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What is the optimal management of malignant pleural effusions?

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Guideline contents > What is the optimal management of malignant pleural effusions?
Clinical practice guidelines for the treatment of lung cancer

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Australian Government / Cancer Australia

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Peters, M, Barnett, S, Gary Hammerschlag BSc, MBBS, FRACP, Cancer Council Australia Lung Cancer Guidelines Working Party. Clinical question:What is the optimal management of malignant pleural effusions? . In: Clinical practice guidelines for the treatment of lung cancer. Sydney: Australian Government / Cancer Australia. [Version URL: https://wiki.cancer.org.au/australiawiki/index.php?oldid=185023, cited 2023 Sep 23]. Available from: https://wiki.cancer.org.au/australia/Guidelines:Lung_cancer.


Last modified:
4 May 2018 06:31:25



What is the optimal management of malignant pleural effusions?

Introduction

Malignant pleural effusion (MPE) is a common problem for patients with metastatic cancer. Symptoms may include dyspnoea and cough. Effective palliation of symptoms with the least morbidity is the goal of management..[1] The mechanisms that underpin the breathlessness are not well defined but are likely to extend beyond the effect of lung compression/deflation. Imbalance between respiratory effort and diaphragm motion may contribute to the complex sensation that is breathlessness.[2][3] Therefore, symptomatic benefit from draining effusions with apparently minimal lung expansion can be seen.

Management options include recurrent needle drainage, drainage by long term catheter, pleurodesis via instilling of sclerosant either by bedside (blind or ultrasound guided) insertion of chest tube or at VATS, and pleurectomy by VATS or an open approach. In cases of incomplete re expansion, options include long term catheter drainage and pleurectomy / decortication by VATS or an open approach.

Prevention of fluid re-accumulation

Repeated simple aspiration should be reserved for patients with very poor prospects for survival but in whom aspiration produces a clinical benefit. The evidence that fluid recurs and that interventions are effective is based on clinical experience and before-after comparisons of fluid accumulation in patients in many intervention studies. However, randomised comparisons of simple aspiration with other interventions are lacking. In patients with better performance status, repeated simple aspiration may lead to adhesion formation that can in the future make lung expansion and pleural adhesions more difficult or less effective. Insertion of an indwelling intercostal catheter alone, without any attempt at pleurodesis, is not recommended.[4] Survival is significantly improved in patients undergoing pleurodesis compared with thoracentesis regardless of performance status.[5] The success rate of pleurodesis varies with the clinical characteristics of patients and the techniques used. Where the lung does not expand and therefore apposition of the visceral and parietal pleura does not develop, pleurodesis cannot be achieved. At a 3 month analysis, repeat aspirations are cheaper than tunnelled pleural catheters, followed by bedside pleurodesis and thoracoscopic pleurodesis. At 12 months, bedside pleurodesis is cheaper than tunnelled pleural catheter followed by thoracoscopic pleurodesis and repeated aspirations.[6]

Verma et al, investigated whether the addition of a Tyrosine Kinase Inhibitor (TKI) against Epidermal Growth Factor Receptor (EGFR) in patients with a malignant pleural effusion is more successful in preventing pleural fluid re-accumulation following initial drainage. There was no significant difference in effusion-progression-free survival (p=0.31), and no difference in time to pleural fluid recurrence (p=0.59). Median survival in TKI versus TKI plus talc pleurodesis vs TKI without talc pleurodesis was 14.1 vs 19.2 vs 11.7 months.[7]

Long-term tunnelled catheter

Tunnelled pleural catheters (TPCs) are designed to allow ambulatory or home care. The catheter consists of an intrathoracic end, a segment that is tunneled under the skin to the insertion site and a port to which a suction bottle is attached to facilitate intermittent drainage.[8] It is generally applied in cases where lung re-expansion has not been achieved, or is not expected, but a benefit of drainage has still been apparent. They can be used after failed pleurodesis.[9] Even in cases where re-expansion is not anticipated, there is a small but significant rate of spontaneous pleurodesis.[10][11][12] They can be used as a means to instil talc and achieve pleurodesis.[13] Advantages of this option include: insertion under local anaesthetic, early ambulation and short hospital stay. Disadvantages include: ongoing cost of drainage bottles (presently met most often by the patient) and the requirement of longterm foreign body protruding from the chest with respect to infectious risk and patient preference. Overall, cost effectiveness is greater in patients with shorter life expectancy,[14] but the cost transfer from hospital to individual patients is problematic.

Compared to bedside talc pleurodesis, tunnelled pleural catheters have a higher success of reliable drainage/pleurodesis of unilateral malignant pleural effusions (62% vs 46%, p=0.064), lower 30 day mortality (8.7 vs 5.9, p-0.036) and longer survival with effusion control (83% vs 52%, p=0.024).[15] Median hospital stay is less with a tunnelled pleural catheter, with a significant improvement in quality of life (p=0.02).[16] Dyspnoea scores and quality of life scores are improved post insertion of tunnelled pleural catheters.[17]

Pleuroscopic pleurodesis with insertion of a tunnelled pleural catheter minimises hospital length of stay. There is an improvement in dyspnoea scores and performance indexes post procedure.[18][19] Freeman et al also found a shorter length of stay with tunnelled pleural catheter compared to traditional talc poudrage (6 days vs 3 days, p<0.0017). There was a shorter time from surgery to systemic therapy with a tunnelled pleural catheter compared to talc poudrage (17 days vs 9 days, p<0.0001).[20]

In patients with a haematologic malignancy and a malignant effusion, an insertion of an indwelling pleural catheter achieves spontaneous pleurodesis in 23% of cases. The most common haematologic malignancies were lymphoma (62%) followed by Leukaemia (21%) and Multiple Myeloma (13%). The overall infection rate was 7.7% and the most common cause of removal was patient death. The mean in-situ dwell time was 89.9 +/- 127.1 days. [21]

