Adult Chest Surgery

Chapter 100. Nonoperative Treatment of Malignant Pleural Effusions 

Malignant pleural effusions (MPEs) cause considerable morbidity for patients afflicted with cancer. Metastatic breast, lung, and ovarian cancers account for the majority of cases. An estimated 150,000 new patients are diagnosed annually with dyspnea secondary to MPE.1,2 Both diagnostic and therapeutic goals can be achieved with thoracentesis. Initial malignant diagnosis can be established in 50–60% of patients by means of thoracentesis.1,2 However, in almost all cases, the malignant effusions recur, and patients require long-term palliation. The ideal therapy permits expedient, low-cost management of the pleural effusion with minimal morbidity because many of these patients have terminal disease. Operative management includes drainage through the use of video-assisted thoracic surgery (VATS) techniques combined with sclerosis, as well as operative placement of indwelling drainage catheters.2–4 The operative techniques are described in Chapter 101. Nonoperative management of MPEs, the focus of this chapter, includes systemic chemotherapy and several methods of mechanical drainage, which may be combined with pleural sclerosing agents.

PATHOPHYSIOLOGY

Lung cancer is the leading cause of MPE and accounts for as many as 40% of cases, followed by metastatic breast (25%), ovarian (5%), and gastric cancers (5%). Another 10% of patients have lymphoma-induced effusions, leaving 10% without identifiable primary malignancy.2,5 Metastatic pleural spread is a complex mechanism that requires a series of mutational events leading to the sequential expression and coordination of numerous growth factors and cell surface adhesion molecules.6

Pleural seeding either by direct tumor extension or by hematogenous or lymphangitic spread initiates a series of pathophysiologic events that cause the development of effusions. These mechanisms include (1) the production of angiogenic growth factors that cause increased vascular permeability, including vascular endothelial growth factor, among others, (2) lymphatic obstruction, which perturbs the normal absorption cycle of 2–3 L of pleural fluid daily, (3) direct production of fluid by the tumor, which often occurs with ovarian malignancies, and rarely, (4) tumor invasion and blockage of venous structures, which results in venous hypertension and the ensuing alternating Starling's forces that culminate in the effusion.2

All or some of these mechanisms contribute to the effusion, which then causes dyspnea, the principal and most disturbing symptom. The dyspnea tends to be progressive, if untreated, and eventually leads to symptoms at rest, underscoring the need for palliative treatment. The severity or degree of symptoms is related to the underlying cardiopulmonary function, the size of the effusion, or the rate of accumulation. Large effusions compress the lung and alter chest wall compliance, which together cause shortness of breath not only by altering the breathing mechanics, that is, decreasing the forced expiratory volume in 1 second (FEV1) and tidal volume, but also by stimulating neurologic reflexes that lead to a subjective and uncomfortable sense of shortness of breath.2

The development of MPE portends a dismal prognosis because it is a sign of advanced disease. After diagnosis, patients with MPE experience a median survival of only 4–6 months. Only 10–15% of patients survive beyond a year. Patients with lung and gastrointestinal malignancies have a worse survival rate than those who have breast or hematologic malignancies.2

THERAPEUTIC OPTIONS

The treatment of MPE remains an important and at times difficult therapeutic challenge. The primary goal of therapy is to treat patients palliatively by relieving their dyspnea. Careful consideration of multiple factors should determine the optimal therapy. These include performance status, extent of disease, patient comfort and desires, and anatomic factors such as the degree of lung entrapment.

Systemic Therapy

CHEMOTHERAPY AND RADIATION THERAPY

Small pleural effusions usually can be treated by malignancy-specific chemotherapy and localized radiation therapy to the primary lung lesion when the effusion is negative for malignancy, especially for those with small cell lung and breast carcinomas.However, neither of these treatments is effective for moderate to large effusions, and treatment should proceed to local therapies based on symptomatic management. For a detailed discussion of chemotherapy and radiation therapy for lung cancer, see Chapters 74 and 76.

