Bronchopleural Fistula

#### **Chapter 5**

## Bronchopleural Fistula after Pulmonary Resection: Risk Factors, Diagnoses and Management

*Kristina Jacobsen*

### **Abstract**

Bronchopleural fistula (BPF) after a pulmonary resection is rare with some of the most life-threatening consequences and a high mortality rate. Contamination of the pleural space resulting in empyema and spillage of the infected fluid into the remaining lung leading to respiratory distress remain the biggest concerns with BPF postoperatively. There are many patient characteristics and risk factors that can be evaluated to decrease the chance of a postoperative BPF. Presentation of BPF can be early or late with the late BPF more difficult to diagnosis and manage. Many options to treat BPF include surgical repair, conservative management, and endoscopic treatment.

**Keywords:** bronchopleural fistula, pneumonectomy, empyema, lung cancer, thoracic surgery

#### **1. Introduction**

Bronchopleural fistula (BPF) is defined as a central fistulous connection of inspired air between trachea, major, lobar, or segmental bronchus into the pleural space [1, 2]. Or a BPF can occur peripherally when there are connections between the distal segmental bronchus or lung parenchyma and the pleural space [1, 2]. Although rare, managing a BPF is challenging and represents a high morbidity and mortality.

#### **2. Etiology**

After an anatomical lung resection, a BPF is rare but severe complications can occur and may be fatal. The BPF incidence after a pneumonectomy for lung cancer is between 4.5% and 20% and 0.5–1% after a lobectomy [1, 3, 4]. The mortality rate after a pneumonectomy is estimated to be 18–71% with a much lower rate for lobectomy [2, 4]. The pleural space is exposed to the endobronchial bacterial flora with the pleural effusion leaking into the major airway and into the peripheral alveolar space. The main cause of death is aspiration pneumonia, empyema, and subsequent respiratory distress [4, 5]. Treatment for BPF after surgery requires emergency

treatment due to patient's lung volume loss and short-term poor respiratory function with surgical damage to the respiratory muscles [5].

The less common causes of BPF include suppurative lung processes such as septic pulmonary emboli, infected pulmonary infarctions, or tuberculosis [6]. Neoplasms with tumor invasion into the pleural space may also lead to BPF. Iatrogenic etiologies due to complications with chest tube insertion, thoracentesis or lung biopsies may result in BPF [6].

When considering different surgical approaches and incidence of BPF, one study evaluated the Society of Thoracic Surgeons and General Thoracic Surgery Database (STS-GTD) to compare outcomes of video-assisted thoracoscopic surgery (VATS) and robotic-assisted lobectomy (RATS) for primary clinical stage I or II non-small cell lung cancer (NSCLC) at high volume centers from 2009 to 2013. This study identified 1,220 RATS and 12,378 VATS patients. The incidence of BPF between these two groups was not statistically significant (0.6% vs. 0.3%, p = 0.08) [7]. Another study that included 737 cases of VATS lobectomies and 748 cases of open lobectomies for the surgical treatment of resectable non-small cell lung cancer showed no statistical difference in incidence of BPF postoperatively [8].

#### **3. Risk factors**

Certain anatomic, technical, and patient factors lead to increased risk for BPF (**Table 1**). Generally, right-sided pneumonectomy is associated with high risk of BPF. Devascularization of the bronchial stump, diabetes, malnutrition, steroids, neoadjuvant chemoradiotherapy, stump closure, residual carcinomatous tissue, presence of empyema and postoperative mechanical ventilation all lead to increased risk of bronchial stump dehiscence [9, 10].

#### **3.1 Right sided surgery and right pneumonectomy**

Generally, right-side pneumonectomy and right lower lobectomy are associated with high risk of BPF and are multifactorial. The right upper pulmonary artery is made up of the apical, anterior, and posterior ascending branches [11]. The apical and anterior branches are located in the front of the hilum and the posterior is located at the posterior segment of the horizontal fissure [11]. The right lower pulmonary artery is divided into the dorsal and basilar segment and is located at the corresponding position of the posterior ascending branch in


#### **Table 1.** *Risk factors for bronchopleural fistula after pulmonary resection.*

#### *Bronchopleural Fistula after Pulmonary Resection: Risk Factors, Diagnoses and Management DOI: http://dx.doi.org/10.5772/intechopen.100209*

the horizontal fissure [11]. This single bronchial artery supplies the entire right mainstem bronchus whereas the left mainstem bronchus has a vascular supply by two bronchial arteries [9]. During lymphadenectomy if the single artery of the right bronchus is damaged, the bronchial stump becomes ischemic [4].

After a right pneumonectomy, the risk for BPF increases due to the diversion of the entire cardiac output going through the smaller left lung and increased load on the right ventricle [12]. This compensation results in decreasing circulating blood volume, pulmonary hypertension, increased pulmonary pressures, increased pulmonary vascular resistance and right ventricular failure [12, 13]. Loss of the larger right lung may compromise pulmonary function resulting in respiratory failure predisposing the patient to the postpneumonectomy edema syndrome [12, 14, 15]. Larger perioperative fluid resuscitation causes overload of the pulmonary circulation and right ventricle and has been reported to be a poor outcome predictor [14, 15].

Anatomical differences in the right bronchus versus the left are significant factors in increased risk of BPF. The right main bronchus is more vertical and wider than the left increasing the accumulation of secretions in the bronchial stump [4]. The right mainstem bronchus is not naturally buttressed by mediastinal tissue coverage and therefore likely to be exposed to the thoracic pleural free space [9, 15]. The left main bronchial stump tends to be protected and covered by the aortic arch with its surrounding vascularized mediastinal tissue [9, 15]. The left bronchial stump retracts within that tissue under the aortic arch after dissection giving protection from the pleural free space.

#### **3.2 Lymph node dissection**

The surgical approach to mediastinal lymph node dissection at the time of pulmonary resection for NSCLC has been a subject of interest for several decades. Accurate pathologic lymph node examination offers the most accurate staging and survival benefit and provides the most significant prognostic factor [16]. Accurate nodal staging increases survival by improved risk categorization, increased detection of candidates for adjuvant therapy and possibly resection of oligometastatic disease [17]. Staging NSCLC may have lymph node metastases even after appearing localized by imaging which makes the extent of mediastinal lymph node removal controversial [18]. Patients with negative nodes by systematic lymph node dissection with early stage NSCLC did not have improved survival with complete mediastinal lymph node dissection [17–19]. Intraoperative lymph node sampling is removal of one or more lymph nodes decided by preoperative or intraoperative findings and is determined by the surgeon [19]. Systematic nodal dissection contains all mediastinal tissue containing lymph nodes and is removed systematically within anatomical landmarks. To meet minimal recommendations, for right-sided cancers, mediastinal lymphadenectomy should contain stations 2R, 4R, 7, 8, and 9. Left side stations 4 L, 5, 6, 7, 8 and 9 should be included [17–19]. Patients should have N1 and N2 node resection with a minimum of N2 stations sampled [17–19]. Some argue that systematic mediastinal lymph node sampling versus mediastinal lymph node dissection is adequate for staging and that complete dissection does not provide survival advantage as most patients with N2 disease die from systemic disease [18, 19].

Lymph node dissection removes tissue from adjacent organs and skeletonization of intrathoracic structures. It includes enblock removal of tissues with cancer cells that includes lymph nodes and fatty tissue within bronchus, trachea, superior vena cava, aorta, pulmonary vessels, and pericardium [17, 20].