A systematic review of tunnelled pleural catheter with chemical pleurodesis (talc and doxycycline), showed no significant difference in success (p=0.27), although compared with talc specifically, there was a relative risk of 0.66 (95 CI 0.52-0.84). Against all sclerosants there was no difference in complications (p=0.09), although against talc specifically, the relative risk was 3.01 (95% CI 1.57 vs 5.76).Length of stay was significantly shorter for tunnelled pleural catheter complared with control. [22]

Use of intrapleural streptokinase for multiloculated malignant pleural effusions

Saydam et al, in a randomised controlled trial, found a significant improvement in mean drainage in patients receiving streptokinase compared to control. There was no significant difference in recurrence rate of pleural fluid.[23]

Intercostal catheter drainage plus sclerosant instillation

To achieve pleurodesis using the catheter/sclerosant approach, a catheter is inserted under LA into the pleural space and fluid is drained. After drainage, a mixture of sclerosant and local anesthetic is injected into the pleural space. Pleural fluid drainage beyond 24-48 hours may not increase the chance of successful pleurodesis[24] and the practice of leaving the catheter in situ until daily drainage has fallen below a certain volume is not evidence based. Success rate, measured by failure of fluid re-accumulation requiring any further procedure is over 70%[1][25][26][27] Procedural risks should be low if the procedure is performed following current guidelines that include the use of bedside ultrasound.[28]

The drainage of pleural fluid does not need to be below 300ml per day prior to attempting pleurodesis. The success rate of pleurodesis is not significantly different if pleurodesis is attempted when all fluid has been drained (as per chest radiography) or when daily drainage is less than 300ml per day. This significantly reduces hospital length of stay.[29]

Patients receiving treatment for their malignancy have a significantly longer survival time than those not receiving treatment in conjunction with pleurodesis.[30]

Recommended catheter size to achieve pleurodesis using an intercostal catheter

Historically, large bore ( >20F) catheters were used for pleurodesis. One justification for their continued use after smaller, tube over guide-wire, catheter systems became available was that smaller tubes might become blocked by the talc slurry or viscous pleural drainage. Talc slurry will pass through 12F catheters and the blockage rate of size 8F-12F tubes even when used for drainage of empyema was 8% and even lower in non-infected effusions.[31] Intercostal catheters larger than 20F, as traditionally used, may not increase the success rate but may increase complications and pain. Catheters in the range 12-14F may be as effective as larger tubes.[32][33][34][30] Rahman et al, compared 12F and 24F chest tubes to determine clinical efficacy and pain scores. Smaller chest tubes were associated with higher pleurodesis failures compared with larger chest tubes. There was higher complication rates in the 12F group compared to the 24F group, although pain scores were less in the group with smaller tubes compared to larger tubes (p=0.04). Non-Steroid Anti-Inflammatory Drugs (NSAID) were non-inferior to opiated for pleurodesis failure, with more rescue analgesia required in the NSAID group. [35]

Pigtail Catheter versus intercostal tube for pleurodesis of malignant pleural effusions

Ghoneim at al compared pigtail catheters versus intercostal tubes for pleurodesis of malignant pleural effusions. 66% of patients in the pigtail catheter arm compared to 54% of patients in the intercostal catheter arm achieved pleurodesis, p=0.22). There was a significantly higher complication rate in the intercostal tube arm compared to the pigtail catheter arms (86% vs 44%, p<0.0004).[36] Srour et al found a significant improvement in pleural effusion control (OR 2.1 95% CI 1.2-3.7), as well as significant improvement in survival time and effusion free time.[37]

VATS talc pleurodesis versus bedside intercostal catheter pleurodesis

Terra et al[38] randomised 60 patients with recurrent MPE (17 with NSCLC), >90% expansion after thoracentesis and KPS > 70% to VATS talc poudrage under general anesthesia versus bedside chest tube and talc slurry. Patients who underwent VATS talc poudrage more often had complete postoperative lung expansion than those who received talc slurry administered through a chest tube (60% versus 30%, [p = 0.027]). Whilst the authors emphasise that no difference was found in quality of life or requirement of re intervention between the groups, no power calculation was reported with regard to these outcomes and as such a negative result is difficult to interpret. There was a trend toward incomplete initial re expansion being associated with both clinical recurrence (2/27 versus 7/33 [p=0.15]) and complication (5/27 versus 11/33 [p=0.20]).

Yim et al[39] randomised 57 patients (33 with NSCLC) to VATS talc insufflation under general anesthesia versus talc slurry at the bedside. There was no statistically significant difference between the two groups of patients with respect to chest drainage duration, post procedural hospital stay, parenteral narcotic requirement, complications, or recurrence (1/28 versus 3/29 [NS]). No power calculation was reported.

Dressler et al[26] randomised 482 patients (182 with NSCLC) to VATS with talc insufflation under general anesthesia (TTI) versus bedside chest tube and talc slurry. Thirty day freedom from radiographic recurrence among surviving patients whose lungs initially re-expanded > 90% favoured VATS, but did not reach significance (78% versus 71% [NS]). Patients with primary lung or breast cancer had statistically significantly higher success with TTI than with TS (82% versus 67% [p = 0.022]). Respiratory complications were more common after TTI (13.5% versus 5.6% [p = 0.007]). There was no difference in mortality. Patient perceptions of pain control (p = 0.07), comfort (p = 0.019) and medical safety (p = 0.013) favoured TTI. Fatigue was significantly better after TTI (p = 0.016).

