Pleural mesothelioma: is the surgeon still there?

Malignant pleural mesothelioma (MPM) is a rare malignancy with some unique characteristics. Tumor biology is aggressive and prognosis is poor. Despite more knowledge on histology, tumor biology and staging, there is still a relevant discrepancy between clinical and pathologic staging resulting in difficult prediction of prognosis and treatment outcome, making treatment allocation more challenging than in most other malignancies. After years of nihilism in the late 80s, a period of activism started evaluating different treatment protocols combined with research driven mainly by academic centers; at the time, selection was based on histology and stage only. This period was important to gain knowledge about the disease. However, the interpretation of data was difficult since selection criteria and definitions varied substantially. Not surprisingly, until now there is no common agreement on best treatment even among specialists. Hence, a review of our current concepts is indicated and personalized treatment should become applicable in the future. Surgery was and still is an issue of debate. In principle, surgery is an effective approach as it allows macroscopic complete elimination of a tumor, which is relatively resistant to medical treatment. It helps to set the clock back and other therapies that have also just a limited effect can be applied sequentially before or after surgery. Furthermore, to date best long-term outcome is reported from surgical series in combination with other modalities. However, part of the community considers surgery associated with too high morbidity and mortality when balanced to the limited life expectancy. This criticism is understandable, since poor results after surgery are reported. The present article will review the indication for surgery and discuss the different procedures available for macroscopic complete resection-such as lung-preserving (extended) pleurectomy/decortication as well as extrapleural pneumonectomy to illustrate that 'The surgeon is still there!

Prospective validation and extension of the Multimodality Prognostic Score for the treatment allocation of pleural mesothelioma patients

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. Keywords: Extended pleurectomy decortication; Extrapleural pneumonectomy; Malignant pleural mesothelioma; Multimodality Prognostic Score; Multimodality therapy; albumi

Recipient Comorbidities for Prediction of Primary Graft Dysfunction, Chronic Allograft Dysfunction and Survival After Lung Transplantation

Since candidates with comorbidities are increasingly referred for lung transplantation, knowledge about comorbidities and their cumulative effect on outcomes is scarce. We retrospectively collected pretransplant comorbidities of all 513 adult recipients transplanted at our center between 1992–2019. Multiple logistic- and Cox regression models, adjusted for donor-, pre- and peri-operative variables, were used to detect independent risk factors for primary graft dysfunction grade-3 at 72 h (PGD3-T72), onset of chronic allograft dysfunction grade-3 (CLAD-3) and survival. An increasing comorbidity burden measured by Charleston-Deyo-Index was a multivariable risk for survival and PGD3-T72, but not for CLAD-3. Among comorbidities, congestive right heart failure or a mean pulmonary artery pressure >25 mmHg were independent risk factors for PGD3-T72 and survival, and a borderline risk for CLAD-3. Left heart failure, chronic atrial fibrillation, arterial hypertension, moderate liver disease, peptic ulcer disease, gastroesophageal reflux, diabetes with end organ damage, moderate to severe renal disease, osteoporosis, and diverticulosis were also independent risk factors for survival. For PGD3-T72, a BMI>30 kg/m2 was an additional independent risk. Epilepsy and a smoking history of the recipient of >20packyears are additional independent risk factors for CLAD-3. The comorbidity profile should therefore be closely considered for further clinical decision making in candidate selection

Case report: Surgical repair of a large tracheo-esophageal fistula in a patient with post-transplant esophageal lymphoproliferative disorder

Introduction and importance The management of large malignant tracheo-esophageal fistulas (TEF) is not standardized. Herein, we report a case with a malignant TEF associated with esophageal post-transplant lymphoproliferative disorder (PTLD) for whom we successfully performed a surgical repair. This contributes to the knowledge on how to treat large acquired malignant TEFs. Case presentation A 69-year old male presented with a one-week history of fever, productive cough and bilateral coarse crackles. In addition, he described a weight loss of 10 kg during the past three months. The patient's history included a kidney transplantation twenty years ago. Esophagogastroduodenoscopy with a biopsy of the esophagus was performed nine days before. Histopathology showed a PTLD of diffuse large B-cell lymphoma subtype. Subsequent diagnostics revealed a progressive TEF (approx. 2.0 × 1.5 cm) 3.0 cm above the carina. PET-CT scan showed an esophagus with slight tracer uptake in the middle third (approx. 11.5 cm length, SUV max 7.4). After decision against stenting, transthoracic subtotal esophagectomy with closure of the tracheal mouth of the fistula by a pedicled flap was performed. PTLD was treated with prednisone and rituximab. Tumor progression (brain metastasis) led to death 95 days after surgery. Clinical discussion The treatment of a malignant TEF is complex and personalized while both the consequences of the esophago-tracheal connection and those of the underlying responsible diagnosis have to be considered concurrently. In this case, we considered surgery as the best treatment option due to a relatively good prognosis of the underlying diagnosis (PTLD) and a large fistula. Esophageal or dual stenting, the treatment of choice for small malignant TEF, would have been associated with a high risk of failure due to the wide trachea, extensively dilated esophagus, proximal location and large diameter of the fistula. Conclusion Surgery can be considered for patients with a large acquired malignant TEF and positive long-term prognosis of the underlying diagnosis. Due to the complexity of TEF management, immediate pre-operative multidisciplinary discussion is advised

Perioperative Anaesthesiological Management of Malignant Pleural Mesothelioma Patients Undergoing Extrapleural Pneumonectomy (EPP) and Extended Pleurectomy/Decortication ((E)PD)