Healing of the bronchial stump is delayed due to decreased post-operative blood supply after lymph node dissection. Superior and inferior mediastinal lymph node

dissection for NSCLC is widely performed adjunct to pulmonary resection [21]. Vascular supply to the suture line is watershed from the descending thoracic aorta across the mediastinum and is decreased after mediastinal lymph node dissection [11]. Ischemic bronchitis after lymph node dissection due to decreased bronchial microvascularization negatively influences bronchial stump healing [11, 21]. Lymph node sampling rather than complete lymphadenectomy leading to devascularization of the bronchial stump can permit adequate blood flow to the bronchial stump [21]. Meticulous technique while dissecting around the bronchus is necessary. Preventing devascularization of the bronchus during lymph node dissection can decrease the incidence of fistulization [9, 21].

#### **3.3 Stump closure**

The Sweet principles on bronchial closure, emphasized in 1945 are still followed today. Trauma to the end of the bronchus should be minimized and the blood supply must be preserved all the way to the end cut of the bronchus [22]. The cut edges of the bronchus should be carefully approximated [22]. Tissue reinforcement of the bronchial closure should be provided. Clamps should not be used on the proximal bronchus [22]. The major change to Sweet's original description has been leaving the posterior membranous wall longer when cutting the bronchus so it can be used as a flap to decrease tension on the closure [22].

Typically, when the bronchus is pulled to place a stapler, an abrupt onset of vagal-induced atrial fibrillation or bradycardia may occur, along with hypotension that leads to releasing the bronchus [23]. There is a natural tendency with the next attempt to reduce bronchial traction allowing for a longer stump. Using a Roticulator linear stapler is useful to suture and clip the main bronchus close to the carina [23]. To avoid pooling of secretions within the bronchial stump, the stump should be resected back to its origin and for a pneumonectomy divided as close to the level of the carina as possible [9, 24]. This is critical to avoid secretions pooling resulting in infection and stump breakdown.

When closing a very proximal right bronchial stump or thickened bronchial wall, attention must be directed to ensure there is no closure under tension [25]. Closure under tension can be implicated in right sided BPFs at the point of transection of the right mainstem bronchus as it is generally larger than the left [25]. By the Law of LaPlace, the tension on the curved cartilaginous membranes and the fluid within the crenelated surface is higher in the larger orifice of the right bronchial stump [18, 26, 27]. Elimination of the stump diverticulum may reduce surgical line tension [18, 26, 27]. The cartilaginous ring at the origin of the right mainstem bronchus tends to keep the bronchus open and closure should be parallel to the bifurcation spur of the resected bronchus [21, 28]. This decreases the intraluminal deformity of the remaining bronchi with the straightened angle of the longitudinal axes [21,28].

#### *3.3.1 Suture vs. staple closure*

The surgical technique of bronchial closure remains controversial and has been studied extensively. The preferred technique of pulmonary hilum vessel ligation and bronchial stump closure has troubled thoracic surgeons for years. In 1909, regarding bronchial stump closure, Meyer advised his inversion technique [29]. In 1945, Sweet described the longitudinal, single interrupted silk suture closure [29, 30]. Dr. Mark Ravitch started using staplers in the United States in 1964 after having observed their early development in Russia [29]. In 1970, Kirksey reported 147 patients who underwent pulmonary resection with disposable and plastic

#### *Bronchopleural Fistula after Pulmonary Resection: Risk Factors, Diagnoses and Management DOI: http://dx.doi.org/10.5772/intechopen.100209*

American staplers called Thoraco-Abdominal (TA) [29]. Reluctance to use vascular staplers due to fear of fatal hemorrhage because of malfunction continued the debate concerning pulmonary hilum vessel manual ligation versus stapled division for many decades [29]. The cessation of the alarm resulted after Asamura et al., in 2002 published results of 842 vascular divisions using endoscopic staples with 0.1% incidence of stapling failure and Yano et al., in 2013 reported 3393 pulmonary vein and artery stapling uses with a failure rate of only 0.27% [29].

It is decided by the surgeon perioperatively to use either manual suturing or stapling methods [31]. None of these have proven superiority in reducing the incidence of BPF and around a 4% rate of BPF has been reported for mechanical stapling and suture technique [31, 32]. Ucvet et al., 2011 reported the weakest part of the line are the end points of the stapler and it may incompletely close the tissue [31]. The staple line that exceeded the length of the bronchus caused a detachment in this end site creating a microfistula. These microfistulas can lead to large BPF along with infections [31]. To provide stump safety, lateral suturing to the weak and risky stump end points was required [31].

Endoscopic staplers have 2 differences compared to conventional TA type staplers: proximal and distal ends can be closed, both division and stapling can be performed simultaneously in one firing motion [31, 33]. The advantages of using endostaplers during a pulmonary resection are: (1) Time required for closure can be reduced, compared to the TA stapler when closure of the distal end of the bronchus and division are required; (2) Both proximal and distal ends of the bronchi are simultaneously and tightly closed without purulent or contaminated discharge which minimizes contamination of the operative field; (3) By selecting the appropriate cartridges, endostaplers can be used safely in vascular division [31, 33].

Suture closure is considered when the bronchial wall is hardened due to calcification [10, 21, 33]. Suture closure is also used with position difficulty due to hilar adenopathy or when the tumor is close to the pulmonary hilum due to a more extensive proximal dissection or a technically difficult bronchial stump [10, 21, 33]. Manual suturing may have the advantage of allowing inspection and assessment of the bronchial mucosa quality. Tumor fragments may also be recovered after the main bronchus is clamped [34].

#### **3.4 Tissue coverage of the bronchial stump**

Generally, wound healing has three phases: (1) inflammatory phase (2) proliferation phase (3) remodeling phase [35]. The inflammatory phase is marked by the aggregation of platelets, infiltration with leukocytes and coagulation. This phase begins soon after injury and is followed by the proliferation phase. The proliferation phase is characterized by reepithelialization, fibroplasia, angiogenesis, and wound contraction. Persistent inflammation can last about 2 weeks and likely causes robust adhesion. The remodeling phase takes place over months when the epithelium produces collagen and matrix proteins responding to the injury [35]. The phase of wound healing needs to be considered when deciding which type of bronchial closure is used.

Several options are available for coverage of bronchial closure. To reduce the incidence of postpneumonectomy BPF with soft tissue buttressing after bronchial closure has been debated. Many suggest stump reinforcement in patients with increased risk factors for BPF [36]. Cerfolio et al., 2005 suggests the best way to treat postoperative complications is to prevent it [37]. Local soft tissue coverage may provide vascular ingrowth to promote stump healing and effectively contain a small bronchial stump dehiscence [38]. Algar et al. 2001, found that the absence of bronchial stump tissue coverage was an independent predictor of BPF in the final multivariable model (p = 0.039) [32].

#### *3.4.1 Intercostal muscle flap*

The intercostal muscle flap causes no functional disability, is easy to harvest, has adequate length to reach most sites, has adequate vascularity and is harvested through the same thoracotomy incision [39]. Sfyridis et al., discovered the group that received an intercostal muscle flap had a lower incidence of development of BPF (0% versus 8.8%; *p* < 0.02) [40]. This flap is harvested prior to chest retraction to not crush the flap and cause damage to the blood supply. The use of cautery to harvest this flap is necessary because it is lacking periosteum and over time will not calcify [9, 37, 40]. The intercostal muscle flap is harvesting by cutting approximately two-thirds of the posterior aspect of the latissimus dorsi and the entire serratus anterior muscle is spared [37]. The rib is not shingled or cut. For harvesting, rib instruments are not used. The intercostal muscle flap, usually overlying the sixth rib is harvested using cautery prior to chest retraction from the under surface of the fifth rib. Starting at the distal end of the muscle under the serratus anterior muscle, cautery is lowered from 40 to 70 and carefully the muscle is dissected with both hot and cold cautery. So the intercostal vein is not injured, the cautery tip is positioned so it is almost parallel with the surface of the fifth rib. The intercostal is posteriorly freed from the sixth rib, past the lumbar-dorsal fascia but not freed from the undersurface of the fifth rib past this structure due to risk of injury to the vein posterior of the fifth rib with any further dissection. The bronchial stump is then tested [37].