Three meta analyses have addressed rate of recurrence of MPE after VATS talc pleurodesis versus bedside chest tube and talc slurry. Two found in favour of VATS and one found no difference between the two groups. Tan et al[40] found a relative risk (RR) of 0.21 (95% CI 0.05 – 0.93) if VATS was employed and Shaw et al[1] a RR of 1.19 (95% CI 1.04 to 1.36) if bedside chest tube and talc slurry were employed. Shaw also reported data for mortality based on four studies and 127 patients comparing thoracoscopic versus bedside instillation of various sclerosant. There was no difference in mortality amongst the participants with RR = 1.36 (95% CI 0.88 to 2.10). Unfortunately neither meta analysis included the results of the largest RCT to date.[27]

Mummadi et al had a RR of 1.06 (95% CI 0.99 to 1.14) when comparing talc slurry to talc insufflation. Respiratory complications were less in the talc insufflation groups with a RR of 1.91 (95% CI 1.24 to 2.93).[41] VATS has the advantage of assessing the likelihood of adequate re expansion to achieve talc pleurodesis and failing this may facilitate the intra operative decision to decorticate or more likely place a long term catheter. The procedure is performed under sterile conditions, with general anaesthesia and peri operative pain service support. This compares favourably from the patient’s perspective to bedside insertion of tube under local anaesthetic.[39] Further, tissue biopsy provides histological confirmation and potentially molecular information, which may be important to ongoing management.

Likely increased cost (though no study has addressed the impact of repeat procedures in failed pleurodesis), pressure on operating theatre time and requirement of admission are disadvantages when compared to long term indwelling catheters, which may be inserted in an outpatient setting. Disadvantages of long term indwelling catheters include patient preference, long term consumable expense and requirement for long term nursing support.

Basso et al studied 46 patients undergoing Videoassisted thoracoscopic talc pleurodesis to assess improvement in quality of life in symptomatic malignant pleural effusions. Karnofsky Index and MRC dyspnoea score were both significantly improved post-operateively, p=0.014 and p<0.001 respectively.[42]

Efficacy and Safety of Thoracoscopic Talc Pleurodesis

A case series by Chen et al assessed the safety and efficacy of thoracocopic talc pleurodesis for different malignancies. There is no difference in pleurodesis success rate amongst difference tumour types or difference pathological classification of lung cancer. Adding negative pressure to chest tube drainage did not significantly impact on pleurodesis success. 68% of patients reported chest pain, 47% reported fevers and 0.28% developed pulmonary oedema. [43]

VATS decortication versus VATS pleurodesis

VATS decortication has not been the subject of a RCT, but mortality has been as high as 13% and prolonged air leak 20% in case series.[40]

Use of single incision thoracoscopic pleurectomy

A case series involving 19 patients undergoing single incision pleurectomy demonstrated a success rate of 91.4%. Median chest tube removal time was 2 days.{{Cite footnote|Citation:Kara M, Alzafer S, Okur E, Halezeroglu S 2013}

Intubated vs nonintubated VATS pleurodesis

There is no difference in pleurodesis success rate between intubated nonintubtaed VATS pleurodesis. Operating time, postoperative hospital stay, postoperative mortality, costs and quality of life were all better in the nonintubated VATS pleurodesis group. There is no difference in effusion free and overall survival.[44]

VATS talc pleurodesis versus tunnelled pleural catheter

Tunnelled pleural catheter has a significantly shorter mean length of stay (7 days vs 8 days, p=0.006), post procedure length of stay (3 days vs 6 days, p<0.0001) and less reinterventions required (1 vs 8, p=0.01) compared to VATS talc pleurodesis. There is no difference in complications, readmission for ipsilateral effusion or in-hospital mortality.[45]

Optimal choice of sclerosant

Over time, a large number of sclerosants have been used to achieve pleurodesis. Those commonly used in Australia have included formulations of bleomycin and tetracycline (that are no longer available) and talc. Success rates with bleomycin and tetracycline were 50-60%.[46] A 2013 study in Japan, demonstrated the efficacy of thoracocsocpic talc poudrage to be 100% at 180 days post procedure, and 71.1% in patients having talc slurry pleurodesis.[47] A 2014 case series, demonstrated a successful talc pleurodesis in 96% of patients.[48] Graded talc is used in almost all pleurodesis procedures in Australia whether by VATS or talc slurry. Only talc that is graded so that fine particles are excluded should be used as ungraded talc is associated with acute respiratory events that can be severe.[49] Justification for the use of talc as preferred sclerosant is derived from a meta-analysis that compared the relative efficacy of six sclerosants (talc, bleomycin, tetracyclines, corynebacterium parvum, mitozantrone, mepacrine) for pleurodesis. Particular emphasis was placed on talc, bleomycin and tetracycline as these sclerosants are most frequently used in clinical practice and were also the most extensively evaluated in these RCTs. The meta-analysis demonstrated that talc was the most effective sclerosant, with a relative risk for success of pleurodesis of 1.34 (95%CI 1.16 to 1.55). The efficacy of talc relative to bleomycin and tetracycline favoured talc as the sclerosant for successful pleurodesis (RR 1.23, 95%CI 1.00 to 1.50). Talc, compared with all other sclerosants as controls, had a number needed to benefit (NNTB) of 5 (95% CI 3.31 to 9.71).[1]

A meta-analysis of talc pleurodesis demonstrated a RR of 1.21 (95% CI 1.01 to 1.45) for talc pleurodesis compared to control. For thoracoscopic talc poudrage versus control the RR was 1.74 (95% CI 1.11 to 2.73) and talc slurry versus control the RR was 1.05 (95% CI 0.87 to 1.27). Talc was superior to bleomycin for pleurodesis (RR 1.25, 95% CI 1.06 to 1.46).[50] A Network Analysis to review the effectiveness of different methods of pleurodesis confirmed talc poudrage is a more effective method of pleurodesis, with no significant differences between other methods.[51]

A systematic review of six observational trials supports Iodopovidone as a safe and effective pleurodesis agent with the success rate of pleurodesis varying from 64.2% to 100%.The summary success rate of all the studies was 90.6% (95% confidence intervals [CI], 86.4–93.8). The only significant complication reported was chest pain of varying degree.[52] A randomised controlled trial consisting of 60 patients, investigating the adverse events of Iodopovidone demonstrated 47 serious events in 34 patients. These were mainly chest pain and hypertension.[53] In a case series by Godazandeh et al, pleurodesis success with povidone-iodone was 72.2%, with pain being the most common adverse event (35.9%).[54] In other parts of the world, small volume solutions of povidone-iodine have been used and achieve success rates similar to talc.[52][55][56] Iodopovidone is effective when administered via thoracoscopy or intercostal catheter. Only small volumes of iodine as reported in published papers should be used, as iodine toxicity can occur with larger instillations (up to 500mls).[52]

