.8 months, p = 0.001).

Conclusion: Radical open-lung-sparing surgery may confer a survival advantage to patients with malignant mesothelioma, who are fit to undergo radical decortication followed by chemotherapy and radiotherapy. Trials of radical surgery versus no surgery should include lung-sparing operations.

Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Integrin-linked kinase, phosphorylated AKT and the prognosis of malignant pleural mesothelioma. S.B. Watzka, U. Setinek, E.B. Stubenberger, et al. 2011;39(2):180-4. PubMed · Publisher

Abstract

Objective: Integrin-linked kinase (ILK) is a cell membrane-bound molecule implicated in the metastatic progression of many tumour types. It phosphorylates the downstream target AKT (phosphorylated AKT, pAKT), and, by doing this, it activates anti-apoptotic pathways. We have recently shown ILK expression in malignant pleural mesothelioma (MPM). To determine whether ILK expression in MPM is connected with pAKT expression, and whether ILK and pAKT expression have any influence on the patient's prognosis, we correlated ILK and pAKT expression, as assessed by immunohistochemistry, with disease-related survival in a retrospective cohort of 80 MPM patients.

Material And Methods: The paraffin specimens of 80 MPM cases treated from 1990 to 2006 (52 surgical cases, 28 conservative cases) have been retrieved from the archive. The median (range) patients' age was 62 (28-83 years) years; the male-to-female ratio was 3:1. Fifty percent of the patients had an epitheloid subtype. The samples have been stained with anti-ILK as well as with anti-pAKT and scored by two independent pathologists. Intensity of ILK and pAKT expression has been correlated with disease-related survival.

Results: In total, 73 of 80 (91%) MPM samples expressed ILK; 65 of 74 (88%) MPM samples expressed pAKT. Comparing the 5-year disease-related survival according to ILK or pAKT expression, no statistically significant difference could be found between ILK and pAKT expressing or non-expressing patients. However, in the subgroup of conservatively treated MPM patients, those with strong ILK expression had a longer 5-year disease-related survival (p < 0.0001). In total, the only prognostic factor across all ILK, pAKT and therapy subgroups was the histological subtype (p = 0.01). The prognostic significance of the histological subtype has been confirmed in multivariate analysis (p = 0.005).

Conclusion: The expression of ILK in MPM is connected with the expression of the downstream target pAKT, but neither ILK nor pAKT expression has a measurable influence on the patient's prognosis, except for certain subgroups of MPM. However, to shed light on the true prognostic impact of ILK and pAKT expression in MPM, prospective trials are needed.

Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Malignant pericardial mesothelioma. M. Sakuraba, T. Tatsumori, M. Hirama, et al. 2011;39(3):420. Case report PubMed · Publisher
Malignant pleural mesothelioma with osteosarcomatous differentiation: characteristic bone scintigraphy findings associated with enhanced tumorous osteogenesis. M. Nakao, T. Hishida, G. Ishii, et al. 2011;39(3):421. Case report PubMed · Publisher
Staging malignant pleural mesothelioma: additional investigation may not improve accuracy. D.G. West, W.S. Walker. 2011;39(5):800; author reply 800-1. Letter · Comment PubMed · Publisher
A new technique of diaphragmatic patch fixation in extrapleural pneumonectomy. M. Schiavon, A. De Filippis, G. Marulli, et al. 2010;38(6):798-800. PubMed · Publisher

Abstract

Extrapleural pneumonectomy (EPP) is an established surgical treatment for malignant mesothelioma; this operation is, however, burdened by a high rate of perioperative morbidity, mostly related to the surgical procedure. Diaphragmatic patch dehiscence is a potentially serious complication often related to the difficulty in placement of the fixing stitches, especially in the costo-phrenic angle. We present our experience with the use of titanium-plate support for an easy and safe positioning of the diaphragmatic patch.

Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Awake video-assisted pleural decortication for empyema thoracis. F. Tacconi, E. Pompeo, E. Fabbi, et al. 2010;37(3):594-601. PubMed · Publisher

Abstract

Objective: To evaluate feasibility, technical features and results of video-assisted pleural decortication for empyema thoracis performed in awake patients.

Methods: This retrospective analysis involved a cohort of 19 patients (median age: 58 years) undergoing awake video-assisted thoracoscopic pleural decortication under epidural anaesthesia (N=15) or paravertebral blocks (N=4) between March 2004 and September 2008. Baseline and perioperative data including degree of postoperative lung re-expansion at 48 h, hospital stay, morbidity rate and daily fluid loss were recorded. In addition, intra- and perioperative changes in main pathophysiological variables PaO(2)/FiO(2) ratio, PaCO(2), mean arterial pressure and heart rate were analysed.

Results: Origin of the empyema was parapneumonic (N=14), post-traumatic (N=3) and cancer related (N=2). All patients underwent previous conservative management. The duration of the symptoms averaged 35 days (quartile range (QR): 28-40). Co-morbidities included chronic obstructive pulmonary disease (COPD) (N=4), HIV infection (N=1), diabetes mellitus (N=2) and cirrhosis (N=1). Operation was performed videothoracospically in 15 patients whereas four patients with major pleural thickening underwent awake lateral thoracotomy. Operative time averaged 50 min (QR: 40-70). Perioperative data analysis showed no intra-operative deterioration in arterial oxygenation (median-Delta: 0 mm Hg, QR: -5/+9, P=0.6). Transient permissive hypercapnia (<55 mm Hg) developed in three patients with no need of conversion to general anaesthesia. Median pain level assessed by a visual analogue score (VAS) 1h postoperatively was 4 (QR: 2-5), and it was significantly reduced on postoperative day 1 (median 3, QR: 2-4, P=0.03). There was neither mortality nor major morbidity. Hospitalisation averaged 6 days (QR: 5-7). At postoperative chest X-ray, lung re-expansion was rated as complete in 16 patients, satisfactory in (>80%) two patients and unsatisfactory in a 86-year-old patient with pleural mesothelioma who has the chest drain still in place 5 months after surgery. No patient had recurrence of the empyema at subsequent follow-ups.

Conclusions: In our study, awake video-assisted pleural decortication proved feasible and resulted in satisfactory lung re-expansion in 95% of the patients. We hypothesise that spontaneous ventilation facilitated both identification of the correct plane and dissection, thus resulting in lesser surgical injury on the underlying lung.

Copyright (c) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Editorial comment May cyclooxygenase-2 (COX-2), p21 and p27 expression affect prognosis and therapeutic strategy of patients with malignant pleural mesothelioma?. I. Opitz. 2010;38(3):252-3. Comment · Editorial PubMed · Publisher
Effect of induction chemotherapy on lung function and exercise capacity in patients affected by malignant pleural mesothelioma. G. Marulli, F. Rea, S. Nicotra, et al. 2010;37(6):1464-9. PubMed · Publisher

Abstract

Objectives: The effect of induction chemotherapy (IC) on lung function and exercise capacity in patients with malignant pleural mesothelioma (MPM) has not been largely examined. The aim of this study was to evaluate the changes in pulmonary function and oxygen consumption following IC in patients with MPM.

Methods: Between 2004 and 2009, 36 consecutive patients (mean age 62.1 + or - 1.5 years, M/F = 25/11) were prospectively investigated. Data concerning medical history, histology, staging and response to chemotherapy were collected. All patients underwent pulmonary function test before (in the absence of pleural effusion) and after chemotherapy (platinum-based agent plus pemetrexed); 23 out of 36 patients also performed a cardiopulmonary incremental exercise test.