#### *3.4.2 Pericardial fat pad*

In a retrospective study, Taghavi et al., found 93 patients who underwent pneumonectomy for primary lung cancer, identified no BPF during follow up after using a pedicled pericardial flap for bronchial stump coverage [41]. A pericardial fat pad is harvested from the anterolateral pericardium, pedicled at its cranial part, avoiding inclusion or injury to the phrenic nerve [9, 42]. A wide based pedicle should be used to assure vascularity of the flap. Careful attention should be used to avoid twisting the pedicle. The flap is attached caplike over the bronchial stump with numerous single mattress stitches to avoid devascularization when tied down over the four corners of the bronchial stump. The defect in the pericardium is then reconstructed with mesh [9, 42].

#### *3.4.3 Serratus anterior flap*

Bronchopleural fistula is exceedingly rare when a pedicled muscle flap is used to buttress the lobar bronchus, even after preoperative radiation doses of 60Gy or higher are administered [43]. To provide sufficient protection after preoperative radiation, using omental or serratus as a prophylactic buttress for the highly irradiated right main stem bronchus after a right pneumonectomy is recommended [43].

If the patient is believed to be at extraordinary risk of stump complications, larger muscle or omental flaps are used. The serratus anterior flap and omental flap are also used to treat a postoperative bronchopleural fistula to close the fistula [43, 44].

The serratus anterior muscle, one of the workhorse flaps is easily harvested, reliable, often preserved during the initial pneumonectomy due to its utility in dealing with potential complications [44]. The vascular pedicle that runs on the lateral undersurface of the scapula is where the serratus anterior muscle is based [25]. This muscle is mobilized and placed between the ribs in the second or third interspace where it will reach the hilum without tension. The thoracodorsal vascular pedicle is protected throughout the dissection [44]. With tight interspaces, compromising the

#### *Bronchopleural Fistula after Pulmonary Resection: Risk Factors, Diagnoses and Management DOI: http://dx.doi.org/10.5772/intechopen.100209*

vascular supply of the flap, a segment of the third rib can be removed to allow the flap to enter the pleural space easily [25]. The serratus anterior flap is secured with interrupted absorbable sutures to the mediastinal areolar or peribronchial tissue [25] (**Figure 1**). This tissue helps with infection control and healing due to its blood supply emanating from regions beyond the inflamed field [25]. The flap is placed over the bronchial stump with uninterrupted suture to secure the closure [9, 25, 44].

#### *3.4.4 Omental flap*

The omentum has superior blood supply and plasticity which allows for a very safe and easy bronchus closure even in the presence of fibrotic tissue or infection [45]. The omentum with a rich blood supply assures adequate antibiotic and oxygen delivery [46]. Delivering potent angiogenic factors, the omentum improves neovascularization of the bronchial suture lines in experimental models. Omental transposition does not impair muscle function or produce chest wall deformities seen with major muscle flaps [46].

The disadvantage of tradition omental flap transposition extends the surgical procedure into the abdomen, requiring laparotomic access. Usually the omentum is mobilized through the upper midline abdominal incision, transposed into the chest via a substernal or anterior transdiaphragmatic route [46]. This description applies a transdiaphragmatic harvesting technique of the greater omentum performed through the standard thoracotomy [46].

The five centimeter incision in the diaphragm is performed radially between its anterior insertion and central tendon through the standard thoracotomy [46, 47]. Oval forceps are used to slide through the diaphragm into the abdominal cavity. Once confirmation the omentum is free of adhesions, the greater omentum gently can be retracted through the diaphragm into the chest. The omental insertion of the transverse colon is identified and divided as extensively as possible. The most distal omental extremity is identified in the chest cavity by gentle traction and subsequently isolated carefully inspecting its vascular supply. After confirming the omental flap has no traction on the stomach or colon, the omentum is sutured to the bronchial stump in the usual fashion. The diaphragmatic incision is closed leaving a large enough opening to avoid strangulation of the omentum. The omental flap is sutured with interrupted sutures to the diaphragmatic opening to further relieve

#### **Figure 1.**

*The serratus anterior muscle is harvested and mobilized into the chest between the ribs in the second or third interspace with rib segmentation. (Sugarbaker D, Bueno R, Burt B, et al, editors. Adult chest surgery. 3rd edition. New York: McGraw-Hill Education; 2020; with permission).*

any tension. This technique is appropriate to reinforce the bronchial stump and can be large enough to fill the pleural space [46, 47].

#### **3.5 Residual carcinoma at bronchial margin**

Residual disease is characterized by residual carcinomatous tissue within the margin of resection either under visible inspection or under microscopy [48]. Residual disease at the bronchial stump may cause poor prognosis with the increased risk of lung cancer recurrence both distantly and locally [48]. It may also decrease the bronchial stump anastomosis which can lead to a fatal bronchopleural fistula or empyema [48, 49]. In all pulmonary resections, the estimated incidence of residual disease left at the bronchial stump is 4–5% [49]. Asamura et al. reported in 2359 patients that the most important risk factor for a BPF was resection type, followed by presence of residual microscopic tumor at the resection margin (p < 0.01) [28]. Survival is worse in patients with bronchial margin residual disease; 1 and 5 year survivals range between 20 and 50% and 0–20% respectively [48]. Mediastinal lymph node involvement is associated with the poor survival in 75–85% of patients with residual bronchial margin disease [48]. Radiotherapy or reoperation may be considered in these patients [48, 49].

#### **3.6 Neoadjuvant chemoradiotherapy**

Neoadjuvant chemoradiotherapy is a crucial strategy in multidisciplinary treatments to improve the survival rate and resectability for patients with lung cancer [50]. Especially for patients with advanced lung cancer, chemoradiotherapy can eliminate or reduce the micro-metastasis. Previously published randomized control trials have been integrated with recent systematic reviews and have concluded that neoadjuvant chemoradiotherapy can significantly benefit the survival outcomes in operable patients [50]. Relative to other pulmonary resections, pneumonectomy has been associated with increased morbidity and mortality. The mortality for a pneumonectomy after neoadjuvant therapy has reports with very low mortality (<5%) countered by other reports with alarmingly high mortality (>20%) [51]. For the patient with N2 disease who requires a pneumonectomy, the correct approach can be unclear with the postoperative and intraoperative complications remaining a debate [50, 51]. Bronchial mucosa ischemia is induced by radiotherapy but the mucosal blood flow can recover in eight to ten days after completion of therapy. Early effects of radiation can cause mucosal edema and inhibit capillary angiogenesis [52]. Late effects of radiation cause fibrotic small vessel disease through radiation vasculopathy [52]. Radiation pneumonitis, poor wound healing, and fibrosis can occur in previously irradiated bronchial tissue with a higher perioperative and postoperative complication leading to a bronchopleural fistula [53, 54]. Induction therapy may cause injury to the bronchial microvascularization predisposing to airway complications but published literature does not support the notion that all pneumonectomies after therapy are associated with postoperative mortalities [51, 55].

#### **3.7 Empyema**

Empyema is the presence of purulent fluid in the postpneumonectomy pleural space. Postpneumonectomy empyema occurs in 2–16% of patients and can be life threatening [55]. This postoperative complication is associated with BPF which can further increase morbidity and mortality [56]. Most BPFs associated with empyema is monomicribial with most pathogens being Streptococcus or

*Bronchopleural Fistula after Pulmonary Resection: Risk Factors, Diagnoses and Management DOI: http://dx.doi.org/10.5772/intechopen.100209*

Staphylococcus species and occur within 10 to 14 days of surgery [52, 57]. A late empyema can occur more than three months to 40 years after a pneumonectomy and is most often acquired via a hematogenous route [52, 57]. After a pneumonectomy, to avoid spillage of infected fluid into contralateral lung the patient should be kept upright at least 45 degrees [52]. An early empyema withing 10 to 14 days after surgery presents with expectoration of purulent sputum and fever [57]. Radiographic findings show a shift of the mediastinum away from the postpneumonectomy space, development of a new or sudden change in the existing air-fluid level, and failure of the mediastinum to shift normally in the immediate postoperative period [57]. Empyema diagnosis is confirmed by fluid sample in the postpneumonectomy space [57].

