Management of a malignant pleural effusion: British Thoracic Social club pleural disease guideline 2010

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  1. Mark East Roberts1,
  2. Edmund Neville2,
  3. Richard G Berrisford3,
  4. George Antunesiv,
  5. Nabeel J Alii
  6. on behalf of the BTS Pleural Illness Guideline Group
  1. 1Sherwood Wood Hospitals NHS Foundation Trust, UK
  2. 2Portsmouth Hospitals NHS Trust, Uk
  3. 3Royal Devon and Exeter NHS Trust, UK
  4. 4S Tees NHS Foundation Trust, United kingdom of great britain and northern ireland
  1. Correspondence to Dr Nabeel J Ali, Sherwood Forest Hospitals NHS Foundation Trust, Kingsmill Infirmary, Mansfield Route, Sutton in Ashfield NG17 4JL, UK; nabeel.ali{at}sfh-tr.nhs.united kingdom

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Introduction

The discovery of malignant cells in pleural fluid and/or parietal pleura signifies disseminated or advanced disease and a reduced life expectancy in patients with cancer.1 Median survival following diagnosis ranges from 3 to 12 months and is dependent on the phase and type of the underlying malignancy. The shortest survival fourth dimension is observed in malignant effusions secondary to lung cancer and the longest in ovarian cancer, while cancerous effusions due to an unknown main take an intermediate survival time.2–6 Historically, studies showed that median survival times in effusions due to carcinoma of the breast are 5–vi months. Nevertheless, more recent studies take suggested longer survival times of upwards to fifteen months.seven–10 A comparing of survival times in breast cancer effusions in published studies to 1994 calculated a median survival of 11 months.ix

Currently, lung cancer is the most common metastatic tumour to the pleura in men and breast cancer in women.4 xi Together, both malignancies business relationship for 50–65% of all cancerous effusions (table 1). Lymphomas, tumours of the genitourinary tract and alimentary canal account for a further 25%.2 12–14 Pleural effusions from an unknown primary are responsible for 7–15% of all malignant pleural effusions.3 13 14 Few studies have estimated the proportion of pleural effusions due to mesothelioma: studies from 1975, 1985 and 1987 identified mesothelioma in i/271, 3/472 and 22/592 patients, respectively, but in that location are no more recent information to update this in light of the increasing incidence of mesothelioma.4 13 xiv

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Table 1

Primary tumour site in patients with cancerous pleural effusion

Attempts have been made to predict survival based on the clinical characteristics of pleural fluid. None has shown a definite correlation: a recent systematic review of studies including 433 patients assessing the predictive value of pH ended that depression pH does not reliably predict a survival of <3 months.fifteen 16 In malignant mesothelioma, one study has shown an association betwixt increasing pH and increasing survival.17 Burrows et al showed that only functioning status was significantly associated with mortality: median survival was 1.ane months with a Karnofsky score <30 and 13.two months with a score >70.18

An algorithm for the management of malignant pleural effusions is shown in effigy 1.

Clinical presentation

  • The bulk of malignant effusions are symptomatic. (C)

  • Massive pleural effusions are most normally due to malignancy. (C)

The bulk of patients who nowadays with a malignant pleural effusion are symptomatic, although upwardly to 25% are asymptomatic with an incidental finding of effusion on physical examination or by chest radiography.ane Dyspnoea is the most mutual presenting symptom, reflecting reduced compliance of the chest wall, depression of the ipsilateral diaphragm, mediastinal shift and reduction in lung book.19 Breast pain is less mutual and is unremarkably related to malignant involvement of the parietal pleura, ribs and other intercostal structures. Constitutional symptoms including weight loss, malaise and anorexia generally accompany respiratory symptoms.

A massive pleural effusion is defined as consummate or almost complete opacification of a hemithorax on the chest x-ray. It is commonly symptomatic and is commonly associated with a malignant cause.20 The diagnosis of a malignant pleural effusion is discussed in the guideline on the investigation of a unilateral pleural effusion.

Management options

Treatment options for malignant pleural effusions are determined by several factors: symptoms and performance status of the patient, the master tumour type and its response to systemic therapy, and degree of lung re-expansion following pleural fluid evacuation. Although small jail cell lung cancer, lymphoma and breast cancer ordinarily answer to chemotherapy, associated secondary pleural effusions may require intervention during the grade of treatment (effigy 1). Malignant pleural effusions are often most effectively managed past complete drainage of the effusion and instillation of a sclerosant to promote pleurodesis and prevent recurrence of the effusion. Options for management include observation, therapeutic pleural aspiration, intercostal tube drainage and instillation of sclerosant, thoracoscopy and pleurodesis or placement of an indwelling pleural catheter.