A randomised controlled trial comparing autologous blood pleurodeis to tetracycline pleurodesis in malignant pleural effusion demonstrated equivalent efficacy (83.4% vs 87.5%, p=0.37). Autologous blood pleurodesis had fewer complications (pain score p<0.01 and fever p<0.01). Total hospital stay was shorter in the autologous blood pleurodesis group (8.2 days vs 9.8 days, p=0.04).[57]

Gaafar et al performed a randomised controlled trial compared mistletoe preparation to Bleomycin as palliative treatment for malignant pleural effusion. There was no difference in clinical response (61.5% vs 30%, p=0.2138) or toxicities.([58] A case series using mistletoe extract demonstrated complete response in 79.03%, with an overall response rate of 96.77%. It was well tolerated with 80.7% of patients having no complications. The most frequent adverse events were gastrointestinal disorders.[59]

A case series by Menna et al using silver nitrate as a sclerosant following failed thoracoscopic talc poudrage showed a significant reduction in fluid drainage with no difference in hospital stay.[60] Adverse events are predominantly metabolic and hypoxia.[61]

Ogunrombi et al compared the efficacy of Povidone-iodine to Cyclophosphamide for pleurodesis. At 1 month, complete response in the Cyclophosphamide group was 76.4% vs 41.16%, and partial response 11.76% vs 47.06%.[62]

Vandetanib, a vascular endothelial growth factor inhibitor, was combined with an intrapleural catheter by Massarelli et al to determine whether this reduces time to pleurodesis.[63] They did not find any significant reduction to time in pleurodesis. In a Propensity Matched comparison between OK-432 and talc slurry pleurodesis, there was no difference in 30 day success (p=0.594), 90 day success (p=0.537) or adverse events (p=0.084).[64]

A pilot study using Mitoxantrone for pleurodesis, demonstrated complete pleurodesis responses of 17.6%, 7.7% and 0% at 1 month, 2 month and 3 month respectively. Partial response were 70.6%, 46.2% and 45.5% at 1 month, 2 months and 3 months respectively.[65]

Intrapleural hyperthermic perfusion chemotherapy versus talc pleurodesis or pleurectomy/decortication

The median survival is longer in patients undergoing Intrapleural hyperthermic perfusion chemotherapy compared to talc pleurodesis and pleurectomy/decortication (median survival 15 months vs 6 months vs 8 months). There was no significant difference in adverse events.[66]

A case series investigating simple intrapleural hyperthermia, demonstrated a complete response of 55.9%, a partial reponse of 26.5% and no response in 17.6%. Recurrence-free survival was 86.9%, 82.9% and 73.7% at 3 months, 4 months and 6 months respectively.[67]

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Radiofrequency ablation for malignant pleural effusion and/or pleural dissemination

Liu et al, evaluated radiofrequency ablation (RFA) combined with palliative thoracoscopic pleurodesis (TP) for malignant pleural effusion and/or pleurally disseminated non-small cell lung cancer. Progression-free survival at 1 year, 2 year and 3 years were 77.5% vs 64.3%, 41.4% vs 15% and 27.6% vs 0% in the RFA vs TP groups respectively. Median survival was 24 months in RFA group vs 18 months in the TP group (p=0.03). There was no difference in hospitalisation time (7 days in both groups).[68]

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Evidence summary and recommendations

Evidence summary Level References
Talc slurry or povidone-iodone solution may be instilled using a small bore 12-14F catheter.

Last reviewed January 2017

II, III-1, III-3 [32], [33], [34], [30]
Small bore chest tubes are associated with higher pleurodesis failure than large bore chest tubes.

Last reviewed January 2017

II [35]
Evidence-based recommendationQuestion mark transparent.png Grade
Consider using larger bore intercostal catheters for bedside pleurodesis, however smaller-bore, 12-14F, intercostal catheters may be used for bedside pleurodesis in patients with malignant pleural effusions.

Last reviewed January 2017

B


Evidence summary Level References
Indwelling pleural catheters reduce hospital length of stay, improve quality of life and provide superior effusion control to bedside pleurodesis.

Last reviewed January 2017

I, II, III-2, IV [12], [15], [20], [16], [45], [17], [37], [22]
Evidence-based recommendationQuestion mark transparent.png Grade
Indwelling pleural catheters might be effective in the outpatient management of malignant pleural effusion.

Last reviewed January 2017

C


Evidence summary Level References
In Haematological malignancies, indwelling pleural catheters may be used for recurrent malignant pleural effusions.

Last reviewed January 2017

IV [21]
Evidence-based recommendationQuestion mark transparent.png Grade
Consider the use of an Indwelling pleural catheter in malignant pleural effusion caused by Haematological malignancies

Last reviewed January 2017

D


Evidence summary Level References
In patients with NSCLC, VATS talc pleurodesis under general anesthesia is superior to bed side chest tube talc pleurodesis in terms of radiological recurrence.

Last reviewed January 2017

I, II [1], [26], [40]
VATS talc pleurodesis under general anesthesia is superior to bed side chest tube talc pleurodesis in terms of patient perception of pain, comfort and safety.

Last reviewed January 2017

II [26]
Evidence-based recommendationQuestion mark transparent.png Grade
VATS talc pleurodesis is recommended in fit (ECOG 0-2) patients with NSCLC with an expected survival of >2 months who have >90% lung expansion after needle thoracocentesis.

Last reviewed January 2017

A
Evidence-based recommendationQuestion mark transparent.png Grade
VATS talc pleurodesis may be considered in fit (ECOG 0-2) patients with NSCLC with an expected survival of >2 months who have <90% lung expansion after needle thoracocentesis.