#### **3.8 Mechanical ventilation**

Mechanical ventilation in patients after a pneumonectomy, subjects the bronchial stump line to increased wall tension and continuous barotrauma [1]. Positive pressure ventilation can be challenging in these patients and the aim is to prevent further lung injury by keeping the airway pressure below the critical opening pressure of the fistula, optimizing pleural suction pressures and provide adequate alveolar ventilation of sufficient gas exchange [58, 59]. To decrease the flow across a BPF, reducing the proportion of minute ventilation provided by the ventilator, minimal levels of positive end expiratory pressure (PEEP), low tidal volumes and respiratory rate are helpful [1, 59]. Adverse effects in mechanically ventilated patients with BPF include loss of effective tidal volume, incomplete lung expansion, inability to remove carbon dioxide and prolonged ventilatory support [59]. The majority of reported studies report a significant relationship between the occurrence of BFP and mechanical ventilation after pneumonectomy [60].

#### **3.9 Diabetes, chronic steroid use, nutritional status**

Typically, surgeons consider diabetes mellitus in patients requiring surgical intervention an important contributor to some fatal adverse events [61]. Diabetic microangiopathy alters the vascular bed causing small vessel ischemia impairing proper wound healing [40]. This decreases the oxygen diffusion capacity and the bronchial stump circulation is particularly prone to poor wound healing [52, 61]. The largest retrospective analysis reported by Asamura et al. in 1992, showed statistical results from both univariate and multivariate analysis indicating significantly increased risk of postoperative BPF in patients with diabetes [28].

Preoperative use of corticosteroids is believed to contribute to several postoperative complications which include impaired bronchial healing [62]. In a study by Algar et al. 2001, patients with preoperative steroid therapy were associated with higher risk of BPF (p < 0.001) [32]. This same study found hypoalbuminemia to also be related to higher risk of BPF (p < 0.017) [32]. Hypoalbuminemia has a negative effect on the healing process, and in order to decrease the BPF risk, an albumin level above 3.5 mg/dl is the goal [63]. Patients requiring a pneumonectomy are usually very catabolic and nutritional assessment is essential in their management [1]. Metabolic alterations induced by the lung cancer tumor affects the nutrition in these patients [64]. These alterations lead to cachexia syndrome with higher levels of the proinflammatory cytokines interleukin-6 and tumor necrosis factor and lower levels of albumin [64]. Malnutrition increases the risk of 90-day mortality rate, postoperative infection and length of hospital stay after a pneumonectomy and a thorough preoperative evaluation is crucial [64].

### **4. Pathophysiology: clinical features and diagnosis**

#### **4.1 Early/acute bronchopleural fistula**

An early BPF has a peak incidence within 8 to 12 days after surgery but can occur at any time in the postoperative period [59]. Surgical closure of the BPF is the cornerstone of management. If a BPF is seen within the first 4 days after surgery, it requires exploration as it is likely due to a mechanical failure of the bronchial stump [59]. Early BPFs are normally approached urgently through the previous thoracotomy incision. An acute BPF can be life-threatening due to asphyxiation from pulmonary flooding or tension pneumothorax due to a massive air leak [59, 65, 66] (**Figure 2**). Acute BPF should be suspected in patients who present with fever, dyspnea, subcutaneous emphysema, excessively productive cough of purulent fluid, hypotension, trachea or mediastinal shift, disappearance, or reduction of pleural effusion on the chest radiograph or persistent air leak [25, 59, 65]. Chest radiography monitors the efficacy of BPF therapy and plays an essential role in evaluating the possibility of a BPF after a lung resection [2]. These symptoms appearing should raise the index of suspicion and quick and accurate diagnosis must be made before there is an overwhelming amount of aspiration into the remaining lung [25].

#### **4.2 Late/chronic bronchopleural fistula**

Late bronchopleural fistula present in the postoperative period more than 14 days [59]. The subacute and chronic forms present with more insidious symptoms and is characterized by fever, malaise, wasting, minimally productive cough, dullness to percussion on the affected side and reduced air entry with progressive clinical deterioration and varying levels of respiratory compromise [2, 59, 65]. A late BPF is often seen in debilitated or immunocompromised patients with many comorbidities [59]. In the chronic form that is associated with empyema, there is fibrosis of the mediastinum and pleural space preventing the mediastinal shift [59, 65].

Causes of late BPF include foreign body aspiration, refractory infection, chemotherapy and radiotherapy, and blunt chest trauma [67]. The time of interval is 2 months to 20 years between the surgery, therapy or injury and the onset of the late BPF [67].

#### **Figure 2.**

*Axial lung window after right pneumonectomy with large pneumothorax with evidence suggesting communication of the bronchial stump and pleural space. Case courtesy of Radswiki, Radiopaedia.org, rID: 11262.*

#### *Bronchopleural Fistula after Pulmonary Resection: Risk Factors, Diagnoses and Management DOI: http://dx.doi.org/10.5772/intechopen.100209*

In late BPF, due to the relatively stable mediastinal structures, conservative treatment is accepted by many investigators as the first step. Closure of the bronchial fistula with endoscopic treatment should be considered [67]. Proper antimicrobial coverage is mandatory along with proper nutrition with patients frequently requiring parenteral or enteral feeding [65]. Aggressive nutritional support and physical rehabilitation should be started early to optimize patients and enhance their recovery [65]. If surgery is indicated for a late BPF, the previous transthoracic approach may be unsafe due to fibrosis with associated inflammation with risk of bleeding and injury to vital structures [68, 69]. With a median sternotomy, approaching well vascularized, healthy, virgin tissues to reach the carina and bronchi may be preferrable and necessary. The advantages to the transsternal approach for BPF closure are avoidance of an inflamed operative field, scarring and adhesions in previous surgical fields and deformities of the thorax with thoracoplasty [68, 69]. The disadvantage of this approach is the infected empyema space is not managed at the time of closure. Previous cardiac surgery is not recommended for this type of approach [68, 69].

Once a BPF is suspected, a Computerized Tomography (CT) Scan with intravenous contrast to map the vasculature and better define the air-fluid levels and the peripheral rind enhancement is necessary [70]. This scan will identify the fistulous tract and will allow evaluation of the potential causes of BPF (i.e. recurrent tumor, staple line dehiscence, pneumonia, abscess, devascularized stump). It will also be simultaneously used to define the anatomic relationship of the adjacent mediastinal structures, vasculature, and diaphragm. A large fistulous tract can be clearly identified and a vigilant search must take place to look for subtle signs of a small BPF such as a change in the appearance of pre-existing pleural air-fluid levels and extraluminal air bubbles adjacent to the bronchial stump. Care must be taken to ensure while the patient is lying flat during the scan that they do not aspirate the pleural fluid through the BPF to the healthy lung [70].

All patients should undergo diagnostic bronchoscopy whether the BPF diagnosis is apparent radiographically or clinically [25]. A large fistula can be visualized but smaller 1 to 2 mm fistulas may be difficult to recognize [25]. Bronchoscopy provides information about the tissue at the level of the stump and condition of the remaining bronchial stump and can assist in deciding definitive repair [25].