Local Therapy

THORACENTESIS

All patients with pleural effusions should undergo thoracentesis, if not for the initial diagnosis, then to determine the contribution of the effusion to the patient's dyspneic symptoms. Radiologic assessment with chest x-ray or chest CT scan after thoracentesis can be helpful in determining the extent of the disease and the degree of lung entrapment. If symptoms improve after therapeutic thoracentesis, one is afforded additional time to contemplate a more permanent solution. Failure of symptom improvement should lead to a prompt search for alternative etiologies, such as pulmonary embolus, lymphangitic carcinomatosis, or trapped lung.2,7

Thoracentesis is performed by catheter-directed aspiration of the pleural space. Large effusions usually do not need image guidance. However, ultrasound-guided catheter aspiration is useful for small to moderate pleural effusions to prevent complications such as pneumothorax or hemothorax, as well as to optimize fluid removal. Several commercial kits are available. The procedure entails the use of a commercial catheter-over-needle system. The catheter is placed through the skin, over a rib (to avoid the intercostal neurovascular bundle), and into the chest (Fig. 100-1). Placement is confirmed by fluid aspiration. Fluid is aspirated manually with a syringe or drawn into a vacuum suction container. Local anesthesia of the chest wall and parietal pleura usually is adequate for pain control in the awake patient.

Figure 100-1.

 

The thoracentesis catheter is placed using a catheter-over-needle system. The catheter is placed through the skin, over a rib (to avoid the intercostal neurovascular bundle), and into the chest.

Complications of these procedures include, as mentioned, pneumothorax from lung puncture or hemothorax from either intercostal vessel injury or injury to other intrathoracic vascular structures, liver, or splenic puncture, which is notably rare. Other complications include reexpansion pulmonary edema, which can occur after large-volume thoracentesis. The exact volume of pleural fluid one can withdraw without developing this condition is unknown, but 2 L is typically the limit for patients with trapped lung or a fixed mediastinum, in whom the pleural pressure increases more dramatically with suction.2,7 The precise mechanism is unknown, and supportive measures with supplemental oxygen and occasionally diuretics usually will suffice. At times, especially in the elderly or medically compromised patient, the pulmonary edema is so severe that intubation and ventilatory management are required for several days.8

Patients with recurrent effusions after thoracentesis can be managed in several ways. Repeat thoracentesis is an option for patients with extremely poor life expectancy (<1–2 months) who are either unwilling to undergo further intervention or for whom the anticipated need for fluid removal does not exceed two or three additional treatments. For patients whose symptoms improve with initial thoracentesis, the treatment decision turns on whether the lung expanded after thoracentesis or remained trapped. If the lung expanded fully, the patient may undergo pleurodesis with a chemical sclerosant such as talc, doxycycline, or bleomycin, among many other agents.This option is valid for patients who are medically fit enough to tolerate the inflammatory response that ensues after pleural installation, especially with talc. Talc pleurodesis has been associated with acute respiratory distress syndrome and death and hence must be used with extreme caution in the elderly or medically compromised patient with poor cardiac and pulmonary function.Patients with trapped lung resulting from a long-standing or fibropurulent effusion with fibrin peel formation on the lung surface are not candidates for pleurodesis. Pleural apposition is not possible in this setting, and therefore, the pleural space cannot be obliterated with sclerosing agents. These patients should be managed with a long-term indwelling pleural catheter and possibly decortication if the malignancy is of sufficiently low grade and expected survival sufficiently long to warrant this approach. The treatment algorithm in Table 100-1 was created with the foregoing principles in mind.

Table 100-1. Treatment Algorithm for Pleural Effusion

 
 

For patients with lung reexpansion after thoracentesis, viable options include (1) operative intervention with VATS drainage of the effusion followed by pleurodesis, typically with talc, (2) chest tube placement followed by pleurodesis, and (3) indwelling pleural catheter placement followed by pleurodesis. If the patient has poor pulmonary function and is medically compromised, placement of an indwelling catheter may be the only option.

CHEST TUBE PLACEMENT

One of the most basic procedures in thoracic surgery is the placement of a chest tube. Chest tube insertion is an art unto itself. The basic steps for chest tube insertion are summarized in Table 100-2. Briefly, the ideal placement for chest tube insertion varies (especially if there has been previous chest surgery), but for most patients, the anterior or midaxillary line in the fifth or sixth interspace is appropriate. This corresponds to the nipple line in males and just under the breast in females (Fig. 100-2). The precise location is determined by marking the scapular tip, costal margin, and anterior iliac spine. Using these discrete points as a guide, the incision is marked with a felt tip pen and should be at least 3–4 cm in length (Fig. 100-3). The chest tube is inserted over the rib to avoid injury to the neurovascular bundle (inset). The tube is left in place for several days until the drainage subsides to 200 mL/d or less. The success rate of chest tube drainage alone is lower compared with chest tube and chemical pleurodesis combined and varies from 10% to 60% depending on the series examined.2,7Therefore, if chest tube drainage is performed, pleurodesis is recommended once the lung has fully expanded because efficacy rates of 80–90% can be achieved.2

Table 100-2. Chest Tube Insertion

 

1.     Confirm the side of effusion (right versus left) clinically and radiologically. Obtain necessary material [i.e., chest tube, chest tube suction unit (e.g., Pleur-evac), chest tube tray, including scalpel blade and handle, Kelly clamps, etc.).

2.     Review the chest x-ray or chest CT scan to determine ideal placement of the tube.

3.     Position the patient. For most chest tube insertions, the patient should be placed in the lateral decubitus position with the arms secured.

4.     The ideal placement for chest tube insertion in most patients is the anterior or midaxillary line in the fifth or sixth interspace, which corresponds to the nipple line in males and just under the breast in females (see Fig. 100-2).

5.     Mark the scapular tip, costal margin, and anterior iliac spine with a felt tip pen. Mark the incision to be made (at least 3-4 cm) (see Fig. 100-3).

6.     Give appropriate analgesia with IV conscious sedation, if needed, and generous local anesthesia with 1% lidocaine not only in the skin but also into the subcutaneous tissue and tissues just above the pleura.

7.     Make the skin incision with a knife, and dissect bluntly or with a knife to a level above the rib.

8.     Enter the pleura above the rib by using a blunt Kelly clamp with careful control of its tip. Feel the chest to ensure absence of adhesions.

9.     Place a chest tube (28F right-angle chest tube to base for fluid), and guide to the appropriate position.

10.  Secure the chest tube and obtain a chest x-ray.

 

 

Figure 100-2.

 

The usual position for chest tube placement is below the nipple line in males and below the breast in females.

 

Figure 100-3.

 

Determining the incision site for chest tube insertion.

PIGTAIL CATHETER INSERTION

The technique for catheter-directed drainage is similar to thoracentesis (Fig. 100-4). An 8–10F pigtail catheter is placed and left in the pleural space. The catheter is placed using a Seldinger catheter-over-wire technique after fluid has been aspirated with a needle and syringe. The catheter is placed to suction drainage until the pleural space has been evacuated.2,4 Drainage with a pigtail catheter has many advantages over chest tube placement, including ease of placement (because it requires only a stab incision), improved patient comfort owing to its small size, and portability, which permits easy home or hospice care. The risks of placement are similar to those of thoracentesis, with pneumothorax with bleeding being the foremost complication. Pneumothorax in this scenario can be treated by suction evacuation of the space after placement. The major disadvantage in this approach is that catheters often become clogged with fibrin debris and hence prevent complete evacuation of the pleural fluid. In patients with full lung reexpansion, pleurodesis can be achieved by instillation of chemical sclerosants through the catheter. Recent studies have demonstrated the utility of this technique, with efficacy rates similar to those of chest tube drainage and chemical pleurodesis but lower associated cost because it can be performed in an ambulatory setting.

Figure 100-4.

 

Pigtail catheter placement.

CHRONIC INDWELLING CATHETER SYSTEMS

Chronic indwelling pleural catheters such as the PleurX system (15.5F) (PleurX Pleural Catheter and drainage systems, Denver Biomedical, Inc., Golden, CO) also have been used to treat chronic pleural effusions. Indwelling catheter placement is similar to pigtail catheter placement and is achieved by means of Seldinger technique,1,9 although an open technique similar to chest tube placement works as well (Fig. 100-5). The catheter is placed under local anesthesia. These systems, much like pigtail catheters, can be placed in an ambulatory setting. The chief benefits are patient comfort and ease of placement. Because of their large size, indwelling catheters rarely occlude. They are manufactured with a cuff at the skin exit site, which permits tissue incorporation and serves as a barrier to infection. The risks of indwelling catheter placement are similar to those noted for chest tube and pigtail catheter placement. The risk of infection increases with long-term use.1,9 These catheters have been demonstrated to be safe and effective in relieving symptoms and may be more cost-effective than chest tube pleurodesis. Like chest tubes and pigtail catheters, they can be used to instill sclerosants for pleurodesis.1,2,9 Current practice recommends placement in patients with trapped lungs or in individuals who otherwise would not tolerate pleurodesis.

Figure 100-5.

 

PleurX pleural catheter system.

PLEURODESIS

Chemical pleurodesis serves as an adjunct to mechanical pleural drainage. It should be performed in patients with malignant effusions who have a high likelihood of recurrent effusion after drainage. Pleurodesis is indicated for patients who experience full lung reexpansion after mechanical treatment, which makes pleural apposition possible. Various sclerosing agents are capable of inciting the inflammatory response needed to cause fusion of the visceral and parietal pleurae, thereby obliterating the pleural space and preventing fluid accumulation. Several agents have been used, including talc; antibiotics such as doxycycline and tetracycline; chemotherapy agents such as bleomycin and mitomycin C, and even autologous blood or bacteria such as Corynebacterium parvum, although the latter is no longer available.Success rates vary for each, but talc is generally regarded as the best agent, with success rates (defined as reaccumulation of pleural fluid within 90 days) of 80–95% in most series. As mentioned previously, talc pleurodesis is not without risk because it can cause acute respiratory distress syndrome and death in patients with medical or pulmonary impairment and thus should be used with extreme caution in this group. Our recommendation is to follow the general policy of limiting talc instillation to 2 g for pleurodesis in medically compromised patients and to never exceed 4 g of talc in any patient, irrespective of medical fitness.2

Pleurodesis is performed by instilling the sclerosing agent through the pleural drain (i.e., chest tube, pigtail catheter, or indwelling catheter) using a local anesthetic (e.g., lidocaine or benzocaine) because the ensuing inflammatory response is quite painful. Instillation times, varying from as few as 30 minutes to as many as 4 hours, have been reported with little improvement in efficacy after 1–2 hours. Our policy is to administer the sclerosing agent for 1 hour while the patient moves through various positions to ensure even distribution of the slurry. However, these maneuvers are more for comfort than for necessity because spontaneous respiration should disperse the sclerosant evenly. Fever and pain are common and treated accordingly. Pronounced inflammatory reactions are rare and should be monitored during talc instillation, as discussed earlier. For this reason, we avoid performing bilateral pleurodeses in the same setting, preferring to schedule the patient for a second procedure at a later time. After instillation, the pleural drains are placed to suction for 48–72 hours. The pleural drain should be removed when pleural drainage is between 200 and 300 mL/day.

FUTURE THERAPIES

Future therapies for recurrent pleural effusion are aimed at treating the mechanisms that underlie malignant effusion formation. Specifically, numerous trials are attempting to determine the efficacy of antiangiogenic therapy. Current phase I and phase II trials are also examining the efficacy of anti-vascular endothelial growth factor therapy.Efficacy will be determined after adequate trials, but assuredly these therapies will come at an economic price.

SUMMARY

The overriding goal of managing patients with MPE is to treat the dyspnea. In this regard, it is important to select the most cost-effective, low-morbidity regimen available in line with the patient's clinical circumstances. For patients undergoing nonoperative therapies, drainage followed by pleurodesis is the preferred therapy when the lung reexpands after pleural drainage and if the patient is healthy enough to tolerate the inflammatory consequences of pleurodesis. The method used (i.e., chest tube, pigtail catheter, or VATS) is highly dependent on surgeon and institutional preference. For patients unable to tolerate pleurodesis or with persistent lung entrapment after pleural drainage, a chronic indwelling catheter system (e.g., PleurX) may be the best option. The treatment scheme must take into account not only patient comfort but also patient preference in this group of often terminally ill patients.

CASE HISTORY

A 76-year-old woman with stage IV non-small cell lung cancer was referred by her oncologist for surgical evaluation and treatment of dyspnea. The patient had undergone four cycles of cisplatin-based chemotherapy but continued to have a left pleural effusion, which had increased in size over the last 2 months. She presented with a progressive dyspnea that had worsened significantly over the past 2 weeks. She brought a chest film with her to the appointment (Fig. 100-6) showing clear evidence of a left pleural effusion.

Figure 100-6.

 

Chest x-ray showing evidence of left pleural effusion in a patient with stage IV non-small cell lung cancer who presented for treatment of dyspnea.

The immediate options included VATS pleurodesis, radiation therapy, ambulatory PleurX catheter placement, and thoracentesis. A decision was made to proceed with thoracentesis both to evaluate the extent to which the effusion contributed to the patient's symptoms and to determine the degree of lung expansion after the effusion had been evacuated. Two liters of fluid was evacuated from the left chest after thoracentesis, and the patient's symptoms improved substantially. On follow-up chest x-ray, there was a large basilar space, indicating incomplete lung reexpansion. The options were placement of a chronic indwelling catheter, intrapleural administration of mitomycin, VATS decortication with talc pleurodesis, and chest tube placement with talc pleurodesis. However, since the left lung did not fully expand in this terminal patient, a chronic indwelling catheter (e.g., PleurX) was recommended.

EDITOR'S COMMENT

Patients with malignant pleural effusions represent one of the most tenuous groups of patients. Their limited survival and poor performance status requires careful consideration of the balance between the benefits of palliation and the morbidity associated with the procedure offered.

–LZ

REFERENCES

1. Putnam JB Jr, Walsh GL, Swisher SG, et al: Outpatient management of malignant pleural effusion by a chronic indwelling pleural catheter. Ann Thorac Surg 69:369–75, 2000. [PubMed: 10735665]

2. Putnam JB Jr: Malignant pleural effusions. Surg Clin North Am 82:867–83, 2002. [PubMed: 12472134]

3. Pollak JS: Malignant pleural effusions: Treatment with tunneled long-term drainage catheters. Curr Opin Pulm Med 8:302–7, 2002. [PubMed: 12055393]

4. Hingorani AD, Bloomberg TJ: Ultrasound-guided pigtail catheter drainage of malignant pericardial effusions. Clin Radiol 50:15–9, 1995. [PubMed: 7834968]

5. Rodriguez-Panadero F, Borderas Naranjo F, Lopez Mejias J: Pleural metastatic tumours and effusions: Frequency and pathogenic mechanisms in a post-mortem series. Eur Respir J 2:366–9, 1989. [PubMed: 2786818]

6. Grove CS, Lee YC: Vascular endothelial growth factor: The key mediator in pleural effusion formation. Curr Opin Pulm Med 8:294–301, 2002. [PubMed: 12055392]

7. Tan C, Sedrakyan A, Browne J, et al: The evidence on the effectiveness of management for malignant pleural effusion: A systematic review. Eur J Cardiothorac Surg 29:829–38, 2006. [PubMed: 16626967]

8. Massad I, Halawa SA, Badran I, Al-Barzangi B: Negative pressure pulmonary edema: Five case reports. Middle East J Anesthesiol 18:977–84, 2006. [PubMed: 17094538]

9. Putnam JB Jr, Light RW, Rodriguez RM, et al: A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions. Cancer 86:1992–9, 1999. [PubMed: 10570423]



If you find an error or have any questions, please email us at admin@doctorlib.info. Thank you!