Results: An epithelioid histotype was documented in 88.8% of patients. A partial response to chemotherapy was observed in 44.5% of cases and 36.1% of patients experienced grade 2-3 toxicity. A significant improvement in forced expiratory volume in 1s (FEV(1)) (0.13 + or - 0.30 l; P = 0.01), in VO(2) peak (1.76 + or - 2.91 ml kg(-1) min(-1); P = 0.005), in PaO(2) at rest (4.76 + or - 9.84 mmHg; P = 0.03) and in PaO(2) at peak exercise (6.26 + or - 12.72 mmHg; P = 0.04) was detected. The diffusion capacity of the lung for carbon monoxide (DLCO) also increased (1.25 + or - 4.68 ml min(-1) mmHg(-1)), although not significantly (P = 0.20). The stratified analysis based on the response to IC showed a significant improvement in FEV(1), forced vital capacity (FVC) and vital capacity (VC) (both absolute and percentage of predicted values) only in patients with a partial response.

Conclusions: An improvement in lung function and exercise capacity was seen after IC in patients with MPM. These data suggest that IC does not compromise cardiopulmonary performance in this subset of patients.

Copyright 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Efficacy of intra-operative unilateral diaphragm plication for patients undergoing unilateral phrenicotomy during extended surgery. T. Tokunaga, N. Sawabata, Y. Kadota, et al. 2010;38(5):600-3. PubMed · Publisher

Abstract

Objective: Diaphragm plication is used to improve lung function and respiratory insufficiency in patients suffering from diaphragm paralysis. We assessed the efficacy of intra-operative unilateral diaphragm plication for prevention of postoperative pulmonary complications in patients, who underwent a phrenicotomy due to extended surgical intervention.

Methods: Intra-operative unilateral diaphragm plication was performed in 13 patients, who underwent a unilateral phrenicotomy during an extended thoracic operation. Six patients had lung cancer, six had a mediastinal tumour and one had a mesothelioma. We retrospectively observed the postoperative clinical courses in the perioperative period and lung function results at 1 year after operation. The postoperative lung function was compared with the predicted postoperative lung function. In addition, we observed clinical symptoms and radiological findings of the follow-up period.

Results: Ten (77%) of the cases revealed no postoperative complications, while three (23%) had pulmonary complications and two (15%) required prolonged mechanical ventilation. Diaphragm paralysis was not shown clinically and radiologically during the follow-up period. Postoperative lung function was similar to predicted postoperative lung function.

Conclusion: Unilateral diaphragm plication in a patient undergoing a unilateral phrenicotomy during an extended thoracic operation is effective to prevent postoperative pulmonary complications and to preserve postoperative lung function.

Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Managing the pneumonectomy space after extrapleural pneumonectomy: postoperative intrathoracic pressure monitoring. A.S. Wolf, F.L. Jacobson, T.R. Tilleman, et al. 2010;37(4):770-5. PubMed · Publisher

Abstract

Objective: Rapid fluid evacuation of the pneumonectomy space can cause ipsilateral mediastinal shift, contralateral lung hyperexpansion, compromised caval blood return and a precipitous drop in cardiac output. Conversely, rapid fluid accumulation can cause contralateral mediastinal shift with compression of the remaining lung and respiratory insufficiency. In this retrospective analysis, we evaluate the efficacy of intrathoracic pressure monitoring and intermittent fluid aspiration to manage the pneumonectomy space in the early postoperative period following extrapleural pneumonectomy.

Methods: Prior to chest closure, a 14 F Rob-Nel catheter was placed in the pneumonectomy space and connected to pressure tubing to monitor ipsilateral intrathoracic pressure continuously. Central venous pressure monitoring and serial chest X-rays were performed according to usual intensive care routine. Pneumonectomy space fluid was aspirated intermittently when there was increase in intrathoracic pressure, refractory hypotension, mediastinal shift on chest X-ray, or clinical decline. Postoperative imaging was re-evaluated retrospectively for confirmation of mediastinal shift by a senior radiologist.

Results: From January to December 2008, 47 patients underwent extrapleural pneumonectomy for pleural mesothelioma (median age 65 years with range 34-79 years, 77% male). Twenty (43%) patients had left-sided disease and 32 (68%) received local heated intra-operative cisplatin-based chemotherapy. The median baseline pneumonectomy space pressure was 3 cm H(2)O (range: -6 to +12). The median amount of fluid withdrawn over the first 2 days postoperatively was 300 cc (range: 0-1980 cc). Thirty-one (69%) patients had minimal, if any, change in mediastinal position during the first 2 postoperative days with intermittent drainage performed when the pneumonectomy space pressure rose. Eleven (25%) patients had increasing contralateral shift, four of whom had return of the mediastinum to baseline during this time period. The median fluid drained from the four patients whose contralateral shift resolved was 290 cc (range: 220-800 cc) compared to 200 cc (range: 150-480 cc) from the seven patients whose contralateral shift remained, but this difference did not reach significance (p=0.365).

Conclusions: Intrathoracic pressure monitoring may be used as a guide for intermittent fluid evacuation of the pneumonectomy space prior to onset of clinical signs or symptoms, to avoid the cardiopulmonary risks of rapid fluid removal. Contralateral mediastinal shift should be treated with incremental drainage when there is a rise in intrathoracic pressure to prevent cardiovascular complications.

Copyright (c) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
May cyclooxygenase-2 (COX-2), p21 and p27 expression affect prognosis and therapeutic strategy of patients with malignant pleural mesothelioma?. T.C. Mineo, V. Ambrogi, M.E. Cufari, et al. 2010;38(3):245-52. PubMed · Publisher

Abstract

Objectives: The expression of cyclooxygenase-2 (COX-2) and cell-cycle proteins (p21 and p27) proves useful in predicting prognosis and orientating therapy in many malignant tumours. Malignant pleural mesothelioma is an uncommon and lethal cancer for which there are limited treatment options. In this study, we evaluated the impact on prognosis and the influence on therapeutic strategy of immunohistochemical expression of COX-2, p21 and p27 in specimens from patients treated for malignant pleural mesothelioma.

Methods: We retrospectively reviewed immunohistochemical expression of COX-2, p21 and p27 dichotomised into high and low expression from specimens of 77 consecutive patients undergoing biopsy-plus-pleurodesis (n=6), pleurectomy-decortication (n=44) or extrapleural pneumonectomy (n=27) operations for malignant pleural mesothelioma between 1987 and 2007. Histology was of epithelioid (n=50), biphasic (n=17) and sarcomatoid (n=10) subtypes. Tumour node metastasis (TNM)-stage was I (n=21), II (n=36) and III (n=20). Therapies used were sole adjuvant radiotherapy (n=17), adjuvant radio-chemotherapy (n=56) and neo-adjuvant chemotherapy plus adjuvant radiotherapy (n=4). From 2005 on, preoperative maximal standard uptake value (SUV(MAX)) was also measured by fluorodeoxyglucose positron-emission-tomography. Significance was investigated by Kaplan-Meier survival and Cox regression analysis.