#### **5. Management of BPF**

Management varies according to the individual patient, but the importance of addressing the risk of contralateral aspiration pneumonia and tension pneumothorax by drainage of the pleural space at time of diagnosis has to be emphasized [69]. The most important action when an acute BPF is suspected is protecting the contralateral lung from spillage of pleural fluid [2]. The primary principle is drainage of the pleural space by chest tube thoracostomy and care should be taken to place the chest tube above the previous thoracotomy incision as the diaphragm will be elevated with the normal thoracic remodeling that occurs after pneumonectomy [25, 59, 71, 72]. Pleural fluid should be sent for total protein, complete blood cell count, glucose, cytology, lactate dehydrogenase, triglycerides, gram stain and culture to evaluate for pleural infection [59]. Although integral for drainage, the chest tube can predispose the pleural space to infection and function as a foreign body [59]. Connecting the chest tube to a digital chest drainage system allows for more accurate and objective assessment of air flow and larger flow values and trend evaluation would provide more detailed information about the size and severity of the BPF [73]. For patients who are mechanically ventilated, the chest tube can

be used for occlusion during the inspiratory phase or to add positive intrapleural pressure during the expiratory phase [59]. These interventions decrease BPF during inspiration and decrease air leak during expiration to maintain positive end-expiratory pressure (PEEP) [59].

#### **5.1 Acute failure of the bronchial stump**

Acute failure of the bronchial stump is usually due to bronchial stump dehiscence and expeditious surgical repair with this single-staged intervention is recommended once clinical stabilization is achieved [71, 74, 75]. Given the relative integrity of the tissue, early stage of the infectious process, minimal pleural contamination and no problematic residual space, early reoperation is warranted to reestablish an airtight stump [25, 71, 74, 75]. Exploration with surgical revision by posterolateral thoracotomy with selective intubation and lung isolation of the contralateral mainstem bronchus to prevent further spillage of the remaining lung is recommended [25, 71, 75]. The fistula, if not readily visible can be identified with the assistance of positive pressure ventilation while covering the bronchial stump with irrigation [25]. The pleural space should be completely debrided and irrigated to remove all necrotic tissue [25]. The bronchial stump is refashioned and carefully dissected to decrease trauma to the blood supply [25, 71]. Measured from the carina, all efforts are made to made for the final stump to be less than 1 cm in length [25] (**Figure 3**). The stump may be reclosed with a stapler if their remains sufficient length on initial exploration. In cases where there is too much inflammation to allow stapling, the bronchial stump is mobilized and reclosed with interrupted monofilament sutures [25, 71]. A balance between avoiding too much exposure that may damage blood supply and exposing enough bronchus to avoid tension on the closure much be achieved [25].

#### **5.2 Transposition of muscle flaps to treat BPF**

Using a vascularized tissue to reinforce the suture line is the most important aspect of closure [25, 76]. Stump coverage was previously discussed as a preventive measure for BPF. The objective in treating a BPF with vascularized tissue is to obliterate the postpneumonectomy pleural space [25, 71, 75, 77]. Deciding which muscle flap to use depends on which muscle was preserved or damaged from the previous thoracotomy and the amount of space to be filled [71, 75, 77]. The most common muscles used in the pleural space to treat a BPF are serratus anterior, pectoralis major, pectoralis minor, latissimus dorsi, and intercostal muscles [25, 71, 75, 77, 78]. The latissimus dorsi is the most reliable and largest muscle but

#### **Figure 3.**

*A. The bronchial stump should be less than 1 cm. After inspection, if there is enough length on the stump, it can be closed with a stapling device. B. With too much inflammation, the stump may need to be sutured closed. (Sugarbaker D, Bueno R, Burt B, et al, editors. Adult chest surgery. 3rd edition. New York: McGraw-Hill Education; 2020; with permission).*

*Bronchopleural Fistula after Pulmonary Resection: Risk Factors, Diagnoses and Management DOI: http://dx.doi.org/10.5772/intechopen.100209*

may not be sufficient to obliterate the postpneumonectomy cavity if it was already divided in the original thoracotomy [77, 78]. The greater omentum consists of a large fold of peritoneum with excellent blood supply and antibacterial effect, lymphoid tissue, and fat [76, 78]. Using large muscles as the latissimus dorsi, greater omentum and serratus anterior has the advantage to contribute bulk to fill some of the dead postpneumonectomy space sugar [76–78]. In a study by Mazzella et al. 2017, fourteen patients with early BPF were treated with surgical repair of the bronchial stump via thoracoscopy (2) or thoracotomy (12) with omentum and fibrin glue (2) parietal pleural (3), intercostal muscle (1) or pericardial patch (2) with no recurrence of BPF after surgery [79].

#### **5.3 Clagett window and eloesser flap**

Treating a BPF with empyema and sepsis may require an Eloesser flap for patients too debilitated or too ill for a decortication or prolonged procedure involving muscle flaps [25, 80, 81]. The difference between the Clagett open-window thoracostomy (OWT) procedure and Eloesser flap is that the Clagett procedure is larger than the Eloesser flap and the Clagett window is temporary to allow complete drainage of purulent drainage in the pleural space [80] (**Figure 4**). The Eloesser flap creates a permanent drainage window in the pleural space [80].

#### *5.3.1 Clagett procedure*

In 1963, Clagett and Geraci described a technique as a two-step procedure for the management of postpneumonectomy empyema [81, 82]. This procedure combined an open-window thoracostomy pleural drainage with repetitive irrigation of the infected cavity with obliteration of the space with antibiotic fluid without direct fistula closure [2, 25, 81–84]. The procedure resulted in recurrences of fistulization and prolonged hospitalization and significant mortality. This technique is rarely

**Figure 4.**

*(A) Clagett window and (B) Eloesser flap. (Sugarbaker D, Bueno R, Colson Y, et al, editors. Adult chest surgery. 2nd edition. New York: McGraw-Hill Education; 2015; with permission).*

used and has been modified with initial bronchial stump closure with muscle transposition described earlier [2, 25, 80–84].

Once the BPF is closed and buttressed with muscle transposition, diluted wet povidone-iodine (Betadine) dressings are placed in the thorax and changed every 48 hours in the operating room [81, 83, 84]. This is done for approximately 4 to 6 days until the muscle flap is adherent to the bronchial stump and adjacent mediastinum [81, 83, 84]. Then the pack is changed in the patient's room 3 to 4 times a day. When health granulation is present in the pleural space, the entire cavity is filled with antibiotic solution selected to tailor culture and sensitivity results [25, 81, 83, 84]. In multiple layers to avoid leakage of fluid, the chest is then closed [25, 81, 83, 84].

The modified Clagett procedure involves daily intracavitary dressing changes, lasting for a long period of time and may not allow chest closure. Other ways to accelerate wound healing process were investigated [85]. Wound vacuum-assisted closure (VAC) therapy has recently been evaluated and used in patients with complex infected wounds without the OWT [86]. Bacterial proteinases are microorganisms and play a pathogenic role in an infected wound by consuming oxygen and nutrients that are required for tissue repair [87]. Reducing the bacterial proteinase load in a wound would allow the body to heal [87]. The VAC allows topical solutions to be cyclically flushed into the foam dressing before removal under negative pressure that irrigates, cleans, and removes infectious material from the pleural space [85, 87]. This is done without OWT, decreasing postoperative pain [88]. Recent studies show that as an adjunct to standard therapy, the VAC can decrease pain, hospital length of stay and morbidity in patients with complicated postoperative empyema [85, 88].

