The management of the diaphragm during radical surgery for malignant pleural mesothelioma

Our plain-English summary of The management of the diaphragm during radical surgery for malignant pleural mesothelioma, by A.J. Sharkey, R. Bilancia, S. Tenconi, et al (European Journal of Cardio-thoracic Surgery, 2016).

The study

• Authors: A.J. Sharkey, R. Bilancia, S. Tenconi, A. Nakas, D.A. Waller
• Journal: European Journal of Cardio-thoracic Surgery
• Published: 2016;50(2):311-6
• Cited by: 12 articles, as counted by NIH iCite
• Read it: 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.

In plain English

This study reviewed the records of 314 patients who had radical surgery for malignant pleural mesothelioma between 1999 and 2014. Of these, 101 had extrapleural pneumonectomy and 213 had extended pleurectomy decortication. Pathology reports showed no tumour in the diaphragm muscle in 119 patients (37.9%), invasion short of the full thickness in 161 (51.3%), and full-thickness (transmural) invasion in 34 (10.8%). Diaphragm involvement was greater in women and in patients with lymph node spread. Among 235 patients with progression data, 57 later developed disease in the abdomen. This was not correlated with the level of diaphragm involvement. Survival was shorter with more diaphragm involvement (16.9, 11.2 and 9.3 months), but this was not significant after accounting for other survival factors. Overall survival from surgery did not differ significantly between patients whose disease later progressed in the abdomen (14.5 months) and those whose disease progressed elsewhere (13.0 months). The authors found no evidence that removing the diaphragm seeds tumour into the abdomen. Because invasion is hard to judge during surgery, they advocated removing the diaphragm in both operations. The article does not discuss asbestos exposure.

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.

What the study did and found

• Design: Retrospective review of patients from a single institution's prospectively updated database of radical mesothelioma surgery (case notes, electronic records and pathology reports)
• Who was studied: 314 patients with malignant pleural mesothelioma who had radical surgery (101 extrapleural pneumonectomy, 213 extended pleurectomy decortication) at University Hospitals Leicester, UK, 1999 to 2014; median age 62 years (range 14 to 81), 86.0% male, 75.5% epithelioid
• Exposure: Asbestos exposure is not reported. The factor studied was how far the tumour had invaded the diaphragm muscle on pathology (none, non-transmural, transmural), in relation to abdominal disease progression and survival after surgery.
• Main results:
  • Of 314 patients, 119 (37.9%) had no diaphragmatic involvement, 161 (51.3%) had non-transmural invasion and 34 (10.8%) had transmural invasion; 3 patients (0.96%) had disease that breached the peritoneum
  • There was a higher degree of diaphragmatic involvement in females (P = 0.01) and in patients with lymph node metastases (P = 0.01); neoadjuvant chemotherapy had no effect on the level of involvement (P = 0.92)
  • Progression data were available for 235 patients, of whom 57 developed abdominal progression (reported as 23.9%); there was no correlation between level of diaphragmatic involvement and abdominal disease as the first site of progression (rho = 0.01, P = 0.88)
  • In the transmural invasion group there was a trend (not statistically significant) toward more abdominal progression: 10 patients developed abdominal progression compared with 6 who had no progression at any site (P = 0.06)
  • Unadjusted median overall survival was 16.9 months with no diaphragmatic involvement, 11.2 months with non-transmural invasion and 9.3 months with transmural invasion (P = 0.01)
  • On multivariable analysis, degree of diaphragmatic involvement did not remain a significant predictor of overall survival
  • Overall survival, measured from surgery, was 14.5 months in patients who developed abdominal progression (n = 57) versus 13.0 months in those with progression elsewhere (n = 99), P = 0.79; and versus 16.7 months in patients with no detected progression (n = 79), P = 0.19
  • On multivariable analysis, transmural invasion remained a negative prognostic factor for disease-free interval (hazard ratio 1.962, 95% confidence interval 1.186 to 3.247, P = 0.01)
  • Of 314 patients, 20 (6.4%) had early dehiscence of the prosthetic diaphragm patch and 7 (2.2%) had late dehiscence; survival did not differ significantly by dehiscence status (P = 0.245)
• The authors' conclusion: The authors concluded they found no evidence that tumour is seeded into the abdomen during removal of the diaphragm. Given the difficulty of judging diaphragm involvement during surgery and the poorer survival linked to leaving visible tumour (R2 resection), they advocated resecting the diaphragm in both EPP and EPD.
• Limitations the authors state:
  • Numbers were small in the subgroups comparing survival after abdominal progression by level of diaphragmatic invasion
  • Only 3 patients received Permacol patches, too few for meaningful comparison with other patch types

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Diaphragm, Pleural Mesothelioma, Parietal Pleura, Pleurectomy/Decortication (P/D), Extrapleural Pneumonectomy (EPP), Pathology, Epithelioid, Neoadjuvant Chemotherapy.

Related studies

• The new case for cervical mediastinoscopy in selection for radical surgery for malignant pleural mesothelioma — A. Nakas, D. Waller, et al. (2012)
• Long-term Survival and Propensity Score Matched Outcomes of Bilateral vs. Unilateral Diaphragm Interventions in Cytoreductive Surgery plus Intra-peritoneal Chemotherapy — B. Singh, G. Singh, et al. (2018)
• Surgery as part of radical treatment for malignant pleural mesothelioma — D.A. Waller, S. Tenconi (2017)
• How does the timing of chemotherapy affect outcome following radical surgery for malignant pleural mesothelioma? — A.J. Sharkey, K.J. O'Byrne, et al. (2016)
• Efficacy of intra-operative unilateral diaphragm plication for patients undergoing unilateral phrenicotomy during extended surgery — T. Tokunaga, N. Sawabata, et al. (2010)
• Predictors of long-term survival following radical surgery for malignant pleural mesothelioma — A. Nakas, D. Waller (2014)

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