Observation

  • Observation is recommended if the patient is asymptomatic and the tumour type is known. (C)

  • Advice should exist sought from the respiratory team and/or respiratory multidisciplinary squad for symptomatic cancerous effusions. (✓)

The majority of these patients volition become symptomatic in due grade and require further intervention. There is no evidence that initial thoracentesis carried out co-ordinate to standard techniques will reduce the chances of subsequent effective pleurodesis after tube drainage. However, repeated thoracentesis may limit the scope for thoracoscopic intervention every bit it oft leads to the germination of adhesions between the parietal and visceral pleura.

Therapeutic pleural aspiration

  • Pleural effusions treated by aspiration alone are associated with a high rate of recurrence of effusion at 1month so aspiration is not recommended if life expectancy is >icalendar month. (A)

  • Circumspection should exist taken if removing >1.vl on a single occasion. (C)

Repeated therapeutic pleural aspiration provides transient relief of symptoms and avoids hospitalisation for patients with limited survival expectancy and poor performance status. It is appropriate for delicate or terminally ill patients. However, as small-diameter chest tubes are widely available, constructive and may exist inserted with minimal discomfort,21–26 they may exist preferable. The amount of fluid evacuated past pleural aspiration will exist guided past patient symptoms (cough, chest discomfort)27 and should exist limited to 1.5 l on a single occasion. Pleural aspiration lone and intercostal tube drainage without instillation of a sclerosant are associated with a high recurrence rate and a small take chances of iatrogenic pneumothorax and empyema.28–36 Therapeutic pleural aspiration should have place under ultrasound guidance (see guideline on pleural procedures).

Intercostal tube drainage and intrapleural instillation of sclerosant

  • Other than in patients with a very brusk life expectancy, modest-diameter chest tubes followed by pleurodesis are preferable to recurrent aspiration. (✓)

  • Intercostal drainage should be followed by pleurodesis to foreclose recurrence unless lung is significantly trapped. (A)

Pleurodesis is idea to occur through a diffuse inflammatory reaction and local activation of the coagulation system with fibrin deposition.37 38 Increased pleural fibrinolytic activeness is associated with failure of pleurodesis, as is extensive tumour involvement of the pleura.39 40 Intercostal drainage without pleurodesis is associated with a high rate of effusion recurrence and should be avoided (see evidence table available on the BTS website at world wide web.brit-thoracic.org.uk). A suggested method for undertaking pleurodesis is shown in box 1.

Box ane How to perform talc slurry chemic pleurodesis

  • Insert pocket-size-bore intercostal tube (10–14 F).

  • Controlled evacuation of pleural fluid.

  • Confirm full lung re-expansion and position of intercostal tube with chest ten-ray. In cases where incomplete expansion occurs, run across text regarding trapped lung.

  • Administer premedication prior to pleurodesis (come across text).

  • Instill lidocaine solution (iii mg/kg; maximum 250 mg) into pleural space followed past 4-5 one thousand sterile graded talc in 50 ml 0.9% saline.

  • Clamp tube for ane-2 h.

  • Remove intercostal tube within 24-48 h.

In animals the effectiveness of pleurodesis may exist reduced by concomitant employ of corticosteroids. Recent evidence in rabbits has shown reduced pleural inflammatory reaction and, in some cases, prevention of pleurodesis with administration of corticosteroids at the time of talc pleurodesis.41 A subgroup analysis comparing the efficacy of pleurodesis in the presence and absence of non-randomised oral corticosteroid utilize also suggested a negative issue of corticosteroids on efficacy.42 The assistants of not-steroidal anti-inflammatory drugs (NSAIDs) at the time of pleurodesis is more contentious. Beast studies accept suggested that the use of NSAIDs may impair the activeness of pleurodesis agents, just there is no evidence from human studies.43

Size of intercostal tube

  • Small-bore (x–xiv F) intercostal catheters should be the initial choice for effusion drainage and pleurodesis. (A)

Conventional large-bore intercostal tubes (24–32 F) take been employed in near studies involving sclerosing agents.44 They accept traditionally been used because they are thought to be less prone to obstruction by fibrin plugs, but at that place is niggling published evidence to ostend this. The placement of large-bore tubes is perceived to be associated with pregnant discomfort45 and this has led to the cess of smaller bore tubes (10–fourteen F) for drainage and assistants of sclerosing agents.22 46 47 3 randomised trials investigating the difference in efficacy between minor- and large-diameter chest tubes all concluded that they were equivalent (run across evidence table available on the BTS website at www.brit-thoracic.org.united kingdom).21–23 Studies using small-bore intercostal tubes with commonly used sclerosants have reported similar success rates to big-bore tubes and appear to cause less discomfort.24–26 48 The small-scale-bore tubes in these studies were inserted either at the patient's bedside by a doctor or under radiological guidance.

Small-bore tubes take been used for ambulatory or outpatient pleurodesis. Patz and colleagues used a fluoroscopically-placed tube (10 F) connected to a airtight gravity drainage purse system for this purpose.49 Bleomycin was the preferred sclerosing agent and the pleurodesis success rate approached 80%. Ambulatory drainage is discussed further in the department on indwelling pleural catheters.

Fluid drainage, pleurodesis and trapped lung

  • Large pleural effusions should be tuckered in a controlled manner to reduce the risk of re-expansion pulmonary oedema. (C)

  • In patients where merely partial pleural apposition tin be achieved, chemical pleurodesis may still be attempted and may provide symptomatic relief. (B)

  • In symptomatic cases where pleural apposition cannot exist achieved ('trapped lung'), indwelling pleural catheters offer a more bonny therapeutic approach than recurrent aspiration. (✓)

  • In one case effusion drainage and lung re-expansion have been radiographically confirmed, pleurodesis should non exist delayed. (B)

  • Suction to assistance pleural drainage before and afterwards pleurodesis is usually unnecessary merely, if practical, a loftier-volume depression-pressure arrangement is recommended. (C)

Large pleural effusions should exist drained incrementally, draining a maximum of 1.5 l on the first occasion. Any remaining fluid should be drained 1.5 l at a time at ii h intervals, stopping if the patient develops chest discomfort, persistent coughing or vasovagal symptoms. Re-expansion pulmonary oedema is a well-described serious just rare complication following rapid expansion of a collapsed lung through evacuation of large amounts of pleural fluid on a single occasion and the employ of early on and excessive pleural suction.50 51 Putative pathophysiological mechanisms include reperfusion injury of the underlying hypoxic lung, increased capillary permeability and local production of neutrophil chemotactic factors such as interleukin-eight.52 53

The about of import requirement for successful pleurodesis is satisfactory apposition of the parietal and visceral pleura, confirmed radiologically.44 54 55 Incomplete lung re-expansion may exist due to a thick visceral peel ('trapped lung'), pleural loculations, proximal large airway obstruction or a persistent air leak. About studies indicate that the lack of a response post-obit instillation of a sclerosant is associated with incomplete lung expansion.56 Where complete lung re-expansion or pleural apposition is not achieved, pleurodesis may however be attempted or an indwelling pleural catheter may be inserted. Robinson and colleagues reported a favourable response in 9 out of 10 patients with fractional re-expansion of the lung in a study using doxycycline equally a sclerosing agent.57 The amount of trapped lung compatible with successful pleurodesis is unknown. Complete lack of pleural apposition will forestall pleurodesis: consideration of an indwelling pleural catheter is recommended in this situation. Where more than one-half the visceral pleura and parietal pleura are apposed, pleurodesis may be attempted although there are no studies to support this recommendation.

The corporeality of pleural fluid drained per day before the instillation of a sclerosant (<150 ml/twenty-four hour period) is less relevant for successful pleurodesis than radiographic confirmation of fluid evacuation and lung re-expansion. In a randomised study, a shorter menses of intercostal tube drainage and hospital stay was seen in the group in whom sclerotherapy was undertaken as soon as complete lung re-expansion was documented (majority <24 h) than in the group in whom pleurodesis was attempted but when the fluid drainage was <150 ml/day. The success rate in both groups approached eighty%.55 Afterwards sclerosant instillation, the duration of intercostal drainage appears not to touch on the chances of successful pleurodesis, although the only randomised study to address this question was underpowered.58

Suction may rarely exist required for incomplete lung expansion and a persistent air leak. When suction is practical, the use of high-volume depression-pressure systems is recommended with a gradual increment in pressure to near –20 cm HtwoO.

Analgesia and premedication

  • Lidocaine (threemg/kg; maximum 250mg) should be administered intrapleurally just prior to sclerosant administration. (B)

  • Premedication should be considered to convalesce anxiety and pain associated with pleurodesis. (C)

Intrapleural assistants of sclerosing agents may be painful; meaning pain is reported in 7% patients receiving talc to sixty% with historical agents such as doxycycline.57 59 Discomfort can exist reduced past administering local anaesthetic via the bleed prior to pleurodesis. Lidocaine is the most often studied local anaesthetic for intrapleural administration. The onset of activity of lidocaine is almost firsthand and it should therefore be administered just before the sclerosant. The maximum dose of lidocaine is 3 mg/kg (21 ml of a ane% lidocaine solution for a seventy kg male), with a ceiling of 250 mg. The issue of safety has been highlighted in 2 studies. Wooten et alsixty showed that the hateful meridian serum concentration of lidocaine following 150 mg of intrapleural lidocaine was 1.3 μg/ml, well below the serum concentration associated with central nervous system side effects (ie, >iii μg/ml). In an earlier study of 20 patients, larger doses of lidocaine were necessary to achieve acceptable levels of local anaesthesia. The patients receiving 250 mg lidocaine had more frequent pain-free episodes than those given 200 mg, while serum levels remained within the therapeutic range. Side furnishings were limited to transient paraesthesiae in a single patient.61 The reason for the significant difference in analgesia between the two groups with only a small increment in the lidocaine dose was unclear.

At that place are no studies to inform a recommendation on the employ of premedication and sedation in not-thoracoscopic pleurodesis. Pleurodesis is an uncomfortable process and is associated with anxiety for the patient. The use of sedation may be helpful to allay such fears and induce amnesia. The level of sedation should be appropriate to relieve anxiety simply sufficient to maintain patient interaction. Sedation employed before pleurodesis should be conducted with continuous monitoring with pulse oximetry and in a setting where resuscitation equipment is available.62 Further research is underway to address this issue.

Sclerosant and complications

  • Talc is the nearly effective sclerosant available for pleurodesis. (A)

  • Graded talc should always be used in preference to ungraded talc as it reduces the risk of arterial hypoxaemia complicating talc pleurodesis. (B)

  • Talc pleurodesis is as effective when administered equally a slurry or past insufflation. (B)

  • Bleomycin is an alternative sclerosant with a modest efficacy charge per unit. (B)

  • Pleuritic chest pain and fever are the most common side effects of sclerosant administration. (B)

An platonic sclerosing agent must possess several essential qualities: a high molecular weight and chemical polarity, low regional clearance, rapid systemic clearance, a steep dose-response curve and be well tolerated with minimal or no side effects. The pick of a sclerosing agent will be determined by the efficacy or success rate of the agent, accessibility, condom, ease of administration, number of administrations to achieve a consummate response and cost. Despite the evaluation of a broad variety of agents, to date no ideal sclerosing amanuensis exists.

Comparing of sclerosing agents is hampered past the lack of comparative randomised trials, different eligibility criteria and disparate criteria for measuring response and end points. A complete response is ordinarily defined as no reaccumulation of pleural fluid after pleurodesis until death, and a fractional response equally partial reaccumulation of fluid radiographically but not requiring further pleural intervention such as aspiration. However, some studies use a 30-day cut-off. A recent Cochrane review concluded that thoracoscopic talc pleurodesis is probably the optimal method for pleurodesis.63 This view is supported by a systematic review.64 Studies are presently underway investigating other agents including the profibrotic cytokine transforming growth factor β.

Tetracycline

Until recently, tetracycline had been the most popular and widely used sclerosing agent in the Uk. Unfortunately, parenteral tetracycline is no longer available for this indication in many countries equally its product has ceased.65

Sterile talc

Talc (MgthreeSi4O10(OH)2) is a trilayered magnesium silicate sheet that is inert and was commencement used as a sclerosing amanuensis in 1935.66 Talc used for intrapleural administration is asbestos-gratuitous and sterilised effectively by dry out heat exposure, ethylene oxide and gamma radiation. It may exist administered in two ways: at thoracoscopy using an atomiser termed 'talc poudrage' or via an intercostal tube in the course of a pause termed 'talc slurry'.