#### *5.3.2 Eloesser flap*

The Eloesser Flap OWT continues to evolve. A "H" or "U" shaped incision is made above the previous incision over the dependent portion of the space [25, 80]. A segmentary resection of one or two ribs are removed to obtain a window and limit the tendency of the opening to contract and close [25, 79, 80]. Necrotic tissue is debrided and edges of the flap are sutured directly to the parietal pleura with absorbable interrupted sutures to create an epithelized tract which encourages healing and maintains window patency [25, 79, 80]. The window should be not too far inferiorly which may interfere with the diaphragm and not too posterior that would be difficult for the patient to manage [25, 79, 80]. Using moistened gauze, dressing changes are performed until the cavity is decontaminated. Care is taken to prevent cardiac tamponade by excessive gauze inserted in the cavity [25, 79, 80]. The thoracostomy is closed with a thoracomyoplasty when clinical conditions suggest correct timing. In the chest cavity, healthy granulation tissue, improved clinical condition, closure of the bronchial stump and negative cultures of the chest cavity all suggest proper timing [25, 79, 80].

#### **6. Endoscopic treatment of bronchopleural fistula**

#### **6.1 Biological glue**

Many different biological glues for endoscopic BPF closure are available. Fibrinbased, albumin-glutaraldehyde tissue adhesive, and cyanoacrylate-based glues are the most common [2, 83]. Application technique is performed by a catheter inserted through the flexible bronchoscope and placed above the fistula [2, 83]. The glue is injected into the fistula and creates a plug after a few seconds that occludes the

*Bronchopleural Fistula after Pulmonary Resection: Risk Factors, Diagnoses and Management DOI: http://dx.doi.org/10.5772/intechopen.100209*

fistula with instantaneous cessation of air leak expected [2, 83]. Some prefer glue injection with a 21G needle due to less glue displacement and more effective closing of the BPF. This procedure may need to be repeated and endoscopic surveillance and close clinical monitoring is important for signs of failure [2, 83].

Cardillo et al. 2015, reported patients with BPF sized 1 cm or less with a viable bronchial stump were treated endoscopically [89]. The cure rate with endoscopic treatment was 92.3% in very small fistulas <2 mm with mechanical abrasion of the fistula. Cure rate was 71.4% in small fistulas >2 mm and < 3 mm with submucosal injection of 0.5 to 2 mL polidocanolhydroxypolyethoxydodecane at the fistula. This liquid surfactant causes endothelial cell lysis. It induces sclerosis and acts on the venous endothelium via interferences with cell membrane lipids. Cure rate with intermediate fistulas >3 mm and < 6 mm was 80%. Treatment was with n-butyl cyanoacrylate glue injected into the fistula. This mechanically occludes the fistula causing proliferation of the bronchial mucosa and a local inflammatory reaction. Morbidity and mortality rates were 5.8% [89].

#### **6.2 Endobronchial valves**

Endobronchial valves (EBV) have been available since 2003 and were originally developed for the reduction of lung volume in patients with emphysema [90, 91]. They were first described by Snell et al., 2005 for BPF [92]. Introduced through a flexible bronchoscope, EBV have a unidirectional valve to prevent airflow into the fistula and will result in atelectasis and collapse of the fistula [90, 91, 93]. This results in decreased or absent air leak. The process of recovery would lead to resolution of the shunt, fibrosis, and eventual extraction of the EBV [90, 91, 93]. Complete elimination of air flow through the BPF does not always occur and does not mean the EBV is unsuccessful. Decreased flows may bring the rate below critical rate flows and allow for fistula healing [91].

#### **6.3 Amplatzer device closure**

Many small fistulas (<3 mm) spontaneously heal or heal with glue placed endoscopically [94, 95]. Treatment for BPF endoscopically can bridge to control infection until a patient is able to able to undergo surgical repair [90, 92] (**Figure 5**). Amplatzer

#### **Figure 5.**

*Amplatzer Muscular VSD Occluder 8mm x 7mm placed to occlude the right mainstem bronchopleural fistula. Image courtesy of Dr. Tarek Dammad, Orlando, Florida.*

device is normally used for transcatheter closure of atrial septal defects. This device can contribute to intrabronchial granulation tissue and has good biocompatibility [94, 95]. The tissue growth reduces the risk of displacement. The waist of the Amplatzer device is placed inside the fistula and the two discs are placed at the distal and proximal ends of the fistula [94, 95]. Fruehter et al. 2011 treated nine patients with Amplazter device with BPF and the fistula was successfully closed [96]. After nine months, the results were maintained [96].

#### **7. Conclusion**

Improvements in thoracic surgery have decreased the incidence of BPF but mortality remains high. Proactive approaches to risk management and mitigating potential causes for increased chance for BPF preoperatively and intraoperatively are essential to improved outcomes. Expeditious surgical repair for acute BPF, along with new therapies with wound vacuum-assisted closure (VAC) therapy and endoscopic options for small fistulas may all expedite closure of BPF and improve survival.

#### **Conflict of interest**

The author declares no conflict of interest.

#### **Thanks**

To my colleagues: Dr. Joseph Boyer, Dr. Nayer Khouzam, Dr. George Palmer and Dr. Marcello DaSilva at AdventHealth Orlando, Florida, U.S.A. and to Dr. Steve Talbert at the University of Central Florida. You all have taught me so much, for so many years, and I sincerely thank you.

#### **Author details**

Kristina Jacobsen Division of Cardiothoracic Surgery, AdventHealth Hospital, Orlando, FL, USA

\*Address all correspondence to: kristina.jacobsen@adventhealth.com

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Bronchopleural Fistula after Pulmonary Resection: Risk Factors, Diagnoses and Management DOI: http://dx.doi.org/10.5772/intechopen.100209*

#### **References**

[1] Skekar K, Foot C, Fraser J, Ziegenfuss M, Hopkins P, Windsor M. Bronchopleural fistula: An update for intensivists. Journal of Critical Care 2010; 25: 47-55.

[2] Dal Agnol G, Vieira A, Oliveria R, Antonia P, Figueroa U. Surgical approaches for bronchopleural fistula. Shanghai Chest 2017;1: 1-14.

[3] Fuso L, Varone F, Nachira D, Leli I, Salimbene I, Congedo M, et al. Incidence and management of postlobectomy and pneumonectomy bronchopleural fistula. Lung 2016; 194: 299-305.

[4] Tokunaga Y, Kita Y, Okamoto T. Analysis of risk factors for bronchopleural fistula after surgical treatment of lung cancer. Ann Thorac Cardiovasc Surg 2020; 26: 311-319.

[5] Okuda M, Go T, Yokomise H. Risk factor of bronchopleural fistula after general thoracic surgery: review article. General Thorac and Cardiovas Surg 2017; 65: 679-685.

[6] Marques P, Andrade G, Granadas J, et al. Iatrogenic Bronchopleural Fistula. Cureus 2020;12:1-8.

[7] Louie B, Wilson J, Kim S, Cerfolio R, Park B, Farivar A, et al. Comparison of VATS and robotic approaches for clinical stage I and II NSCLC using the STS database. Ann Thorac Surg. 2016;102:917-924.

[8] Mei J, Guo C, Xia L, Liao H, Pu Q, Ma L, et al. Long-term survival outcomes of video-assisted thoracic surgery lobectomy for stage I-II nonsmall cell lung cancer are more favorable than thoracotomy: A propensity scorematched analysis from a high-volume center in China. Transl Lung Cancer Res 2019;8:155-166.

[9] Liberman M, Cassivi S. Bronchial stump dehiscence: Update on prevention and management. Semin Thorac Cardiovasc Surg 2007; 19:366-373.

[10] Sirbu H, Busch T, Aleksic I, Schreiner W, Dalichau H. Bronchopleural fistula in the surgery of non-small cell lung cancer: Incidence, risk factors, and management. Ann Thorac Cardiovasc Surg 2001; 7: 330-336.

[11] He J, Xu X. Thoracoscopic anatomic pulmonary resection. J Thorac Dis 2012; 4: 520-547.