Introduction: Macroscopic complete resection (MCR) within a multimodality treatment concept offers currently the best survival for malignant pleural mesothelioma patients. The current standardised therapy is within a multimodality approach including (neo-)adjuvant chemotherapy followed by macroscopic complete resection (MCR). However, MCR in form of extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication ((E)PD) is correlated with significant morbidity and mortality if not performed in high volume centres as described previously according to the literature. In addition, there exist no standardised anaesthesiological protocol for this surgical approach according to the literature. Methods: At our institution, diagnosed mesothelioma patients up to an International Mesothelioma Interest Group (IMIG) stage III receive induction chemotherapy followed by either EPP or (E)PD and in certain cases additional adjuvant therapy. In the period 1999-end 2019, 362 patients were intended to be treated and 303 underwent induction chemotherapy followed by MCR. MCR can be achieved either by EPP or (E)PD. Both procedures request a good teamwork between the surgeon and the anaesthesiologist. Conclusion: Although, there has been a shift lately from EPP towards lung sparing procedure (E)PD, both surgical approaches are still performed to date and is a challenging procedure for both, the surgeon as well as the anaesthesiologist. Herewith, we present our institutional perioperative standard operating procedures for the surgical and anaesthesiological management of EPP or (E)PD according to international terms of reference

Sleeve resections with unprotected bronchial anastomoses are safe even after neoadjuvant therapy†

OBJECTIVES Sleeve resection is the operation of choice in patients with centrally located tumours, in order to avoid a pneumonectomy. Most surgeons protect the bronchial anastomoses with tissue to prevent insufficiencies. The purpose of this study is to report on outcome of unwrapped bronchial anastomoses, especially after neoadjuvant chemo- or chemoradiotherapy. METHODS Between 2000 and 2010, 103 patients [59 years (range 16-80), 40 females] underwent bronchial sleeve resections without coverage of the anastomosis with a tissue flap. We retrospectively reviewed the data for morbidity, mortality and survival, especially with regard to the type of resection, neoadjuvant therapy and stage. RESULTS Sleeve lobectomy was performed in 88, sleeve bilobectomy in 8, sleeve pneumonectomy in 4 and sleeve resection of the main bronchus in 3 patients. Twenty-seven patients had a combined vascular sleeve resection. Neoadjuvant chemotherapy was performed in 20 and radiochemotherapy in 5 patients. Non-small cell lung cancer (NSCLC) was present in 76 patients (squamous cell carcinoma in 44, adenocarcinoma in 24, large cell carcinoma in 6and mixed cell in 2) and neuroendocrine tumour in 20 and other histological types in 7 patients. The pathologic tumour stage in NSCLC was stage I in 26, stage II in 26, stage IIIA in 16, stage IIIB in 7 and stage IV in 1 patient. There were no anastomotic complications, especially no fistulas. One patient developed narrowing of the intermediate bronchus without need for intervention. Twenty-four patients had early postoperative complications, including 11 surgery-related complications (air leakage, nerve injury, haemothorax or mediastinal emphysema). The 30-day mortality was 3% (one patient died due to heart failure and two with multiorgan failure). The 5-year survival rate was 63% in NSCLC patients and 86% in neuroendocrine tumour patients. CONCLUSIONS Sleeve resection without wrapping the bronchial anastomoses with a tissue flap is safe even in patients who underwent neoadjuvant chemo- or chemoradiotherapy. Therefore, wrapping of the bronchial anastomoses is not routinely mandator

Biomolecular and clinical practice in malignant pleural mesothelioma and lung cancer: what thoracic surgeons should know†

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 articl

Cost-effectiveness analysis of surgical lung volume reduction compared with endobronchial valve treatment in patients with severe emphysema

BACKGROUND Lung volume reduction, either by surgery or bronchoscopically by endobronchial valve treatment have been shown to be a cost-effective alternative compared with conservative therapy. However, there is no comparative analysis of lung volume reduction by surgery and bronchoscopic lung volume reduction using endobronchial valves. OBJECTIVES The aim of this retrospective study was to provide a cost-effectiveness analysis of lung volume reduction by surgery compared with bronchoscopic lung volume reduction using endobronchial valves. METHODS The effectiveness of lung volume reduction was assessed using forced expiratory volume in the first second (FEV1), residual volume (RV) and 6-minute walking distance (6MWD), measured at baseline and at 4 to 12 weeks. Cost unit accounting derived from SwissDRG was used as a surrogate of the costs from the payer's perspective. RESULTS In total, 67 patients (37 men and 30 women) with a mean age of 68.3 ± 7.4 years were included. Both clinical effectiveness and costs were comparable between surgical and bronchoscopic lung reduction. The incremental cost-effectiveness ratios (ICERs) for bronchoscopic compared with lung volume reduction by surgery for FEV1, RV and 6MWD were -101, 4 and 58, respectively. For RV and 6MWD, it could be shown that endobronchial valve treatment is justified as a probably cost-effective alternative to lung volume reduction by surgery. Endobronchial valve treatment resulted in an improvement of 0.25 quality-adjusted life years (QALYs) and an ICER of € 7657 per QALY gained. CONCLUSION A robust statement on the superiority of one of the two procedures in terms of cost-effectiveness cannot be made from the present study. Therefore, the study is not suitable for resource allocation. Two upcoming trials comparing lung volume reduction surgery and endobronchial valve treatment may be able to answer this question