Success rates (complete and fractional response) for talc slurry range from 81% to 100%.30 54 56 67–70 The majority of studies take used talc slurry lone and only a limited number of comparative studies have been published (see evidence tabular array available on the BTS website at www.brit-thoracic.org.uk). A truncated randomised report by Lynch and colleagues71 compared talc slurry (five k) with bleomycin (60 000 units) and tetracycline (750 mg). Although the written report was terminated early on because of the removal of tetracycline from the U.s.a. market, analysis of the data to that indicate revealed no differences between the three treatment groups one month afterwards pleurodesis. In a randomised trial betwixt talc slurry (5 one thousand) and bleomycin (60 000 units), 90% of the talc grouping accomplished a complete response at 2 weeks compared with 79% of the bleomycin group, which was statistically insignificant.72 Three studies have directly compared talc slurry with talc poudrage (see evidence table available on the BTS website at world wide web.brit-thoracic.org.great britain).73–75 For 1 randomised study the data are available only in abstract class.73 It suggests superiority of poudrage over slurry, but express data are available to validate this conclusion. Of the other two studies, Stefani et al compared medical thoracoscopy and talc poudrage with talc slurry in a not-randomised style.75 Their results advise superiority of poudrage over slurry, but the two groups were not equal with respect to performance status. In the largest written report, Dresler et al compared a surgical arroyo to talc poudrage with talc slurry.74 They concluded equivalence, but 44% of patients dropped out of the study earlier the 30-day stop betoken due to deaths and a requirement of xc% lung re-expansion radiologically afterward intervention to be included in the analysis.

Three studies have compared talc poudrage with other agents administered via an intercostal tube. Ane compared bleomycin (see below) and the other two tetracyclines (encounter show table available on the BTS website at www.brit-thoracic.org.uk).76–78 Diacon et al ended that talc insufflation at medical thoracoscopy was superior to bleomycin instillation on efficacy and toll grounds.76 Kuzdzal et al and Fentiman et al both showed an advantage of talc insufflation over tetracyclines.77 78 Each of the three studies analysed fewer than 40 patients.

Talc slurry is usually well tolerated and pleuritic chest pain and mild fever are the most common side effects observed. A serious complication associated with the use of talc is adult respiratory distress syndrome or astute pneumonitis leading to astute respiratory failure. There have been many reports of pneumonitis associated with talc pleurodesis, although predominantly from the UK and the USA where historically non-graded talc has been used.56 79–87 The machinery of astute talc pneumonitis is unclear and has been reported with both talc poudrage and slurry. 56 eighty This complexity is related to the grade of talc used. Maskell and colleagues undertook two studies to determine this association. In the first study they randomised 20 patients to pleurodesis using either mixed talc or tetracycline and compared DTPA clearance in the contralateral lung with that undergoing pleurodesis at 48 h subsequently pleurodesis.88 DTPA clearance one-half time decreased by more in the talc grouping, which is a marking of increased lung inflammation. In that location was also a greater arterial desaturation in those patients exposed to talc. In the 2d office of the study, graded (particle size >15 μm) and non-graded (fifty% particle size <15 μm) talc were compared. There was a greater alveolar–arterial oxygen slope in the group exposed to non-graded talc at 48 h later on pleurodesis. In a subsequent cohort study of 558 patients who underwent thoracoscopic pleurodesis using graded talc, at that place were no episodes of pneumonitis.89

Two studies have investigated the systemic distribution of talc particles in rats afterwards talc pleurodesis. The earlier written report using uncalibrated talc found widespread organ deposition of talc particles in the lungs, eye, encephalon, spleen and kidneys at 48 h. The later study used calibrated talc and found liver and spleen degradation (but no lung deposition) at 72 h, but no evidence of pleurodesis in the treated lungs.ninety 91 A further study in rabbits constitute greater systemic distribution of talc with 'normal' (small-scale particle talc).92 This supports the show from clinical studies that big particle talc is preferable to small particle talc.

Bleomycin

Bleomycin is the most widely used antineoplastic amanuensis for the management of malignant pleural effusions. Its mechanism of activity is predominantly as a chemical sclerosant similar to talc and tetracycline. Although 45% of the administered bleomycin is captivated systemically, it has been shown to crusade minimal or no myelosuppression.93 Bleomycin is an effective sclerosant with success rates after a single administration ranging from 58% to 85% with a mean of 61%. No studies have demonstrated superiority over talc.42 71 72 94–102 It has an acceptable side effect profile with fever, breast pain and cough the nearly common agin effects.99 102 The recommended dose is 60 000 units mixed in normal saline. Bleomycin has also been used in studies evaluating small-bore intercostal tubes placed under radiological guidance with like efficacy rates.46 48 49 103 In the U.s.a., bleomycin is a more than expensive sclerosant than talc, only this is not the instance in Europe where non-proprietary formulations are available.42 72 104

Rotation following pleurodesis

  • Patient rotation is non necessary after intrapleural instillation of sclerosant. (A)

Rotation of the patient to achieve adequate distribution of the agent over the pleura has been described in many studies. Even so, rotating the patient is fourth dimension consuming, inconvenient and uncomfortable. A study using radiolabelled tetracycline showed that tetracycline is dispersed throughout the pleural space within seconds and rotation of the patient did non influence distribution.105 A subsequent randomised trial using tetracycline, minocycline and doxycycline revealed no significant divergence in the success rate of the process or elapsing of fluid drainage between the rotation and not-rotation groups.106 A similar study using talc showed no difference in distribution of talc after 1 min or one h and no difference in the success charge per unit of pleurodesis at 1 month.107

Clamping and removal of intercostal tube

  • The intercostal tube should exist clamped for 1 h later sclerosant administration. (C)

  • In the absence of excessive fluid drainage (>250 ml/ day) the intercostal tube should exist removed within 24–48 h of sclerosant administration. (C)

Clamping of the intercostal tube post-obit intrapleural administration of the sclerosant should be brief (i h) to prevent the sclerosant from immediately draining back out of the pleural space, although there are no studies to show that this is necessary.105 Intercostal tube removal has been recommended when fluid drainage is <150 ml/twenty-four hours, but in that location is piffling evidence to back up this activeness.58 68 108 109 In the simply randomised report that has addressed the consequence, Goodman and Davies randomised patients to 24 h versus 72 h drainage following talc slurry pleurodesis regardless of volume of fluid drainage. They found no departure in pleurodesis success, although they did not reach the recruitment target based upon the ability calculation. In the absence of any evidence that protracted drainage is beneficial, and given the discomfort associated with prolonged drainage, nosotros recommend removal of the intercostal tube inside 24–48 h after the instillation of the sclerosant, provided the lung remains fully re-expanded and there is satisfactory evacuation of pleural fluid on the chest x-ray.

Pleurodesis failure

The about likely cause of pleurodesis failure is the presence of trapped lung. At that place is no reliable fashion to predict pleurodesis failure: a recent systematic review found that an arbitrary cut-off of pH <7.20 did not predict pleurodesis failure.15 Where pleurodesis fails, there is no evidence available as to the nearly effective secondary procedure. Nosotros recommend that farther evacuation of pleural fluid should be attempted with either a repeat pleurodesis or insertion of indwelling pleural catheter, depending upon the presence of trapped lung. Surgical pleurectomy has been described as an culling choice for patients with mesothelioma (meet later).

Cancerous seeding at intercostal tube or port site

  • Patients with proven or suspected mesothelioma should receive prophylactic radiotherapy to the site of thoracoscopy, surgery or large-bore chest drain insertion, but at that place is little evidence to support this for pleural aspirations or pleural biopsy. (B)

Local neoplasm recurrence or seeding following diagnostic and therapeutic pleural aspiration, pleural biopsy, intercostal tube insertion and thoracoscopy is uncommon in non-mesothelioma malignant effusions.110–113 However, in mesothelioma upwardly to 40% of patients may develop cancerous seeding at the site of pleural procedures. Three randomised studies take addressed the efficacy of procedure site radiotherapy to prevent tract metastasis (see testify table available on the BTS website at www.brit-thoracic.org.uk).114–116 Boutin and colleagues114 constitute that local metastases were prevented in patients who received radiotherapy (21 Gy in iii fractions) to the site of thoracoscopy. All the patients received radiotherapy within 2 weeks of thoracoscopy. The incidence of tract metastases in the control group in this study was 40%. This report was followed past a longitudinal written report that supported its conclusions.117 In two subsequently studies including sites from a wider range of procedures such as needle biopsy and chest drain, the incidence of tract metastases was non significantly different. Bydder and colleagues showed no benefit of a single ten Gy radiotherapy fraction to the intervention site in preventing recurrence.116 All the patients received radiotherapy within fifteen days of the procedure, but 46% of procedures were fine needle aspirations. O'Rourke and colleagues used the aforementioned radiotherapy dose as Boutin just to smaller fields. They found no benefit of radiotherapy, just again included a range of procedures including needle biopsy. The report included threescore patients but just 16 thoracoscopies, seven in the radiotherapy group and 9 in the all-time supportive care group. Tract metastases occurred in 4 patients in the best supportive care group (a charge per unit of 44%) and none in the radiotherapy grouping.115 This is very similar to the incidence of tract metastasis in the report past Boutin et al (40%). The other procedures were pleural biopsies (45%) and chest tubes (25%). A longitudinal study by Agarwal et al found the highest charge per unit of pleural tract metastases in association with thoracoscopy (16%), thoracotomy (24%) and breast tube (9%), but a much lower rate in clan with pleural aspiration (3.6%) and image-guided biopsy (4.v%).118 Conscientious assay of the available data therefore supports the employ of radiotherapy to reduce tract metastasis later significant pleural instrumentation (thoracoscopy, surgery or large-diameter chest drain), only not for less invasive procedures such as pleural biopsy or pleural aspiration. A larger study to specifically address this question would be of use.

A cohort of 38 patients described by West et al reported an incidence of pleural tract metastasis subsequently radiotherapy of 5%, but in these cases the metastasis occurred at the edge of the radiotherapy field. Of 6 patients who received radiotherapy after an indwelling pleural catheter, ane subsequently developed pleural tract metastasis.119 There are, at present, bereft data on which to make a recommendation well-nigh the apply of radiotherapy in the presence of indwelling pleural catheters.

The part of condom radiotherapy following pleural procedures in non-mesothelioma malignant effusions has not been established and therefore cannot be recommended.

Intrapleural fibrinolytics

  • Intrapleural instillation of fibrinolytic drugs is recommended for the relief of lamentable dyspnoea due to multiloculated cancerous effusion resistant to simple drainage. (C)

The employ of fibrinolytic agents to meliorate symptoms related to complex pleural effusions has been described in several studies although there are no randomised controlled trials.

Davies et al found that intrapleural streptokinase increased pleural fluid drainage and led to radiographic improvement and amelioration of symptoms in 10 patients with multiloculated or septated malignant effusions. Intrapleural streptokinase was well tolerated and no allergic or haemorrhagic complications were reported.120 Gilkeson et al121 preferred urokinase in their prospective but non-randomised study. Twenty-two malignant pleural effusions were treated with urokinase resulting in a substantial increase in pleural fluid output in patients both with and without radiographic show of loculations. The majority then underwent pleurodesis with doxycycline resulting in a complete response rate of 56%. Similarly, no allergic or haemorrhagic complications were encountered. In the largest series, 48 patients unfit for surgical release of trapped lung subsequently incomplete lung re-expansion following tube drainage were given intrapleural urokinase.122 Breathlessness was improved in 29 patients, 27 of whom eventually successfully accomplished pleurodesis. This written report compared cases with historical controls treated solely with saline flushes and in whom breathlessness was not assessed.

None of these studies is large plenty to accurately depict the safe contour of fibrinolytic drugs in this setting. Immune-mediated or haemorrhagic complications have rarely been described with the administration of intrapleural fibrinolytics in contrast to systemic administration of these agents.123 124 A chest physician should be involved in the care of all patients receiving this handling.

Thoracoscopy

  • In patients with good performance status, thoracoscopy is recommended for diagnosis of suspected cancerous pleural effusion and for drainage and pleurodesis of a known cancerous pleural effusion. (B)

  • Thoracoscopic talc poudrage should be considered for the control of recurrent cancerous pleural effusion. (B)

  • Thoracoscopy is a safe process with low complexity rates. (B)

Thoracoscopy (nether sedation or general anaesthesia) has grown in popularity equally a diagnostic and therapeutic tool for malignant effusions. Under sedation, it is at present widely used by respiratory physicians in the diagnosis and direction of pleural effusions in patients with good functioning status.125–128 Patient selection for thoracoscopy and talc poudrage is important in view of the invasive nature of the procedure and cost.129 A significant benefit of thoracoscopy is the ability to obtain a diagnosis, bleed the effusion and perform a pleurodesis during the same procedure.

The diagnostic yield and accuracy of thoracoscopy for malignant effusions is >90%.99 125 127 130 131 Talc poudrage performed during thoracoscopy is an constructive method for controlling malignant effusions with a pleurodesis success charge per unit of 77–100%.half dozen 68 97 132–138 Randomised studies take established the superiority of talc poudrage over both bleomycin and tetracyclines (come across bear witness table available on the BTS website at world wide web.brit-thoracic.org.uk).73 76–78 1 large randomised study comparing talc poudrage with talc slurry failed to establish a deviation in efficacy betwixt the two techniques.74 A further modest not-randomised study comparing these two techniques too established equivalence.133 A large study has established the condom of talc poudrage using large particle talc; no cases of respiratory failure were seen in this cohort of 558 patients.89 Talc poudrage is known peculiarly to be constructive in the presence of effusions due to carcinoma of the chest.139

Thoracoscopy has less to offer in patients with a known malignant pleural effusion and a conspicuously trapped lung on the breast x-ray. Yet, under full general anaesthesia, reinflation of the lung nether thoracoscopic vision will inform whether the lung is indeed trapped and therefore guide the decision to perform talc poudrage or insert a pleural catheter. The procedure tin facilitate breaking up of loculations or blood clot in haemorrhagic malignant pleural effusion and can allow the release of adhesions and thereby assistance lung re-expansion and apposition of the pleura for talc poudrage.140 141

Thoracoscopy is a rubber and well-tolerated process with a low perioperative mortality charge per unit (<0.v%).six 126 129 142 The nearly common major complications are empyema and acute respiratory failure secondary to infection or re-expansion pulmonary oedema, although the latter may be avoided past staged evacuation of pleural fluid and allowing air to replace the fluid.127 129 143

Long-term ambulatory indwelling pleural catheter drainage

  • Convalescent indwelling pleural catheters are effective in controlling recurrent and symptomatic malignant effusions in selected patents. (B)

Insertion of a tunnelled pleural catheter is an culling method for decision-making recurrent and symptomatic malignant effusions including patients with trapped lung. Several catheters have been adult for this purpose and the published studies employing them have reported encouraging results.140 144–147 The presence of foreign fabric (silastic catheter) inside the pleural space stimulates an inflammatory reaction, and vacuum drainage bottles connected to the catheter every few days encourage re-expansion and obliteration of the pleural space. Most catheters can be removed after a relatively short menstruation.

In the only randomised and controlled study to date, Putnam and colleagues145 compared a long-term indwelling pleural catheter with doxycycline pleurodesis via a standard intercostal tube. The length of hospitalisation for the indwelling catheter group was significantly shorter (1 mean solar day) than that of the doxycycline pleurodesis group (6 days). Spontaneous pleurodesis was achieved in 42 of the 91 patients in the indwelling catheter group. A tardily failure charge per unit (defined as reaccumulation of pleural fluid subsequently initial successful control) of 13% was reported compared with 21% for the doxycycline pleurodesis group. There was a modest comeback in the quality of life and dyspnoea scores in both groups. The complication rate was higher (fourteen%) in the indwelling catheter grouping and included local cellulitis (most common) and, rarely, tumour seeding of the catheter tract.

The largest series to date reported on 250 patients, with at least partial symptom control achieved in 88.viii%. Spontaneous pleurodesis occurred in 42.9% while catheters remained until death in 45.8%.148 A more than recent series of 231 patients treated with an indwelling catheter to drain pleural effusion reported a removal charge per unit of 58% afterward spontaneous cessation of drainage, with only iii.8% reaccumulation and ii.2% infection.147 This grouping included those with trapped lung (12.5% of all patients) or who had failed other therapy. A further series of 48 patients reported a spontaneous pleurodesis rate of 48%.149 Pien et al studied a group of eleven patients in whom an indwelling catheter was placed specifically for a cancerous effusion in the presence of trapped lung; ten patients reported symptomatic improvement.144

A recent series of 45 patients reported by Janes et al described three cases of catheter tract metastasis associated with indwelling pleural catheters occurring between iii weeks and nine months after insertion. Metastases occurred in ii of xv patients with mesothelioma just in only 1 of 30 patients with other metastatic malignancy.150

An indwelling pleural catheter is therefore an effective pick for controlling recurrent malignant effusions when length of hospitalisation is to be kept to a minimum (reduced life expectancy) or where patients are known or are suspected to have trapped lung and where expertise and facilities exist for outpatient direction of these catheters. Although there is a significant cost associated with the dispensable vacuum drainage bottles that connect to indwelling pleural catheters, there may be a cost reduction associated with reduced length of hospital stay or avoidance of infirmary admission.

Pleurectomy

Pleurectomy has been described as a treatment for malignant pleural effusions. Open pleurectomy is an invasive procedure with meaning morbidity. Complications may include empyema, bleeding and cardiorespiratory failure (operative mortality rates of 10–19% have been described).151–153 Pleurectomy performed by video-assisted thoracic surgery has been described in a small series of patients with mesothelioma. There is not sufficient bear witness to recommend this equally an alternative to pleurodesis or indwelling pleural catheter in recurrent effusions or trapped lung.154

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