[12] Birdas T, Morad M, Okereke I, Rieger K, Kruter L, Mathur P, et al. Risk factors for bronchopleural fistula after right pneumonectomy: Does eliminating the stump diverticulum provide protection? Ann Surg Oncol 2012; 19:1336-1342.

[13] Elrakhawy H, Alassal M, Shaalan A, Awad A, Sayed S, Saffan M. Impact of major pulmonary resections on right ventricular function: Early postoperative changes. Heart Surgery Forum 2018; 21: 9-17.

[14] Hackett S, Jones R, Kapila R. Anesthesia for pneumonectomy. BJA Education 2019; 19: 297-304.

[15] Darling G, Abdurahman A, Yi Q, Johnson M, Waddell T, Pierre A, et al. Risk of a right pneumonectomy: Role of a bronchopleural fistula. Ann Thorac Surg 2005;79:433-437.

[16] Watanabe S, Asamura H. Lymph node dissection for lung cancer. Significance, strategy, and technique. J Thorac Oncol 2009;4: 652-657.

[17] Ray M, Smeltzer, M, Faris N, Osarogiagbon R. Survival after mediastinal node dissection, systematic sampling, or neither for early stage NSCLC. J Thorac Oncol 2020;15:1670-1681.

[18] Darling G, Allen M, Decker P, Ballman K, Malthaner R, Inculet R, et al. Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: Results of the ACOSOG Z0030 trial. J Thorac Cardiovasc Surg 2011;141:662-670.

[19] Lardinois D, DeLeyn P, Schil P, Porta R, Waller D, Passlick B, et al. ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer. Eur J Cardiothorac Surg 2006;30: 787-792.

[20] Mammana M, Marulla G, Zuin Z, Perissinotto E, Camacchio G, Franceschi E, et al. Postpneumonectomy bronchopleural fistula: analysis of risk factors and the role of bronchial stump coverage. Surgery Today 2020;50:114-122.

[21] Benhamed L, Bellier J, Fournier C, Akkad R, Mathieu D, Kipnis E, Porte H. Postoperative ischemic bronchitis after lymph node dissection and primary lung cancer. Ann Thorac Surg 2011;91:355-360.

[22] [22].Wright C, Wain J, Mathisen D, Grillo H. Postpneumonectomy bronchopleural fistula after sutured bronchial closure: Incidence, risk factors, and management. J Thorac and Cardiovasc Surg 1996;112:1367-1371.

[23] Cariata A, Piromalli E, Taviani M. Postpneumonectomy bronchial stump recurrence and bronchopleural fistula. Asian Cardiovasc & Thorac Annals 2012; 20: 439-442.

[24] Algar F, Alvarez A, Aranda J, Salvatierra A, Baamonde C, Lopez-Pujol F. Predication of early bronchopleural fistula after pneumonectomy: A multivariate analysis. Ann Thorac Surg 2001;72:1662-1667.

[25] Sugarbaker D, Bueno R, Burt B, Growth S, Loor G, Wolf A, Williams M, Adams A. Sugarbaker's adult chest surgery. 3rd ed. New York: McGraw Hill Education, c2020.

[26] Hu X, Duan L, Jiang G, Wang H, Liu H, Chen C. A clinical risk model for the evaluation of bronchopleural fistula in non-small cell lung cancer after pneumonectomy. Ann Thorac Surg 2013;96:419-424.

[27] Prange H: LaPlace's law and the alveolus. A misconception of anatomy and a misapplication of physics. Adv Physiol Educ 2003;27:34-40.

[28] Asamura H, Naruke T, Tsuchiya R, Goya T, Kondo H, Suemasu K. Bronchopleural fistulas associated with lung cancer operations. J Thorac Carciovasc Surg 1992;104: 1456-1464.

[29] Potaris K, Kapetanaksi E, Papamichail K, Midvighi E, Verveniotis A, Parissis F, et al. Major lung resections using manual suturing versus staplers during fiscal crisis. Int Surg 2017;102:198-204.

[30] Moura V, Lamdin E, Ferraz F, Turatti R, Jaqueta C, Leme P. Modified method for bronchial suture by Ramirez Gama compared to separate stitches suture: experimental study. Rev. Col Bras Cir 2014; 41: 188-192.

[31] Ucveta A, Gursova S, Sirzaia S, Erbavcub A, Ozturka A, Celana K, et al. Bronchial closure methods and risks for bronchopleural fistula in pulmonary resections: how a surgeon may choose the optimum method. Interact Cardiovasc Thorac Surg 2011; 12: 558-562.

[32] Algar F, Alvarez A, Aranda J, Salvatierra A, Baamonde C,

*Bronchopleural Fistula after Pulmonary Resection: Risk Factors, Diagnoses and Management DOI: http://dx.doi.org/10.5772/intechopen.100209*

Lopez-Pujol F. Prediction of early bronchopleural fistula after pneumonectomy: A multivariate analysis. Ann Thorac Surg 2001;72:1662-1667.

[33] Asamura H, Kondo H, Tsuchiya R. Management of the bronchial stump in pulmonary resections: a review of 533 consecutive recent bronchial closures. Eur J Cardiothorac Surg 2000;17:106-110.

[34] Habaut J, Baron O, Al Habash O, Despins P, Duveau D, Michaud J. Closure of the bronchial stump by manual suture and incidence of bronchopleural fistula in a series of 209 pneumonectomies for lung cancer. Eur J Cardiothorac Surg. 1999;16: 418-423.

[35] [35].Makidono K, Miyata Y, Ikeda T, Tsutani Y, Kushitani K, Takeshima Y, et al. Investigation of surgical technique for bronchial stump closure after lobectomy in animal model. Gen Thorac and Cardiovasc Surg 2020;68: 609-614.

[36] Panagopoulosa N, Apostolakisa E, Koletsisa E, Prokakisa C, Hountisb P, Sakellaropoulosc G, et al. Low incidence of bronchopleural fistula after pneumonectomy for lung cancer. Interact Cardiovasc Thorac Surg 2009;9: 571-575.

[37] Cerfolio R, Bryan A, Yamamuro M. Intercostal muscle flap to buttress the bronchus at risk and the thoracic esophageal-gastric anastomosis. Ann Thorac Surg 2005;80:1017-1020.

[38] Kesler K, Hammoud Z, Rieger K, Kruter L, Yu M, Brown J. Carinaplasty airway closure: A technique for right pneumonectomy. Ann Thorac Surg 2008;85:1178-1186.

[39] Goyal V, Gupta B, Sharma S. Intercostal muscle flap for repair of bronchopleural fistula. Lung India 2015;32: 152-154.

[40] Sfyridis P, Kapetanakis E, Baltaviannis N, Bolanos N, Anagnostopoulos D, Markogiannakis A, et al. Bronchial stump buttressing with an intercostal muscle flap in diabetic patients. Ann Thorac Surg 2007;84:967-972.

[41] Caushi F, Quirjako G, Skenduli I, Xhemalaj D, Hafizi H, Bala S, et al. Is the flap reinforcement of the bronchial stump really necessary to prevent bronchial fistula? J Cardiothorac Surg 2020; 15:1-7.

[42] Taghavi S, Marta G, Lang G, Seebacher G, Winkler G, Schmid K, et al. Bronchial stump coverage with a pedicled pericardial flap. An effective method for prevention of postpneumonectomy bronchopleural fistula. Ann Thorac Surg 2005;79:284-288.

[43] Cerfolio R, Bryan A, Jones V, Cerfolio R. Pulmonary resection after concurrent chemotherapy and high dose (60 Gy) radiation for non-small cell lung cancer is safe and may provide increased survival. Eur J Cardiothorac Surg 2009;35: 718—723.