VATS with biopsy and subsequent talc pleurodesis may be considered in patients who require pathological confirmation of their cancer to determine management.
Last reviewed January 2017

C


Evidence summary Level References
Cytoreductive therapy with intrapleural hyperthermic perfusion chemotherapy improves survival in patients with malignant pleural effusions.

Last reviewed January 2017

II, IV [1], [24], [25], [26], [27], [55], [66], [67]
Evidence-based recommendationQuestion mark transparent.png Grade
Intrapleural Hyperthermic Perfusion Chemotherapy (HIPEC) could be used in the treatment of malignant pleural effusions.

Last reviewed January 2017

C


Evidence summary Level References
Pleurodesis using an intercostal catheter and injection of sclerosant is an effective and safe alternative to VATS procedures albeit with a somewhat lower success rate.

Last reviewed January 2017

I, II, III-3, IV [13], [53], [41], [50], [1], [24], [25], [26], [27], [55], [48]
Evidence-based recommendationQuestion mark transparent.png Grade
Intercostal catheter (ICC) pleurodesis should be performed in patients unfit for more aggressive interventions and is an acceptable alternative where access to VATS without delay is problematic.

Last reviewed January 2017

A


Evidence summary Level References
The addition of radiofrequency ablation with palliative thoracoscopic pleurodesis for malignant pleural effusion and/or pleural NSCLC improves 3 years survival with significantly improved overall survival and the same hospitalisation time.

Last reviewed January 2017

III-2 [68]
Evidence-based recommendationQuestion mark transparent.png Grade
Consider the use of radiofrequency ablation in addition to thoracoscopic pleurodesis in MPE from NSCLC for improved survival.

Last reviewed January 2017

D



Practice pointQuestion mark transparent.png

If attempting a talc slurry pleurdodesis, consider using a large-bore intercostal catheter (24F) over a small-bore intercostal catheter (12-14F).
Last reviewed January 2017


Practice pointQuestion mark transparent.png

For fit patients, with an established diagnosis, an attempt to reduce pleural fluid re-accumulation by pleurodesis can be made at the first opportunity.
Last reviewed January 2017


Practice pointQuestion mark transparent.png

Initial drainage of MPE to dryness is a reasonable approach, as it may stratify patients to further treatment based on: a. radiological evidence of re expansion versus trapped lung, b. symptomatic improvement, and c. cytological confirmation of the diagnosis.
Last reviewed January 2017


Practice pointQuestion mark transparent.png

Tunnelled pleural catheters (TPC) may be preferred where lung reinflation is not achieved, but consideration of the practicalities of ongoing care should be made before their use.
Last reviewed January 2017


Practice pointQuestion mark transparent.png

Tunnelled pleural catheters may be considered in patients well enough for only a minor procedure where issues of disposable equipment costs can be addressed and ongoing clinical care is available.
Last reviewed January 2017


Practice pointQuestion mark transparent.png

Long term pleural catheter may be an option in those patients who prefer this.
Last reviewed January 2017


Practice pointQuestion mark transparent.png

In highly selected cases where re expansion is poor and patients adamantly refuse long term drainage, or alternatively have minimal symptomatic relief with drainage, it may be reasonable to attempt VATS decortication.
Last reviewed January 2017


Practice pointQuestion mark transparent.png

VATS decortication cannot be justified in patients with symptomatic relief from long term catheter drainage despite poor lung expansion.
Last reviewed January 2017


Practice pointQuestion mark transparent.png

Insertion of a small intercostal catheter is not without risk. In particular, standard dilators are long enough to damage major mediastinal structures if inserted an unnecessary distance into the thoracic cavity.
Last reviewed January 2017


Practice pointQuestion mark transparent.png

Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) are noninferior to opiates for pleurodesis failure, although more rescue analgesia is required
Last reviewed January 2017

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Shaw P, Agarwal R. Pleurodesis for malignant pleural effusions. Cochrane Database Syst Rev 2004;(1):CD002916 Available from: http://www.ncbi.nlm.nih.gov/pubmed/14973997.
  2. ↑ Estenne M, Yernault JC, De Troyer A. Mechanism of relief of dyspnea after thoracocentesis in patients with large pleural effusions. Am J Med 1983 May;74(5):813-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/6837605.
  3. ↑ Wang JS, Tseng CH. Changes in pulmonary mechanics and gas exchange after thoracentesis on patients with inversion of a hemidiaphragm secondary to large pleural effusion. Chest 1995 Jun;107(6):1610-4 Available from: http://www.ncbi.nlm.nih.gov/pubmed/7781355.
  4. ↑ Roberts ME, Neville E, Berrisford RG, Antunes G, Ali NJ, BTS Pleural Disease Guideline Group. Management of a malignant pleural effusion: British Thoracic Society Pleural Disease Guideline 2010. Thorax 2010 Aug;65 Suppl 2:ii32-40 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20696691.
  5. ↑ Korsic M, Badovinac S, Cucevic B, Janevski Z. Talc pleurodesis improves survival of patients with malignant pleural effusions: case-control study. Wien Klin Wochenschr 2015 Dec;127(23-24):963-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25860847.
  6. ↑ Puri V, Pyrdeck TL, Crabtree TD, Kreisel D, Krupnick AS, Colditz GA, et al. Treatment of malignant pleural effusion: a cost-effectiveness analysis. Ann Thorac Surg 2012 Aug;94(2):374-9; discussion 379-80 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22579398.
  7. ↑ Verma A, Chopra A, Lee YW, Bharwani LD, Asmat AB, Dokeu Basheer AA, et al. Can EGFR-Tyrosine Kinase Inhibitors (TKI) Alone Without Talc Pleurodesis Prevent Recurrence of Malignant Pleural Effusion (MPE) in Lung Adenocarcinoma. Curr Drug Discov Technol 2016 May 24 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27216707.
  8. ↑ Musani AI, Haas AR, Seijo L, Wilby M, Sterman DH. Outpatient management of malignant pleural effusions with small-bore, tunneled pleural catheters. Respiration 2004;71(6):559-66 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15627865.
  9. ↑ Thornton RH, Miller Z, Covey AM, Brody L, Sofocleous CT, Solomon SB, et al. Tunneled pleural catheters for treatment of recurrent malignant pleural effusion following failed pleurodesis. J Vasc Interv Radiol 2010 May;21(5):696-700 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20307992.
  10. ↑ Tremblay A, Michaud G. Single-center experience with 250 tunnelled pleural catheter insertions for malignant pleural effusion. Chest 2006 Feb;129(2):362-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16478853.
  11. ↑ Suzuki K, Servais EL, Rizk NP, Solomon SB, Sima CS, Park BJ, et al. Palliation and Pleurodesis in Malignant Pleural Effusion: The Role for Tunneled Pleural Catheters. J Thorac Oncol 2011 Feb 15 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21325982.
  12. ↑ 12.0 12.1 Bertolaccini L, Viti A, Gorla A, Terzi A. Home-management of malignant pleural effusion with an indwelling pleural catheter: ten years experience. Eur J Surg Oncol 2012 Dec;38(12):1161-4 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22959168.
  13. ↑ 13.0 13.1 Ahmed L, Ip H, Rao D, Patel N, Noorzad F. Talc pleurodesis through indwelling pleural catheters for malignant pleural effusions: retrospective case series of a novel clinical pathway. Chest 2014 Dec;146(6):e190-4 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25451360.
  14. ↑ Olden AM, Holloway R. Treatment of malignant pleural effusion: PleuRx catheter or talc pleurodesis? A cost-effectiveness analysis. J Palliat Med 2010 Jan;13(1):59-65 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19839739.
  15. ↑ 15.0 15.1 Demmy TL, Gu L, Burkhalter JE, Toloza EM, D'Amico TA, Sutherland S, et al. Optimal management of malignant pleural effusions (results of CALGB 30102). J Natl Compr Canc Netw 2012 Aug;10(8):975-82 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22878823.
  16. ↑ 16.0 16.1 Fysh ET, Waterer GW, Kendall PA, Bremmer PR, Dina S, Geelhoed E, et al. Indwelling pleural catheters reduce inpatient days over pleurodesis for malignant pleural effusion. Chest 2012 Aug;142(2):394-400 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22406960.
  17. ↑ 17.0 17.1 Lorenzo MJ, Modesto M, Pérez J, Bollo E, Cordovilla R, Muñoz M, et al. Quality-of-Life assessment in malignant pleural effusion treated with indwelling pleural catheter: a prospective study. Palliat Med 2014 Apr;28(4):326-34 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24523284.
  18. ↑ Boujaoude Z, Bartter T, Abboud M, Pratter M, Abouzgheib W. Pleuroscopic Pleurodesis Combined With Tunneled Pleural Catheter for Management of Malignant Pleural Effusion: A Prospective Observational Study. J Bronchology Interv Pulmonol 2015 Jul;22(3):237-43 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26165894.
  19. ↑ Reddy C, Ernst A, Lamb C, Feller-Kopman D. Rapid pleurodesis for malignant pleural effusions: a pilot study. Chest 2011 Jun;139(6):1419-23 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20930006.
  20. ↑ 20.0 20.1 Freeman RK, Ascioti AJ, Mahidhara RS. A propensity-matched comparison of pleurodesis or tunneled pleural catheter in patients undergoing diagnostic thoracoscopy for malignancy. Ann Thorac Surg 2013 Jul;96(1):259-63: discussion 263-4 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23673067.
  21. ↑ 21.0 21.1 Gilbert CR, Lee HJ, Skalski JH, Maldonado F, Wahidi M, Choi PJ, et al. The Use of Indwelling Tunneled Pleural Catheters for Recurrent Pleural Effusions in Patients With Hematologic Malignancies: A Multicenter Study. Chest 2015 Sep;148(3):752-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25789576.
  22. ↑ 22.0 22.1 Kheir F, Shawwa K, Alokla K, Omballi M, Alraiyes AH. Tunneled Pleural Catheter for the Treatment of Malignant Pleural Effusion: A Systematic Review and Meta-analysis. Am J Ther 2016;2016 Nov Dec;23(6):e1300-e1306 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25654292.
  23. ↑ Saydam O, Karapinar K, Gokce M, Kilic L, Metin M, Oz II, et al. The palliative treatment with intrapleural streptokinase in patients with multiloculated malignant pleural effusion: a double-blind, placebo-controlled, randomized study. Med Oncol 2015 May;32(6):612 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25958101.
  24. ↑ 24.0 24.1 24.2 Goodman A, Davies CW. Efficacy of short-term versus long-term chest tube drainage following talc slurry pleurodesis in patients with malignant pleural effusions: a randomised trial. Lung Cancer 2006 Oct;54(1):51-5 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16920219.
  25. ↑ 25.0 25.1 25.2 Cardillo G, Facciolo F, Carbone L, Regal M, Corzani F, Ricci A, et al. Long-term follow-up of video-assisted talc pleurodesis in malignant recurrent pleural effusions. Eur J Cardiothorac Surg 2002 Feb;21(2):302-5; discussion 305-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11825740.
  26. ↑ 26.0 26.1 26.2 26.3 26.4 26.5 Dresler CM, Olak J, Herndon JE 2nd, Richards WG, Scalzetti E, Fleishman SB, et al. Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion. Chest 2005 Mar;127(3):909-15 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15764775.
  27. ↑ 27.0 27.1 27.2 27.3 Stefani A, Natali P, Casali C, Morandi U. Talc poudrage versus talc slurry in the treatment of malignant pleural effusion. A prospective comparative study. Eur J Cardiothorac Surg 2006 Dec;30(6):827-32 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17113008.
  28. ↑ Havelock T, Teoh R, Laws D, Gleeson F, BTS Pleural Disease Guideline Group. Pleural procedures and thoracic ultrasound: British Thoracic Society Pleural Disease Guideline 2010. Thorax 2010 Aug;65 Suppl 2:ii61-76 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20696688.
  29. ↑ Özkul S, Turna A, Demirkaya A, Aksoy B, Kaynak K. Rapid pleurodesis is an outpatient alternative in patients with malignant pleural effusions: a prospective randomized controlled trial. J Thorac Dis 2014 Dec;6(12):1731-5 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25589966.
  30. ↑ 30.0 30.1 30.2 Wajda A, Engström H, Persson HL. Medical talc pleurodesis: which patient with cancer benefits least? J Palliat Med 2014 Jul;17(7):822-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24885834.
  31. ↑ Keeling AN, Leong S, Logan PM, Lee MJ. Empyema and effusion: outcome of image-guided small-bore catheter drainage. Cardiovasc Intervent Radiol ;31(1):135-41 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17943347.
  32. ↑ 32.0 32.1 Parulekar W, Di Primio G, Matzinger F, Dennie C, Bociek G. Use of small-bore vs large-bore chest tubes for treatment of malignant pleural effusions. Chest 2001 Jul;120(1):19-25 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11451810.
  33. ↑ 33.0 33.1 Caglayan B, Torun E, Turan D, Fidan A, Gemici C, Sarac G, et al. Efficacy of iodopovidone pleurodesis and comparison of small-bore catheter versus large-bore chest tube. Ann Surg Oncol 2008 Sep;15(9):2594-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18594928.
  34. ↑ 34.0 34.1 Clementsen P, Evald T, Grode G, Hansen M, Krag Jacobsen G, Faurschou P. Treatment of malignant pleural effusion: pleurodesis using a small percutaneous catheter. A prospective randomized study. Respir Med 1998 Mar;92(3):593-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9692129.
  35. ↑ 35.0 35.1 Rahman NM, Pepperell J, Rehal S, Saba T, Tang A, Ali N, et al. Effect of Opioids vs NSAIDs and Larger vs Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients With Malignant Pleural Effusion: The TIME1 Randomized Clinical Trial. JAMA 2015 Dec;314(24):2641-53 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26720026.
  36. ↑ Ghoneim A, Elkomy H, Elshora A, Mehrez M. Usefulness of pigtail catheter in pleurodesis of malignant pleural effusion. Egyptian Journal of Chest Diseases and Tuberculosis 2014;63:107-112.
  37. ↑ 37.0 37.1 Srour N, Amjadi K, Forster A, Aaron S. Management of malignant pleural effusions with indwelling pleural catheters or talc pleurodesis. Can Respir J 2013 Mar;20(2):106-10 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23616967.
  38. ↑ Terra RM, Junqueira JJ, Teixeira LR, Vargas FS, Pêgo-Fernandes PM, Jatene FB. Is full postpleurodesis lung expansion a determinant of a successful outcome after talc pleurodesis? Chest 2009 Aug;136(2):361-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19349389.
  39. ↑ 39.0 39.1 Yim AP, Chan AT, Lee TW, Wan IY, Ho JK. Thoracoscopic talc insufflation versus talc slurry for symptomatic malignant pleural effusion. Ann Thorac Surg 1996 Dec;62(6):1655-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8957368.
  40. ↑ 40.0 40.1 40.2 Tan C, Sedrakyan A, Browne J, Swift S, Treasure T. The evidence on the effectiveness of management for malignant pleural effusion: a systematic review. Eur J Cardiothorac Surg 2006 May;29(5):829-38 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16626967.
  41. ↑ 41.0 41.1 Mummadi S, Kumbam A, Hahn PY. Malignant pleural effusions and the role of talc poudrage and talc slurry: a systematic review and meta-analysis. F1000Res 2014;3:254 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25878773.
  42. ↑ Basso SM, Mazza F, Marzano B, Santeufemia DA, Chiara GB, Lumachi F. Improved quality of life in patients with malignant pleural effusion following videoassisted thoracoscopic talc pleurodesis. Preliminary results. Anticancer Res 2012 Nov;32(11):5131-4 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23155293.
  43. ↑ Chen J, Li Z, Xu N, Zhang X, Wang Y, Lin D. Efficacy of medical thoracoscopic talc pleurodesis in malignant pleural effusion caused by different types of tumors and different pathological classifications of lung cancer. Int J Clin Exp Med 2015 Oct 15;8(10):18945-53 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26770519.
  44. ↑ Mineo TC, Sellitri F, Tacconi F, Ambrogi V. Quality of life and outcomes after nonintubated versus intubated video-thoracoscopic pleurodesis for malignant pleural effusion: comparison by a case-matched study. J Palliat Med 2014 Jul;17(7):761-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24773212.
  45. ↑ 45.0 45.1 Hunt BM, Farivar AS, Vallières E, Louie BE, Aye RW, Flores EE, et al. Thoracoscopic talc versus tunneled pleural catheters for palliation of malignant pleural effusions. Ann Thorac Surg 2012 Oct;94(4):1053-7; discussion 1057-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22513274.
  46. ↑ Martínez-Moragón E, Aparicio J, Rogado MC, Sanchis J, Sanchis F, Gil-Suay V. Pleurodesis in malignant pleural effusions: a randomized study of tetracycline versus bleomycin. Eur Respir J 1997 Oct;10(10):2380-3 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9387969.
  47. ↑ Inoue T, Ishida A, Nakamura M, Nishine H, Mineshita M, Miyazawa T. Talc pleurodesis for the management of malignant pleural effusions in Japan. Intern Med 2013;52(11):1173-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23728550.
  48. ↑ 48.0 48.1 Ramić N, Krdžalić G, Mušanović N, Konjić F, Umihanić S, Ramić S, et al. Talc pleurodesis in pleuropulmonary diseases treatment. Med Glas (Zenica) 2014 Aug;11(2):264-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25082238.
  49. ↑ Campos JR, Werebe EC, Vargas FS, Jatene FB, Light RW. Respiratory failure due to insufflated talc. Lancet 1997 Jan 25;349(9047):251-2 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9014915.
  50. ↑ 50.0 50.1 Xia H, Wang XJ, Zhou Q, Shi HZ, Tong ZH. Efficacy and safety of talc pleurodesis for malignant pleural effusion: a meta-analysis. PLoS One 2014;9(1):e87060 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24475222.
  51. ↑ Clive AO, Jones HE, Bhatnagar R, Preston NJ, Maskell N. Interventions for the management of malignant pleural effusions: a network meta-analysis. Cochrane Database Syst Rev 2016 May 8;(5):CD010529 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27155783.
  52. ↑ 52.0 52.1 52.2 Agarwal R, Aggarwal AN, Gupta D, Jindal SK. Efficacy and safety of iodopovidone in chemical pleurodesis: a meta-analysis of observational studies. Respir Med 2006 Nov;100(11):2043-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16574389.
  53. ↑ 53.0 53.1 Andrade Neto JD, Terra RM, Teixeira RM, Pereira SV, Pego-Fernandes PM. Safety Profile of the Use of Iodopovidone for Pleurodesis in Patients with Malignant Pleural Effusion. Respiration 2015 Nov;90(5):369-75 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26439936.
  54. ↑ Godazandeh G, Qasemi NH, Saghafi M, Mortazian M, Tayebi P. Pleurodesis with povidone-iodine, as an effective procedure in management of patients with malignant pleural effusion. J Thorac Dis 2013 Apr;5(2):141-4 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23585939.
  55. ↑ 55.0 55.1 55.2 Mohsen TA, Zeid AA, Meshref M, Tawfeek N, Redmond K, Ananiadou OG, et al. Local iodine pleurodesis versus thoracoscopic talc insufflation in recurrent malignant pleural effusion: a prospective randomized control trial. Eur J Cardiothorac Surg 2011 Aug;40(2):282-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20961772.
  56. ↑ Olivares-Torres CA, Laniado-Laborín R, Chávez-García C, León-Gastelum C, Reyes-Escamilla A, Light RW. Iodopovidone pleurodesis for recurrent pleural effusions. Chest 2002 Aug;122(2):581-3 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12171835.
  57. ↑ Keeratichananont W, Limthon T, Keeratichananont S. Efficacy and safety profile of autologous blood versus tetracycline pleurodesis for malignant pleural effusion. Ther Adv Respir Dis 2015 Apr;9(2):42-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25663279.
  58. ↑ Gaafar R, Abdel Rahman AR, Aboulkasem F, El Bastawisy A. Mistletoe preparation (Viscum Fraxini-2) as palliative treatment for malignant pleural effusion: a feasibility study with comparison to bleomycin. Ecancermedicalscience 2014;8:424 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24834119.
  59. ↑ Cho JS, Na KJ, Lee Y, Kim YD, Ahn HY, Park CR, et al. Chemical Pleurodesis Using Mistletoe Extraction (ABNOVAviscum(®) Injection) for Malignant Pleural Effusion. Ann Thorac Cardiovasc Surg 2016;22(1):20-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26639937.
  60. ↑ Menna C, Andreetti C, Ibrahim M, Maurizi G, Poggi C, Barile R, et al. The effect of silver nitrate pleurodesis after a failed thoracoscopic talc poudrage. Biomed Res Int 2013;2013:295890 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24073398.
  61. ↑ Terra RM, Bellato RT, Teixeira LR, Chate RC, Pego-Fernandes PM. Safety and systemic consequences of pleurodesis with three different doses of silver nitrate in patients with malignant pleural effusion. Respiration 2015;89(4):276-83 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25823909.
  62. ↑ AB Ogunrombi, UU Onakpoya, U Ekrikpo, AS Aderibigbe, OA Aladesuru. Recurrence of Malignant Pleural Effusion Following Pleurodesis: Is There a Difference Between Use of Povidone-Iodine or Cyclophosphamide? Annals of African Surgery 2014 Jul Available from: http://www.ajol.info/index.php/aas/article/view/114657.
  63. ↑ Massarelli E, Onn A, Marom EM, Alden CM, Liu DD, Tran HT, et al. Vandetanib and indwelling pleural catheter for non-small-cell lung cancer with recurrent malignant pleural effusion. Clin Lung Cancer 2014 Sep;15(5):379-86 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24913066.
  64. ↑ Nohara K, Takada K, Kojima E, Ninomiya K, Miyamatsu S, Shimizu T, et al. A propensity score-matched comparison of the efficacies of OK-432 and talc slurry for pleurodesis for malignant pleural effusion induced by lung adenocarcinoma. Respir Investig 2016 Sep;54(5):341-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27566382.
  65. ↑ Sreter KB, Jakopovic M, Janevski Z, Samarzija M, Zarogoulidis P, Kioumis I, et al. A pilot study-is there a role for mitoxantrone pleurodesis in the management of pleural effusion due to lung cancer? Ann Transl Med 2016 May;4(9):162 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27275475.
  66. ↑ 66.0 66.1 Işık AF, Sanlı M, Yılmaz M, Meteroğlu F, Dikensoy O, Sevinç A, et al. Intrapleural hyperthermic perfusion chemotherapy in subjects with metastatic pleural malignancies. Respir Med 2013 May;107(5):762-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23462236.
  67. ↑ 67.0 67.1 Moon Y, Kim KS, Park JK. Simple intrapleural hyperthermia at thoracoscopic exploration to treat malignant pleural effusion. J Cardiothorac Surg 2015 Oct 28;10:136 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26510956.
  68. ↑ 68.0 68.1 Liu B, Liu L, Hu M, Qian K, Li Y. Effect of percutaneous radiofrequency ablation after thoracoscopic pleurodesis for treating non-small cell lung cancer patients with malignant pleural effusion and/or pleural dissemination. Thorac Cancer 2016 Sep;7(5):549-555 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27766779.

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