Results: The median survival was 10 months. Survival was negatively influenced by histology (epithelioid vs biphasic vs sarcomatoid) (p=0.009), positive macroscopic resection margins (p=0.016), metastatic mediastinal lymph nodes (p=0.016), high COX-2 (p=0.0001) expression, low p21 (p=0.0001) expression and low p27 (p=0.001) expression. Conversely, neither the type of surgery (biopsy-plus-pleurodesis vs pleurectomy-decortication vs extrapleural pneumonectomy), nor preoperative SUV(MAX) (> or = 6.0 vs <6.0), or combined therapies (sole radiotherapy vs adjuvant radio-chemotherapy vs neo-adjuvant chemotherapy plus adjuvant radiotherapy) reached a significant level of difference. Cox regression analysis showed that only immunohistochemical triple combination of high COX-2 and low p21 and p27 expression influenced survival (p=0.0001, hazard ratio 4.7, 95% confidence intervals 3-11) regardless of type of treatment.

Conclusions: At Cox regression analysis, a combination of high COX-2 and low p21 and p27 expression resulted in the only negative prognosticator of malignant pleural mesothelioma. With this combination, less aggressive surgical options might be preferred.

Copyright 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Non-Hodgkin's lymphoma presenting as an isolated soft-tissue chest wall mass. P. Peters, N. Butler, J. Mundy, et al. 2010;37(2):487. Case report PubMed · Publisher
Obtaining an upper estimate of the survival benefit associated with surgery for mesothelioma. M. Utley, F. Fiorentino, T. Treasure. 2010;38(3):241-4. PubMed · Publisher

Abstract

Objective: This study aimed to obtain an upper estimate of any survival benefit conferred by resection in patients with a diagnosis of malignant pleural mesothelioma.

Methods: We analysed published data concerning survival from diagnosis among four groups of patients with mesothelioma, identified by ascending level of intervention: (A) no surgery; (B) thoracotomy but no resection; (C) resection but no adjuvant treatment; and (D) resection as part of multimodality treatment. Mean survival was estimated for each of these four groups. Mean survival was also estimated for all those having resection (groups C and D) and for all those not having a resection (groups A and B).

Results: Mean survival was 16.8, 17.8 and 17 months for those having no surgery, thoracotomy alone and resection with no adjuvant treatment respectively (groups A, B and C) and 32.9 months for those having multimodality treatment (group D). Mean survival was 25.6 months in those who had resection and 17.1 months in those that did not. The survival advantage of any management that included surgical resection was estimated as being no more than 9 months. This is the most optimistic estimate and requires all observed differences in survival to be attributed to the effect of treatment and none to selection for treatment. Furthermore, within this upper estimate is included any benefit from other components of multimodality treatment.

Conclusions: Given the burden of morbidity of resection in the management of pleural mesothelioma, this most optimistic estimate of the magnitude of any survival benefit should be taken into account in any policy decision, in clinical trial proposals and in strategies adopted by clinical teams.

Copyright 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Outcome of patients with nonspecific pleuritis/fibrosis on thoracoscopic pleural biopsies. H.E. Davies, J.E. Nicholson, N.M. Rahman, et al. 2010;38(4):472-7. PubMed · Publisher

Abstract

Objective: Medical thoracoscopy is recommended in the investigation of patients with exudative pleural effusions, especially when pleural fluid analysis is uninformative. The histological finding of 'nonspecific pleuritis/fibrosis' is common in thoracoscopic biopsies and presents a great uncertainty for clinicians and patients as the long-term outcome of these patients is unclear, and anxieties about undiagnosed malignancy persist.

Method: A retrospective case-note study of 142 patients who underwent medical thoracoscopy over a 58-month period in a tertiary referral centre with a high incidence of mesothelioma. Patients with 'nonspecific pleuritis/fibrosis' were followed up until death or for a mean (±SD) period of 21.3 (±12.0) months.

Results: A definitive histological diagnosis was achieved in 98 (69%) patients. A total of 44 (31%) patients had 'nonspecific pleuritis/fibrosis'. Five (12%) were subsequently diagnosed with malignant pleural disease after a mean interval of 9.8 (±4.6) months. All five patients had histologically confirmed mesothelioma. In 26 patients with 'nonspecific pleuritis/fibrosis', no cause for the pleural effusion was discovered. The false-negative rate of thoracoscopic biopsy for the detection of pleural malignancy was 5%, with a diagnostic sensitivity of 95% and negative predictive value of 90%. Pleural effusion recurrence was more frequently associated with a false-negative pleural biopsy result. However, there was no correlation with other patient characteristics or the thoracoscopist's prediction based on macroscopic appearances.

Conclusion: Thoracoscopic pleural biopsy is valuable in the diagnosis of pleural malignancies. Patients with 'nonspecific pleuritis/fibrosis' require follow-up as a malignant diagnosis (especially mesothelioma) may eventually be established in approximately 12% of cases.

Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Prognostic significance of epithelial-mesenchymal transition in malignant pleural mesothelioma. A. Schramm, I. Opitz, S. Thies, et al. 2010;37(3):566-72. PubMed · Publisher

Abstract

Background: Epithelial-to-mesenchymal transition (EMT) is a morphologic transdifferentiation of carcinomas, conferring increased tumour invasiveness, but may also be applied to the epithelioid versus sarcomatoid histotype of malignant pleural mesothelioma (MPM). Herein, we correlated proteins of a putative MPM-EMT axis, including periostin, epidermal growth factor receptor (EGFR), integrin beta1, phosphatase and tensin homologue (PTEN), integrin-linked kinase (ILK), p21 and p27, with clinico-pathologic parameters, in particular overall survival (OS).

Patients And Methods: A retrospective cohort of 352 mostly untreated patients with MPM was investigated by immunohistochemistry of a tissue microarray. Protein expression intensities were semi-quantitatively scored from 0 to 3 in their respective compartments, including peritumoural stroma as well as tumour cell plasma membrane, cytoplasm or nucleus. Data were correlated with histotype and survival outcome.

Results: A total of 32% of the tumours were diagnosed as epithelioid, 13% as sarcomatoid and 55% as biphasic histotype. High expression of membranous EGFR and integrin beta1 as well as nuclear p27 correlated with the epithelioid and high expression of cytoplasmic tumoural and stromal periostin with the sarcomatoid histotype. The median survival time of the 128 patients with complete follow-up data was 11.7 months. Univariate survival analysis revealed age, epithelioid histotype and any therapy as prognosticators for better OS. High expression of cytoplasmic PTEN or ILK as well as high expression of nuclear p21 or p27 correlated with increased, whereas high expression of cytoplasmic periostin with decreased OS (all p values <0.05). Multivariate Cox regression revealed any treatment, low cytoplasmic periostin and high cytoplasmic PTEN as independent prognosticators for better OS.

Conclusion: Activation of periostin-triggered EMT is associated with the sarcomatoid histotype and has an impact on shorter survival of MPM patients. Finally, only the high expression of PTEN and the low expression of cytosolic periostin could be shown to be independent prognostic factors for longer OS.

Copyright (c) 2009. Published by Elsevier B.V.
Surgery for mesothelioma: MARS landing and future missions. T. Treasure. 2010;37(3):509-10. Editorial PubMed · Publisher

Summary

This editorial discussed the first report of the Mesothelioma and Radical Surgery (MARS) trial, a feasibility study testing whether patients with mesothelioma could be randomly allocated to extrapleural pneumonectomy (EPP) or no surgical resection. Patients received either trimodality therapy (chemotherapy, EPP and radical hemithoracic radiotherapy) or the same chemotherapy followed by any appropriate non-surgical treatment. Consent was given in two stages. Of 112 patients who consented to staging and chemotherapy, 57 were reviewed as candidates for randomisation, seven were excluded, and 50 (45%) were randomised. The target of 50 was reached in late 2008. Outcomes were not yet available, and the trial was not powered to show effectiveness. The author explained that earlier claims of longer survival after EPP came from follow-up studies of multimodality therapy that were open to selection bias. He cited later reports: complications in over 60% of patients (Boston); major complications in more than 50% and 3-year survival of 14% (Mayo Clinic); and median survival of 10.2 months with EPP plus intensity-modulated radiotherapy. He noted a growing emphasis on lung-sparing surgery. He discussed whether cure, longer survival or palliation should be the outcome for a future trial. He stated that a planned MARS-2 trial would evaluate total pleurectomy, with respiratory function and quality of life as outcomes. He concluded that MARS showed random allocation was possible, and that "some unbiased evidence is clearly better than none."

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Surgical assessment of malignant pleural mesothelioma: have we reached a critical stage?. A. Nakas, E. Black, J. Entwisle, et al. 2010;37(6):1457-63. PubMed · Publisher

Abstract

Objective: The International Mesothelioma Interest Group (IMIG) classification is the most widely used staging system but is based on post-resectional parameters. We aimed to test the association between clinical and pathological staging and to identify possible discrepancies.

Methods: We identified 164 consecutive patients (144 males and 20 females, with mean age 58 years) who underwent radical surgery (114 extrapleural pneumonectomy; 50 radical pleurectomy/decortication) for malignant pleural mesothelioma (MPM). The patients were clinically staged with CT + or - MRI (CT, computed tomography; MRI, magnetic resonance imaging).

Results: Clinical T (cT) stage proved to be the same as pathological T (pT) stage in 44%; understaged in 46% and overstaged in 10%. Clinical N (cN) stage proved to be the same as pathological N (pN) stage in 56%; understaged in 31% and overstaged in 13%. Disease-free interval (DFI) was associated with cT stage (median DFI 29 months, SE 13, 95% CI 3-54 months for cT1; median 5, SE 3, 95% CI 3-6 months for cT4, p=0.02) but not clinical N stage (median DFI 12 months, SE 1, 95% CI 9-15 months for cN0; median DFI 11 months, SE 0.3, 95% CI 10-12 months for cN2, p=0.5) and was associated with both pT (median DFI 31 months, SE 17, 95% CI 0-64 months for pT1; median DFI 8 months, SE1, 95% CI 6-11 months for pT4, p=0.03) and pN stage (median DFI 14 months, SE 3, 95% CI 9-20 months for pN0; median DFI 10 months, SE 1, 95% CI 8-13 months for pN2, p=0.02). Overall survival was associated with cT stage (median survival 25 months, SE 3, 95% CI 20-30 months for cT1; median survival 11 months, SE 3, 95% CI 10-11 months for cT4, p=0.01) but not cN stage (median survival 15 months, SE 2, 95% CI 11-19 months for cN0; median survival 15 months, SE 2, 95% CI 12-19 months for cN2, p=0.49) and pN stage (median survival 22 months, SE 3, 95% CI 19-27 months for pN0; median survival 14 months, SE 1, 95% CI 12-17 months for pN2, p=0.01) but not pT stage (median survival 27 months, SE 4, 95% CI 19-35 months for pT1; median survival 12 months, SE 2, 95% CI 9-15 months for pT4, p=0.06). Pathological IMIG stage was associated with DFI and overall survival; however, preoperative IMIG stage was less useful.

Conclusions: There are deficiencies in the current staging system for MPM and discrepancies between clinical and pathological systems. Future improvements are needed in clinical descriptors of nodal status and pathological descriptors of T stage. Subsequent IMIG stage grouping also needs revision.

Copyright 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Three decades of experience in the surgical multi-modality management of pleural mesothelioma. H. Luckraz, M. Rahman, N. Patel, et al. 2010;37(3):552-6. PubMed · Publisher

Abstract

Background: Optimal management of diffuse malignant pleural mesothelioma (DMPM) remains unclear. We report our 30-year surgical experience with DMPM with emphasis on surgical procedure and post-operative adjuvant therapy.

Methods: During the period of the study, 217 patients with DMPM were referred for surgical opinion. Patients who only had pleural biopsies were excluded (n=78). Consecutive patients who underwent surgical treatment were included (n=139). Surgical options were extra-pleural pneumonectomy (EPP) for Butchart stage I disease in clinically fit patients (n=49) or pleurectomy/decortication in patients who were either not fit for EPP or had advanced disease (Butchart stage II and III) or both (n=90). Post-operative adjuvant therapy included either chemotherapy, radiotherapy, both or none.

Results: The median follow-up was 10.0 months. The longest survival (median 26.0 months, IQR: 11.14-40.9 months) occurred in the pleurectomy/decortication group who received both post-operative chemotherapy and radiotherapy (n=24) (p<0.001). EPP whether or not combined with adjuvant therapy provided no significant survival advantage in comparison to pleurectomy/decortication (overall median survival 10.3 months vs 10.1 months, p=0.09). On univariate analysis, pleurectomy/decortication combined with chemotherapy and radiotherapy was the strongest predictor of prolonged survival (Hazard Ratio=3.6). Multivariate analysis with the inclusion of histological type, surgical procedure and type of adjuvant therapy, EPP without adjuvant therapy was an independent risk-factor for decreased survival (Hazard Ratio=9.2).

Conclusions: In this series, cytoreductive surgery combined with post-operative adjuvant therapy provided better survival despite either advanced disease or surgically less fit patients. Thus, pleurectomy/decortication may be the procedure of choice, given that neither surgical procedure (EPP or PD) is not curative.

Copyright (c) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

2000s

Outcome after extrapleural pneumonectomy for malignant pleural mesothelioma. C. Aigner, M.A. Hoda, G. Lang, et al. 2008;34(1):204-7. PubMed · Publisher

Abstract

Background: Malignant pleural mesothelioma is a mainly asbestos-related neoplasm that occurs with increasing frequency and is associated with a poor prognosis. Extrapleural pneumonectomy which was initially performed as a stand-alone treatment in patients with resectable disease is now currently almost uniformly applied as part of a multi-modal approach. Its value and advantage over other therapeutic strategies remain points of discussion. We therefore analysed our experience with extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma.

Methods: We retrospectively reviewed our institutional experience with all consecutive patients undergoing extrapleural pneumonectomy for malignant pleural mesothelioma from 1994 to 2005. Patients were analysed with regard to hospital mortality and morbidity and long-term outcome.

Results: Forty-nine patients (10 female/39 male, mean age 58+12 years) underwent extrapleural pneumonectomy during the observation period. Median ICU stay was 1 day, median postoperative length of hospital stay was 13 days. After a mean follow-up of 2573 days, median survival was 376 days (mean 672+121 days, range 9-3384). One-year survival was 53%, 3-year survival 27% and 5-year survival 19%.

Conclusion: Extrapleural pneumonectomy as part of a multi-modality treatment regimen is a good treatment option for selected patients with malignant pleural mesothelioma. The long-term results of this limited series compare favourably to non-surgical treatment regimens. Larger randomised prospective multi-centre trials are warranted to establish clear guidelines.
Pericardial malignant mesothelioma: a latent complication of radiotherapy?. G.R. Small, M. Nicolson, K. Buchan, et al. 2008;33(4):745-7. Case report PubMed · Publisher

Abstract

Pericardial diseases can be difficult to differentiate from myocardial conditions. Diagnosis can be challenging and often requires the use of different imaging modalities. Here, we describe a case which presented with common cardiac symptoms which were shown to be the result of a rare condition. A 62-year-old lady presented with left femoral artery embolism. Post-embolectomy she developed cardiac failure. Three months previously an acellular, sterile pericardial effusion had been drained. In 1993 a left mastectomy and axillary node clearance was performed for breast cancer. Adjuvant chemotherapy and radiotherapy were administered. Examination revealed a raised jugular venous pressure (JVP) with rapid Y descent and Kussmaul's sign. CT chest and abdomen found no recurrence of breast carcinoma. Cardiac MRI demonstrated thickened pericardium. At cardiac catheterisation haemodynamic responses consistent with constrictive pericarditis were seen. Pericardiectomy was performed. Histology revealed pericardial epithelioid malignant mesothelioma. 18-FDG-PET CT post-operatively was negative in the pericardium and pleura. Chemotherapy with pemetrexed and carboplatin was given. The patient died 9 months after presentation. Radiotherapy and asbestos exposure are both associated with pericardial mesothelioma and the aetiology in this case was not clear. The condition carries a poor prognosis and is invariable fatal although newer chemotherapeutic regimens have prolonged survival times.
Local recurrence model of malignant pleural mesothelioma for investigation of intrapleural treatment. I. Opitz, D. Lardinois, S. Arni, et al. 2007;31(5):773-8. PubMed · Publisher

Abstract

Objective: Local recurrence remains a major problem in the treatment of malignant pleural mesothelioma. The aim of the underlying study was to establish a standardised local recurrence model in rats which enables to study different intrapleural therapies.

Materials And Methods: Fifty microlitre containing 1 x 10(6) cells of a syngeneic rat malignant mesothelioma cell line (II-45), established from mesothelioma in Fischer 344 rats exposed to asbestos, were inoculated subpleurally via a left-sided thoracotomy. Tumour size was assessed 6 days later and the tumour nodule completely resected. Evaluation of recurrence at the resection site was performed after 10 days (n=6) and 6 days (n=6). The recurrent nodule was histopathologically confirmed. In a second experiment, this new recurrence model was evaluated for the effect of intrapleural therapy with different agents: 4 ml of cisplatin-solution (100mg(2)/kg BW), cisplatin combined with the fibrin-based sealant Vivostat, 4 ml taurolidine 2%, repeated injection of 1 microg of the chemokine CCL-19 at the tumour site and 4 ml povidone-iodine in a dilution 1:10. In a control group, the chest cavity was filled with 4 ml 0.9% NaCl. The primary endpoint was the extent of tumour recurrence.

Results: Six days after inoculation, all animals presented a standardised tumour nodule at the injection site of a mean diameter of 5.1 (+/-0.8)mm. Evaluation of the recurrence after 10 days showed a relapse directly at the resection site, but additional tumour nodules on the ipsi- and contralateral chest wall were found and histologically confirmed. The animals that were sacrificed 6 days after resection of the tumour nodule showed a recurrence only at the resection site with no macroscopic or microscopic evidence of other tumour. Resection of the tumour nodule combined with intrapleural application of the different agents lead to clear reduction of recurrence. The strongest effect was observed after intrapleural application of cisplatin-Vivostat with significant decrease of the longest, widest and thickest diameter of the recurrence.

Conclusions: With this new recurrence model for investigation of malignant pleural mesothelioma in rats, we were able to investigate new intrapleural therapies after pneumonectomy. The intrapleural application of cisplatin-Vivostat significantly reduced the extent of local recurrence.
Multimodality approach in management of malignant pleural mesothelioma. S. Neragi-Miandoab. 2006;29(1):14-9. Review PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a solid, locally aggressive tumor, which has been closely linked to asbestos exposure. The survival rate without treatment ranges from 4 to 12 months. Response to chemotherapy and radiation is poor, and surgery is the most effective therapy. There are currently 3000 new MPM cases per year in the United States, with the peak incidence in the United States and Europe expected to occur in the year 2020. The prognosis depends on the stage of the tumor at the time of diagnosis, its histological type, lymph node status, and resection margins. While the diagnosis is often delayed, earlier intervention may improve life expectancy. Single-modality therapy has not been effective in changing the natural history of MPM. As a result, multimodality regimens involving surgery with radiation, chemotherapy, or immunotherapy have been initiated. Multiple modality approach has demonstrated favorable outcome, particularly in patients with epithelial histology, negative resection margins and presence of no metastases to extrapleural lymph nodes. Cisplatin and mitomycin have demonstrated modest efficacy in management of distant tumor recurrence. Cisplatin and gemcitabine regimen as well as cisplatin/pemetrexed followed by 54 Gy of adjuvant hemithorax radiation have been reported to improve the outcome.
Midterm result of leaflet extension technique in aortic regurgitation. H. Ahn, K.H. Kim, Y.J. Kim. 2002;21(3):465-9. PubMed · Publisher

Abstract

Objectives: Aortic valve leaflet extension using glutaraldehyde-fixed autopericardium in aortic regurgitation (AR) is technically demanding, and it is not a popular procedure among surgeons. This study evaluates the effectiveness and clinical feasibility of the leaflet extension technique as a treatment modality for AR.

Materials And Methods: From March 1995 to March 2001, 34 consecutive patients underwent the leaflet extension technique. The mean age of the 26 men and eight women was 31.0+/-14.3 years (range 16-68). They were all diagnosed with pure aortic valve regurgitation, and nine (27.3%) had associated mitral valvular heart diseases. Accurate measurement of the leaflet free margins was performed with a pair of compasses before leaflet extension. Glutaraldehyde-fixed autopericardium was designed according to the free margin lengths. Leaflet extension was performed in three aortic leaflets for 29 patients but only one leaflet was extended in the remaining four. The nine patients with associated mitral valvular heart disease also underwent mitral valvuloplasty. Mean cardiopulmonary bypass time and ischemic time in 25 isolated AR group were 128.7+/-26.5min (range 70--180) and 101.5+/-25.5min (range 41-150), respectively.

Results: There was no incidence of in-hospital mortality. Immediate postoperative echocardiography revealed grade II AR in one, grade I AR in ten and no AR in the remaining 23 patients. Mean follow-up duration was 49.6+/-18.8 months (range 4.1-77.1). Echocardiographic AR grades during follow-up were grade II in 13, grade I in 11 and no AR in eight. The remaining two patients underwent reoperation, one aortic valve replacement because of subacute bacterial endocarditis that occurred 7 months after leaflet extension, and the other Ross operation because of the dehiscence of the valvuloplasty suture site that developed 4 months later (AR associated with Behcet's disease). There was one case of mortality due to malignant mesothelioma 4 years after aortic valvuloplasty. The cumulative survival rate was 94.1% at 5 years. Freedom from reoperation was 93.8% at 1 year and after.

Conclusions: The leaflet extension technique is an acceptable surgical treatment modality for AR and its clinical results were confirmed in this study to be very good. A careful long-term follow-up study will be necessary to evaluate the long-term durability of the glutaraldehyde-preserved autologous pericardium as a leaflet tissue.
Solitary fibrous tumors of the pleura: clinical characteristics, surgical treatment and outcome. P. Magdeleinat, M. Alifano, A. Petino, et al. 2002;21(6):1087-93. PubMed · Publisher

Abstract

Objective: The aim of this paper is to study clinical characteristics, surgical treatment and outcome of patients with solitary fibrous tumor of the pleura operated in our institutions in a 20-year period.

Methods: Clinical records of all patients operated for solitary fibrous tumors of the pleura between 1981 and 2000 were reviewed retrospectively. Tumors were classified as malignant in the presence of at least one of the following criteria: (1) high mitotic activity; (2) high cellularity with crowding and overlapping of nuclei; (3) presence of necrosis; (4) pleomorphism; otherwise they were considered as benign.

Results: Sixty patients (mean age 55 years) were operated in this period. None had asbestos exposure. Symptoms were present in 31 cases. Surgical approaches included thoracotomy (n=53), video-assisted thoracoscopy (n=6), and median sternotomy (n=1). Tumors originated from visceral pleura in 48 cases, from parietal, mediastinal or diaphragmatic pleura in seven, two and three cases, respectively; their mean diameter was 8.5 cm. Tumors could be resected with their implantation basis in 49 patients. In the remaining 11, extended resections were performed, including lung parenchyma (lobectomy, n=4, pneumonectomy, n=2), osteomuscular chest wall structures (n=2), diaphragm (n=2), and pericardium (n=1). Two postoperative deaths (due to myocardial infarction and pulmonary embolism, respectively) occurred. Tumors were pathologically benign in 38 cases and malignant in 22 cases. Mean follow-up was 88 months. Resection was complete in all the patients with benign tumors and no recurrence occurred. Resection was considered as complete in 21/22 malignant tumors. Local recurrence was observed in two cases. Both could be successfully managed by iterative exeresis (no extended resection had been initially performed). Metastatic disease (responsible for patient's death) was observed following the only incomplete resection. Actuarial 5- and 10-year survival rates were 97% for benign tumors and 89% for malignant ones.

Conclusions: Surgical resection provided cure in all the patients with benign tumors. As insufficiency of exeresis is associated with all recurrences in malignant tumors, completeness of resection is in our experience the best prognostic factor in these forms.
The management of malignant pleural mesothelioma; single centre experience in 10 years. T. Aziz, A. Jilaihawi, D. Prakash. 2002;22(2):298-305. PubMed · Publisher

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=0.002). Survival was surprisingly, not affected by lymph node involvement (P=0.08) or pathological type of MPM (P=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.
Treatment of postoperative chylothorax through laparoscopic thoracic duct ligation. B.C. Vassallo, D. Cavadas, E. Beveraggi, et al. 2002;21(3):556-7. Case report PubMed · Publisher

Abstract

We report the laparoscopic transhiatal thoracic duct ligation to solve postoperative chylothorax after right total pleurectomy for malignant diffuse mesothelioma.
Trimodality management of malignant pleural mesothelioma. G. Maggi, C. Casadio, R. Cianci, et al. 2001;19(3):346-50. PubMed · Publisher

Abstract

Objective: We reviewed our experience with trimodality management of malignant pleural mesothelioma (MPM).

Methods: From September 1998 to August 2000, 32 consecutive patients with histological diagnosis of MPM underwent trimodality therapy, including surgery followed by adjuvant chemotherapy and radiation therapy. Surgery consisted of pleurectomy/decortication (P/D) or pleural-pericardial-pneumonectomy and diaphragm (PPPD). Pre-operative staging according to the Brigham Staging System was accomplished using computed tomography (CT) and magnetic resonance imaging (MRI); patients with evident extrapleural spread were excluded.

Results: Our series included 21 men and 11 women with a median age of 53.5 years (range 40-69). Histologically, there were 26 epithelial, four mixed and two sarcomatous MPM. Post-surgical staging was as follows: six patients were at Stage I; of these, two received a P/D and four a PPPD. Ten patients were at Stage II and all received a PPPD; 16 patients were at Stage III (under-staged pre-operatively): of these, nine patients presented extrapleural lymph node metastases (N2) and all received a PPPD, seven patients presented with chest wall or mediastinal invasion (T4) with macroscopic residual tumour, and all received a de-bulking P/D. We observed major complications in ten patients: six bleeding, two respiratory insufficiency and two nerve paralysis. There were two perioperative deaths (6.25% mortality). Twenty-seven patients out of 30 surviving surgery had a follow-up greater than 6 months; 21 patients out of 27 are alive with a median follow-up of 12.5 months.

Conclusions: (1) Trimodality therapy is feasible in selected patients with MPM and has an acceptable operative mortality rate. (2) Our current pre-operative staging based on CT/MRI looks rather inaccurate and needs to be improved. (3) The high rate of post-surgical N2 patients or with diffusion to the inferior surface of the diaphragm may suggest the use of routine mediastinoscopy and laparoscopy for a more appropriate patient selection.
18-FDG positron emission tomography in the evaluation of malignant pleural diseases - a pilot study. A. Carretta, C. Landoni, G. Melloni, et al. 2000;17(4):377-83. PubMed · Publisher

Abstract

Objective: The diagnostic approach to pleural diseases may be difficult. The CT scan, which is the current diagnostic technique, has limited accuracy both in the differentiation between benign and malignant pleural diseases and in the diagnosis of primary and metastatic pleural neoplasms. Invasive procedures, such as thoracoscopy, are therefore frequently required to complete the diagnostic approach. The increasing incidence of malignant pleural mesothelioma has led to the development of new treatment strategies, which still need to be fully validated. There is, therefore, a need for new diagnostic techniques that can lead to a definite diagnosis and a satisfactory evaluation of the response to treatment. Encouraging results have been reported with the F-18-labeled analogue of 2-deoxyglucose (18-FDG) positron emission tomography (PET) in the evaluation of chest tumors such as lung cancer. The aim of this study was to evaluate the role of 18-FDG PET in the diagnostic assessment of pleural diseases.

Methods: Patients with CT scan evidence of pleural thickening, or fluid, entered a study to evaluate the accuracy of 18-FDG PET in diagnosing pleural diseases. Image analysis was performed both with visual interpretation and using a semiquantitative method, standardized uptake values (SUV), on coronal, sagittal and axial reconstructions. The results of PET imaging were compared to histological data. PET was also performed before and after treatment in patients who underwent chemotherapy to evaluate the accuracy of this technique in the assessment of the response.

Results: Fourteen patients entered the study. Histology demonstrated a malignant pleural disease in 13 patients; malignant pleural mesothelioma in ten patients, adenocarcinoma in two and liposarcoma in one. Benign pleural disease was diagnosed in the remaining patient. PET assessment demonstrated significant 18-FDG uptake in 12 of the 13 patients with a malignant disease, also revealing distant metastases in two of them. A false-negative result was observed in a patient with an epithelial mesothelioma. The overall accuracy was 92%. A benign pleural disease without significant uptake was correctly diagnosed in another patient. An aspecific uptake was observed in two patients who had undergone pleurectomy and intrapleural chemotherapy. A decreased tracer uptake was observed after chemotherapy in four patients.

Conclusions: These preliminary results demonstrate that 18-FDG PET may have a great potential, both in the differential diagnosis of pleural diseases and in the evaluation of the response to treatment. At present, however, histological thoracoscopic diagnosis remains mandatory before planning treatment. Further studies in larger groups of patients are needed to draw definite conclusions on the role of PET in the assessment of pleural diseases.
A comparative evaluation of intrathoracic latissimus dorsi and serratus anterior muscle transposition. M.K. Widmer, T. Krueger, D. Lardinois, et al. 2000;18(4):435-9. PubMed · Publisher

Abstract

Background: Comparison of intrathoracic latissimus dorsi (LD) versus serratus anterior (SA) muscle transposition for treatment of infected spaces, broncho-pleural fistulae, and for prophylactic reinforcement of the mediastinum after extended resections following induction therapy.