[44] Park J, Eom J, Choi S, Kim Y, Kim E. Use of a serratus anterior musculocutaneous flap for surgical obliteration of a bronchopleural fistula. Interact Cardiovasc Thorac Surg 2015;20: 569-574.

[45] Botianu P. Current indications for the intrathoracic transposition of the omentum. Botianu J Cardiothorac Surg 2019;14:1-6.

[46] Jiang F, Huang J, You O, Yuan F, Yin R, Xu L. Surgical treatment for bronchopleural fistula with omentum covering after pulmonary resection for non-small cell lung cancer. Thorac Cancer 2013;4:249-253.

[47] D'Andrilli A, Ibrahim M, Andreetti C, Ciccone A, Venuta F, Rendina E. Transdiaphragmatic harvesting of the omentum through thoracotomy for bronchial stump reinforcement. Ann Thorac Surg 2009;88:212-215.

[48] Lia S, Fana J, Zhoub J, Renb Y, Shena C, Che G. Residual disease at the bronchial stump is positively associated with the risk of bronchoplerual fistula in patients undergoing lung cancer surgery: a meta-analysis. Interact Cardiovasc Thorac Surg 2016;22: 327-335.

[49] Wind J, Smit E, Senan S, Eerenberg J. Residual disease at the bronchial stump after curative resection for lung cancer. Eur J Cardiothorac Surg 2007;32: 29-34.

[50] Li S, Fan J, Liu J, Zhou J, Ren Y, Shen C, Che G. Neoadjuvant therapy and risk of bronchopleural fistula after lung cancer surgery: A systematic meta-analysis of 14,912 patients. Japanese J Clinical Onc 2016;46: 534-546.

[51] Kim A, Boffa D, Wang Z, Detterbeck F. An analysis, systematic review, and meta-analysis of the perioperative mortality after neoadjuvant therapy and pneumonectomy for non–small cell lung cancer. J Thorac Cardiovasc Surg 2012;143:55-63.

[52] Clark J, Cooke D, Brown L. Management of complications after lung resection. Prolonged air leak and bronchopleural fistula. Thorac Surg Clin 2020;30:347-358.

[53] Chargari C, Riet F, Mazevet M, Morel E, Lepechoux C, Deutsch E. Complications of thoracic radiotherapy. Presse Med 2013;42:342-351.

[54] VandePas J, Roozendaal L, Wanders S, Custers F, Vissers Y, DeLoos E. Bronchopleural fistula after concurrent chemoradiotherapy. Adv in Radiation Onc 2020;5: 511-515.

[55] Gonzalez M, Litzistorf Y, Krueger T, Popeskou S, Matzinger O, Ris H, et al. Impact of induction therapy on airway complications after sleeve lobectomy for lung cancer. Ann Thorac Surg 2013;96:247-252.

[56] Deschamps C, Bernard A, Nichols F, Allen M, Miller D, Trastek V, et al. Empyema and bronchopleural fistula after pneumonectomy: Factors affecting incidence. Ann Thorac Surg 2001;72:243-248.

[57] Kopec S, Irwin R, Stoller J, Hollingsworth H: Sequelae and complications of pneumonectomy. Uptodate 2013, available from http:// www.bsgdtphcm.vn/thamkhao/ contents/UTD.htm?31/36/32329

[58] Matthews C, Goswami D, Ramchandani N, Huffard A, Reiger K, Young et al. The influence of airway closure technique for right pneumonectomy on wall tension during positive pressure ventilation: An experimental study. Semin Thoracic Surg 2020;32:1076-1084.

[59] Salik I, Vashisht R, Abramowicz A. Bronchopleural fistula. StatPearls [Internet] 2021. Available from https:// www.ncbi.nlm.nih.gov/books/ NBK534765/

[60] Toufektzian L, Patris V, Sepsas E, Konstantinou M. Does postoperative mechanical ventilation predispose to bronchopleural fistula formation in patients undergoing pneumonectomy? Interact Cardiovasc Thorac Surg 2015;21:379-382.

[61] Li S, Fan J, Zhou J, Ren Y, Shen C, Che G. Diabetes mellitus and risk of bronchopleural fistula after pulmonary resections: A meta-analysis. Ann Thorac Surg 2016;102:328-339.

[62] Kim H, Paik H, Kim S, Park M, Lee J. Preoperative corticosteroid use and early postoperative bronchial

*Bronchopleural Fistula after Pulmonary Resection: Risk Factors, Diagnoses and Management DOI: http://dx.doi.org/10.5772/intechopen.100209*

anastomotic complications after lung transplant. Korean J Thorac Cardiovasc Surg 2018; 51: 384-389.

[63] Suzuki M, Otsuji M, Saitoh Y, Iizasa T, Shibuya K, Sekine Y, et al. Bronchopleural fistula after lung cancer surgery. Multivariate analysis of risk factors. J Cardiovasc Surg 2002;42:263-267.

[64] Bagan P, Berna P, DeDominicis F, Pereira J, Mordant P, DeLaTour B, et al. Nutritional status and postoperative outcome after pneumonectomy for lung cancer. Ann Thorac Surg 2013;95:392-396.

[65] Lois M, Noppen M. Bronchopleural fistulas. An overview of the problem with special focus on endoscopic management. CHEST 2005; 128:3955-3965.

[66] Erwin F, Lakson G, Sarvasti D, Tahalele P. Spontaneous pneumothorax following bronchopleural fistula in geriatric patient: A case report and emergency management. J Widya Medika 2021; 3: 53-61.

[67] Zhang C, Pan Y, Zhang R, Wu W, Liu D, Zhang M. Late-onset bronchopleural fistula after lobectomy and adjuvant chemotherapy for lung cancer: A case report and review of the literature. Medicine 2019;98:1-5.

[68] Topcuogly M, Kayhan C, Ulus T. Transsternal Transpericardial approach for the repair of bronchopleural fistula with empyema. Ann Thorac Surg 2000;69:394-397.

[69] [69].Bal S, Ali K, Haridas B, Shrivastava G, Gupta S. Management of post pneumonectomy bronchopleural fistula: the transpericardial approach. J Vis Surg 2018;4:237-242.

[70] Gaur P, Dunne R, Colson Y, Gill R. Bronchopleural fistula and the role of contemporary imaging. J Thorac Cardiovasc Surg 2014;148:341-347.

[71] Teh E, West D. Bronchopleural fistula: prevention is still best. Shanghai Chest 2017;1:48.

[72] QV J, Chen G, Jiang G, Ding J, Gao W, Chen C. Risk factor comparison and clinical analysis of early and late bronchopleural fistula after non-small cell lung cancer surgery. Ann Thorac Surg 2009;88:1589-1593.

[73] Jacobsen K, Talbert S, Boyer J. The benefits of digital drainage system versus traditional drainage system after robotic-assisted pulmonary lobectomy. J Thorac Dis 2019; 11: 5328-5335.

[74] Cusmano G, Alifano M, Lococo F. Endoscopic and surgical treatment for bronchopleural fistula after major lung resection: an enduring challenge. J Thorac Dis 2019;11:S1351-S1356 .

[75] Bribriesco A, Patterson A. Management of postpneumonectomy bronchopleural fistula. From thoracoplasty to transsternal closure. Thorac Surg Clin 2018;28:323-335.

[76] Okada S, Shimomura M, Tsunezuka H, Ishihara S, Ishikawa N, Kameyama K, et al. One-stage closure of large bronchopleural fistula with pedicledlatissimus dorsi muscle flap after preemptive antibiotics: A case report. International J Surg Case Reports 2020;74:257-259.

[77] He Z, Shen L, Xu W, He X. Effective treatment of bronchopleural fistula with empyema by pedicled latissimus dorsi muscle flap transfer. Two case report. Medicine 2020; 99:41.

[78] Lu C, Feng Z, Ge D, