An overview of neoadjuvant chemotherapy in the multimodality treatment of malignant pleural mesothelioma

Malignant Pleural Mesothelioma (MPM) is an aggressive tumour with poor prognosis and increasing incidence in industrialized countries because of the previous widespread exposure to asbestos fibres and to the long lag period from time of exposure and the diagnosis of the disease.     

What can independent research for mesothelioma achieve to treat this orphan disease?

Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with a poor prognosis, as current therapies are ineffective. Despite the increased understanding of the molecular biology of mesothelioma, there is still a lack of drugs that dramatically enhance patient survival.

Area Covered: This review discusses recent and complete clinical trials supported by the NIH, other U.S. Federal agencies, universities and organizations found on clinicaltrials.gov. Firstly, chemotherapy-based trials are described, followed by immunotherapy and multitargeted therapy. Then we introduce drug repositioning and the use of drug docking as tools to find new interesting molecules. Finally, we highlight potential molecular pathways that may play a role in mesothelioma biology and therapy.

Expert Opinion: Numerous biases are present in the clinical trials due to a restricted number of cases, inappropriate endpoints and inaccurate stratification of patients which delay the finding of a treatment for MPM. The most crucial issue of independent research for MPM is the lack of more substantive funding to translate these findings to the clinical setting. However, this approach is not necessarily scientific given the low mutational load of mesothelioma relative to other cancers, and therefore patients need a more solid rationale to have a good chance of successful treatment     

A hydrodynamic study of pleural drainage systems: some practical consequences

BACKGROUND: A pleural drainage system must be capable of efficiently evacuating the air or fluids from the pleural cavity so that adequate lung reexpansion can take place. The air flow and negative pressure of the system will depend on the particular design of each model. This experimental study analyzes the specifications and performance of the pleural drainage systems currently on the market. METHODS: Thirteen models of pleural drainage systems connected to wall suction were examined. The models were classified into the following three groups: dry systems; wet systems; and single-chamber systems. We determined the ambient air flow and the negative pressure generated according to the suction level. The components of each model are also described. RESULTS: Under normal conditions, dry (except for the Sentinel Seal; Sherwood Medical; Tullamore, Ireland), wet, and single-chamber systems reach similar air flow rates (17 to 30, 24 to 27, and 22 to 28 L/min, respectively). With higher wall suction levels, wet systems increase the air flow (26 to 49 L/min) but the negative pressure becomes unstable because of the water loss phenomenon, dry systems increase the air flow (29 to 50 L/min) without modifying the regulator pressure, and single-chamber systems also raise the air flow (45 to 51 L/min) but increase the negative pressure. When there is an air leak, dry systems (except for the Sentinel Seal) lose less negative pressure than the other systems. CONCLUSIONS: The functioning of these systems can be optimized only by applying a suitable wall suction level adjusted to each case. Although the three types of systems are capable of evacuating adequate air flow rates, the negative pressure and the capacity to maintain it in the presence of an air leak are different in each system. Being fitted with valves and not water compartments makes the dry systems the safest and the ideal for use when the patient has to be moved.     

Success rate of medical thoracoscopy and talc pleurodesis in malignant pleurisy: A single‐centre experience

Background and objective

Malignant pleurisy is associated with advanced oncological disease and dyspnoea is the most common presenting symptom. Pleurodesis is the preferred palliative and supportive treatment option, targeting symptom relief. The identification of clinical and endoscopic features that determine the success of talc pleurodesis in malignant pleurisy could guide clinical decision‐making.

Methods

All symptomatic patients with malignant pleurisy subjected to talc pleurodesis through medical thoracoscopy between January 2012 and December 2015 were included. Univariate and multivariate analyses were performed to identify factors associated with successful pleurodesis.

Results

Of the 155 patients, 122 (78%) were classified as having a successful pleurodesis based on clinical and radiological criteria. Factors associated with unsuccessful pleurodesis (univariate analysis) were the presence of pleural adhesions (odds ratio (OR): 0.43 (95% CI: 0.19–0.96); P = 0.04), extensive spread of pleural lesions (OR: 0.17 (95% CI: 0.05–0.59); P = 0.001), the use of systemic corticosteroids (OR: 0.28 (95% CI: 0.10–0.83); P = 0.02) and a prolonged time period between the clinical diagnosis of the pleural effusion and the moment of pleurodesis (OR: 0.14 (95% CI: 0.06–0.32); P < 0.0001). The latter being associated with failure of pleurodesis in a multivariate analysis (OR: 0.08 (95% CI: 0.01–0.25); P < 0.0001). Chest ultrasound prior to pleurodesis showed a sensitivity of 91% and a specificity of 88% in predicting the success of pleurodesis.

Conclusion

The success rate of pleurodesis in malignant pleurisy could potentially be enhanced by correct patient selection and early referral for pleurodesis. Ultrasonic assessment of pleural adhesions and potential lung expansion prior to pleurodesis is useful in clinical decision‐making.

     

Role of medical thoracoscopy in the treatment of tuberculous pleural effusion

Background

Fibrous tuberculous pleural effusion (TPE) represents common disease in tuberculous clinic. Medical thoracoscopy has been used to treat pleural empyema and shown promising outcomes, but data of its use in multiloculated and organized TPE remains limited to know.

Methods

The study was performed on 430 cases with TPE. The cases were divided into free-flowing, multiloculated effusion and organized effusion group. Each group was subdivided into two or three types of therapeutic approaches: ultrasound guided pigtail catheter, large-bore tube chest drainage and medical thoracoscopy. Patients with multiloculated or organized effusions received streptokinase, introduced into the pleural cavity via chest tubes. The successful effectiveness of the study was defined as duration of chest drainage, time from treatment to discharge days and no further managements.

Results

Patients with organized effusion were older than those with free-flowing effusion and incidence of organized effusion combined with pulmonary tuberculosis (PTB) was higher than those of multiloculated effusion and free-flowing effusion respectively. Positive tuberculosis of pleural fluid culture was higher in organized effusion than that in free-flowing effusion. Sputum positive for acid-fast bacillus (AFB) in organized effusion was higher than that in multiloculated effusion and free-flowing effusion. Medical thoracoscopy showed significant efficacy in the group of multiloculated effusion and organized effusion but free-flowing effusion. No chronic morbidity and mortality related to complications was observed.

Conclusions

Medical thoracoscopy was a safe and successful method in treating multiloculated and organized TPE.     

Rapidly recurring massive pleural effusion as the initial presentation of sarcoidosis: A case report

Rationale:Sarcoidosis is a multisystem granulomatous disease with unknown etiology. It affects mainly the lungs, but it can affect almost any other organ. Nevertheless, pleural involvement with the development of pleural effusion is relatively rare. It is usually mild and responsive to treatment with systemic steroids. Here we present a case of rapidly recurring massive unilateral pleural effusion caused by sarcoidosis that was resistant to systemic steroids.Patient concerns:A 55-year-old lady presented with shortness of breath of 2-months duration. No other respiratory symptoms were reported. On physical examination, there were signs of left-sided pleural effusion, splenomegaly, and inguinal lymph nodes. These findings were confirmed by chest x-ray showing massive pleural effusion. Work up of the effusion revealed an exudative effusion with lymphocyte predominance. Pan-computed tomography scan revealed multiple thoracic, abdominal and inguinal lymphadenopathy; additionally, a left-sided pleural effusion and an enlarged spleen; that contained variable hypodense nodular lesions. Positron emission tomography-computed tomography showed intense uptake in the spleen and the lymph nodes. Inguinal lymph node biopsy showed non-necrotizing granulomatous inflammation. Due to suspicion of malignancy, left medical thoracoscopy was done, and biopsy of the parietal pleura showed nonspecific inflammation without evidence of malignancy or tuberculosis.Diagnosis:Sarcoidosis was diagnosed based on the finding of the non-necrotizing granulomatous inflammation with no evidence of malignancy or infection on several microbiological and pathological samples.Interventions:The patient was treated with repeated pleural fluid drainage. Steroids failed to prevent pleural effusion recurrence. Surgical left side pleurodesis was eventually performed.Outcomes:At more than 1 year follow up, the patient showed no recurrence of pleural effusion or development of any other symptoms.Lessons:Sarcoidosis may rarely present with massive pleural effusion, as this presentation is rare; it is imperative to rule out other causes of massive pleural effusion. Massive pleural effusion in sarcoidosis may be steroid-resistant. Pleurodesis may have a role in such a scenario.     

Recurrent monocular exudative retinal detachment as the first manifestation of squamous cell lung cancer: A case report

Rationale:In this report, we present an extremely rare case of recurrent monocular exudative retinal detachment without concomitant ocular metastases. This turned out to be the first symptom of squamous cell lung cancer.Patient concerns:A 63-year-old woman was referred to our ophthalmology clinic by her primary care physician with a complaint of deteriorating vision in her right eye that had started four months prior, without concomitant pain.Diagnoses:We observed a detachment in the lower part of the retina during her ophthalmoscopy. We did not find any tears, holes, or degenerative changes in the periphery of the retina of the right eye during the surgery. In addition, plaques, tumor masses, and metastases were absent. Therefore, we diagnosed her with unilateral paraneoplastic exudative retinal detachment. Imaging tests performed before surgery revealed perihilar density with a visible air bronchogram in the middle field of the left lung. This turned out to be squamous cell carcinoma.Interventions:Patient underwent pars plana vitrectomy and routine laboratory and imaging tests before the procedure that utilized 20-gauge instrumentation. The subretinal fluid and was drained and a tamponade using Densiron (Fluoron Co, Neu-Ulm, Germany) was applied. After ophthalmic treatment, patient underwent complex oncological treatment based on chemotherapy and radiotherapy.Outcomes:Despite the application of heavy silicone oil (Densiron) into the vitreous chamber, we observed a recurrence of retinal detachment in the right eye during the follow-up visit, 13 months after the first ophthalmic surgery. Following subsequent pars plana vitrectomy, the Densiron and subretinal membranes were removed. Despite oncological treatment, the patient died, twenty months after the appearance of the first ocular symptoms.Lessons:Exudative retinal detachment without tumor metastasis to the eyeball can be one of the first signs of lung cancer in rare cases. Multidisciplinary care and imaging methods with greater accuracy will provide comprehensive care to the patients. It will not only facilitate timely detection and treatment of lung tumors but also for a plethora of oncological diseases.