Patients And Methods: Twenty LD and 17 SA transfers were performed for prophylactic reinforcement (11 LD; nine SA), and treatment of infections (nine LD; eight SA) from 1995 to 1998.

Results: The 30-day mortality was 0% following prophylactic reinforcement and 29% following treatment of infections (three LD; two SA). Prophylactic mediastinal reinforcement was successful in 11 of 11 patients with LD and nine of nine with SA transpositions, and treatment of infected spaces in eight of nine patients with LD and two of three with SA transfers. Morbidity requiring re-intervention consisted of flap necrosis (one LD), bleeding (one SA), and skin necrosis over a winged scapula (one SA). Subcutaneous seromas and chest wall complaints were more frequent following LD (45 and 36%, respectively) compared with SA transfers (29 and 27%, respectively), whereas impaired shoulder girdle function was more frequent after SA than after LD transfer (27 vs. 21%).

Conclusion: Intrathoracic LD and SA muscle transpositions are both efficient for the prevention or control of infections following complex thoracic surgery, and are both associated with similar and acceptable morbidity and long-term sequelae.
The long-term morbidity of pleuroperitoneal shunts in the management of recurrent malignant effusions. O. Genc, M. Petrou, G. Ladas, et al. 2000;18(2):143-6. PubMed · Publisher

Abstract

Objective: Over the last 15 years we have managed patients with malignant pleural effusion, using a single procedure with thoracoscopy and talc pleurodesis or shunt as appropriate. Talc pleurodesis remains our primary treatment option but in those patient shown to have the 'trapped lung syndrome', in whom pleurodesis would fail, we have been using a pleuroperitoneal shunt.

Methods: This retrospective review was undertaken to evaluate the mortality and morbidity of pleuroperitoneal shunts in the management of malignant pleural effusions and to assess their long-term results. Three hundred and sixty patients were treated for malignant effusions during the period 1983-1998, 160 (44.4%) of whom had a pleuroperitoneal shunt inserted. There were no intraoperative deaths and the hospital mortality was three patients (1.87%). Follow up was available for 88.1% of patients. The median survival of all malignant cases was 7.7 months (range 1-72 months). Mesothelioma patients survived somewhat longer with a median survival of 10.1 months.

Results: Shunt complication occurred in 21 patients (14.8%). Twelve patients developed shunt occlusion, requiring revision in five and replacement in seven. The shunt was removed in eight patients due to skin erosion in one patient and infection in seven patients. The distal limb of shunt was broken in one patient and the shunt was replaced. One patient developed malignant seeding along the chest wall at the site of shunt insertion but there were no incidences of peritoneal deposits. Effective palliation was achieved in 95% of patients.

Conclusions: Pleuroperitoneal shunt insertion provides effective and safe palliation for malignant pleural effusion when associated with the 'trapped lung syndrome'. There are however complications which require revision or shunt removal. There is no evidence that peritoneal deposits result from pleuroperitoneal shunting.

1990s

Mesothelioma--VATS biopsy and lung mobilization improves diagnosis and palliation. M.W. Grossebner, A.A. Arifi, M. Goddard, et al. 1999;16(6):619-23. PubMed · Publisher

Abstract

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.
A case of giant benign localized fibrous tumor of the pleura. M. Biçer, S. Yaldiz, S. Gürsoy, et al. 1998;14(2):211-3. Case report PubMed · Publisher

Abstract

A 60-year-old man had noted exertional dyspnea and left anterior chest pain. A chest roentgenogram showed the presence of a giant mass and computed tomography (CT) of the chest confirmed the mass with an inhomogeneous density in the left hemithorax. A transthoracic TruCut needle biopsy of the mass showed benign fibrous tissue. The patient underwent a thoracotomy. A tumor arose from the visceral pleura of left lower lobe and pedinculated. Size of the tumor was 19 x 18 x 7 cm and weighed 1500 g. It was successfully resected. The pathological diagnosis of the tumor was benign localized fibrous tumor of the pleura.
Extrapericardial solitary fibrous tumour of the pericardium. S.M. Andreani, L. Tavecchio, R. Giardini, et al. 1998;14(1):98-100. Case report PubMed · Publisher

Abstract

Solitary fibrous tumour (SFT) occurs most commonly in the pleura and is extremely rare in the pericardium. The authors report a case of a 60-year-old man in whom a large mediastinal mass was accidentally discovered. Computed tomography showed involvement of the left anterosuperior mediastinum with displacement of the trachea, large vessels and oesophagus; histopathological findings after complete resection of the neoplasia demonstrated an SFT of the pericardium, the first reported case with extrapericardial pattern of growth. A review of the literature on SFTs of the pericardium is provided.
Localized fibrous tumours of the pleura: 15 new cases and review of the literature. M. Suter, S. Gebhard, M. Boumghar, et al. 1998;14(5):453-9. Review PubMed · Publisher

Abstract

Objective: To present a series of localized fibrous tumours of the pleura (LFTP), to define the clinical and histopathological diagnostic criteria of this tumour, and to determine the optimal treatment and follow-up.

Methods: Review of the charts of the patients with the diagnosis of LFTP (formerly called benign fibrous mesothelioma), as well as of all the histological sections, including immunohistochemical stains. Review of the literature with special emphasis on the clinical and histological criteria of malignancy.

Results: During the last 30 years, we found 15 patients with a complete clinical chart and histological material, particularly paraffin blocks of the tumour. The mean age was 57 years (range 27-79). Eight patients were asymptomatic, and the remaining seven presented with non-specific symptoms. All but one had complete resection of the tumour, including partial lung resection in two and partial chest wall resection in three. The diagnosis was confirmed by histological review in 15 cases. Immunohistochemical stainings showed positivity for vimentin in all cases, for CD 34 in 80%, but were consistently negative for cytokeratins. Nine tumours were histologically classified as malignant. Among them, five recurred, two of which were responsible for death. One benign tumour recurred after 1 year, and was treated successfully by repeat resection and radiotherapy. Overall, 13 patients (86%) were alive with no evidence of disease between 10 months and 27 years after the first resection.

Conclusions: LFTP is a rare tumour which has a benign clinical course in over 80% of the cases, and is asymptomatic in half the patients. The diagnosis is difficult to establish before operation. Treatment consists of complete resection including adjacent structures if necessary. The clinical behaviour of LFTP cannot be predicted on the basis of histological aspects only. If histologically malignant tumours are more prone to recurrence and poor outcome, broad-based and locally invasive tumours bear a higher risk of recurrence. Long term follow-up is therefore mandatory in all cases in order to perform early re-resection when recurrence occurs.
Experimental assessment of photodynamic therapy with chlorins for malignant mesothelioma. H.B. Ris, A. Giger, V.I. Hof, et al. 1997;12(4):542-8. PubMed · Publisher

Abstract

Objective: Photodynamic therapy (PDT) with two chlorin sensitisers was assessed on nude mice bearing human mesothelioma xenografts, and on intrathoracic tissues of minipigs with the same drug-light conditions to optimise the antitumour activity of PDT while preventing photosensitising injury to normal tissues.

Methods: Laser light (20 J/cm2) at 652 nm was delivered to the xenografts 1-4 days after i.p. administration of 0.1 mg/kg m-tetrahydroxyphenyl-chlorin (mTHPC) or an equimolar dose of polyethylene glycol-derived mTHPC (pegylated mTHPC), respectively. The extent of tumour necrosis was assessed by histomorphometry. Intraoperative PDT was then performed to the thoracic cavity of minipigs through a sternotomy with the same drug-light conditions at drug-light intervals ranging from 12 h to 6 days after i.v. administration of mTHPC and pegylated mTHPC, respectively.

Results: Both, mTHPC and pegylated mTHPC, resulted in photosensitised necrosis of mesothelioma xenografts at drug-light intervals from 1 to 4 days but the extent of necrosis was significantly larger by use of pegylated mTHPC instead of mTHPC at a drug-light interval of 3 and 4 days. The optimal tumourcidal effect was achieved with pegylated mTHPC at a drug-light interval of 4 days. The photosensitising effect of mTHPC on intrathoracic tissues of minipigs revealed severe damage of virtually all tissues except nerves at short drug-light intervals. Tissue damage gradually became less at longer drug-light intervals and was absent at intervals of 3 days and longer. In contrast, pegylated mTHPC resulted in no obvious change to any structure at any drug-light interval assessed.

Conclusions: PDT with pegylated mTHPC reveals the potential of selective tumour destruction in this experimental setting and deserves further evaluation for intraoperative application in patients with malignant mesothelioma.
Pleurectomy/decortication for palliation in malignant pleural mesothelioma: results of surgery. O. Soysal, N. Karaoğlanoğlu, S. Demiracan, et al. 1997;11(2):210-3. PubMed · Publisher

Abstract

Objective: Surgery can only offer palliation in an attempt to slow the progression of malignant pleural mesothelioma (MPM). We want to assess the effectiveness and safety of pleurectomy/decortication in establishing a tissue diagnosis, and controlling pleural fluid accumulation and symptoms in patients with MPM.

Methods: We reviewed our pleurectomy results in 100 patients with MPM over a 19 year period. Major symptoms were chest pain, cough and dyspnea, and radiographic findings included pleural mass, pleural fluid and constriction of involved hemithorax.

Results: Approximately two thirds of the patients underwent surgery prior to tissue diagnosis. Eighty-nine patients had stage I and stage II disease, 8 and 81%, respectively. The patients underwent subtotal (44%) or total pleurectomy (56%). The surgical mortality rate was 1% (1/100) and the morbidity rate was 22%. Morbidity included prolonged air leak (n = 12), empyema (n = 6), reaccumulation of pleural fluid (n = 2) and wound infection (n = 2). Palliative results included dyspnea and cough relief in all patients, chest relief in 60 (85%) and pleural fluid control in 52 (96%) patients. Median survival was 17 months in MPM patients.

Conclusions: We conclude that pleurectomy/decortication safely provides both tissue diagnosis and effective of pleural effusion and symptoms and therefore excellent palliation in patients with MPM.
Surgical pathology of primary cardiac and pericardial tumors. C. Basso, M. Valente, A. Poletti, et al. 1997;12(5):730-7; discussion 737-8. PubMed · Publisher

Abstract

Objective: Retrospective study of surgical pathology experience on cardiac and pericardial tumors at the University of Padua in the era of immunohistochemistry and endomyocardial biopsy.

Methods: In the period 1970-1995, we studied 125 bioptic primary neoplasms: specimens were obtained from surgical resection in 116 cases, heart transplantation in 3, pericardiectomy in 3, endomyocardial biopsy in 2 and thoracoscopic biopsy in 1. Tumor histotype was established by light microscopy and more recently by immuno-histochemistry, using a large panel of antibodies, through avidin-biotin peroxidase method, against factor VIII-related antigen, ulex-europaeus, desmin, myoglobin, muscle-specific actin, smooth muscle-specific actin, vimentin, cytokeratins, leukocytic common antigen, neurofilaments and S100-protein.

Results: One hundred and thirteen were benign neoplasms: myxoma was the most frequent (87 cases) followed by pericardial cyst (8), endocardial papilloma (5), fibroma (3), rhabdomyoma (3), hematic cyst (2), teratoma (2), hemangioma (1), celothelioma (1) and lipoma (1). Malignancy was diagnosed in 12 cases, and consisted of pericardial mesothelioma (3), myxosarcoma (3), angiosarcoma (2), fibrosarcoma (2) and leiomyosarcoma (2); 4 of them were intracavitary atrial masses and were supposed to be atrial myxoma on the clinical ground. Differential diagnosis included endocardial thrombosis (10), metastasis of concealed extracardiac tumors (5), echinococcosis (3), and Loeffler's fibroplastic endocarditis (3). In 4 cases, cardiac mass histotype was defined without thoracotomy, through endomyocardial (3) and thoracoscopic (1) biopsy.

Conclusions: A large spectrum of cardiac tumors is observed in the surgical pathology practice. Although the diagnosis of cardiac masses is easily attainable by routine imaging techniques, differential diagnosis between primary and secondary tumors, malignant and benign forms, and non neoplastic masses, is achievable only by a thorough microscopic study of surgical resections. The role of the cardiac pathologist is becoming crucial as in other fields of oncology.
Transsternal transpericardial operations in the treatment of bronchopleural fistulas after pneumonectomy. G. Stamatis, G. Martini, L. Freitag, et al. 1996;10(2):83-6. PubMed · Publisher

Abstract

Between 1972 and 1993, 19 patients (15 males and 4 females) with bronchopleural fistulae and pleural empyema after pneumonectomy were treated with transsternal transpericardial operations and closure of the fistula. The underlying malignant disease was a non-small cell carcinoma in 12, a malignant epithelial mesothelioma in two, and an atypical carcinoid tumor in one case. One patient each presented with tuberculosis, chest trauma, and lung destroyed by bronchiectasis. Fistulas affected the right bronchial stump in 17, and the left in 2, cases after pneumonectomy. The time between pneumonectomy and transsternal transpericardial operation ranged between 1 month and 4 years. All patients were submitted to drainage and irrigation of the empyema cavity (2-4 weeks). In 16 patients a long bronchial stump was sutured or stapled, in three cases resection of a short stump with the distal trachea was followed by anastomosis of the trachea and left main stem bronchus. Irrigation of the pneumonectomy cavity was continued in all patients for 2 weeks. Transsternal transpericardial operation was successful in 15 patients. Two patients died in the first 30 days, of renal or respiratory failure without fistula recurrence. In two cases the fistula recurred; definitive healing was achieved using a great omentum flap and endoscopic application of fibrin glue and bone spongiosa. Transsternal transpericardial management of bronchus stump fistula after pneumonectomy is highly effective and offers advantages over the direct approach through the infected empyema cavity.
Diagnostic and therapeutic strategy in malignant pleural mesothelioma. D. Branscheid, S. Krysa, E. Bauer, et al. 1991;5(9):466-72; discussion 473. PubMed · Publisher

Abstract

We retrospectively analysed 301 patients with diffuse malignant pleural mesothelioma (235 male, 66 female; median age 59 years). Prognosis depended significantly on patient age, evidence of pain, loss of weight, tumour cell type, stage, local and distant metastasis, involvement of peritoneum and surgical treatment. The overall median survival rate was 238 days, after extended pleuropneumonectomy 284 days, and after decortication 315 days - significantly better than the prognosis in patients without surgical treatment or exploratory thoracotomy. Pleuropneumonectomy should only be considered in young patients with an epithelial cell-type tumour (possibly with adjuvant chemotherapy). Decortication seems nowadays to be the treatment of choice.

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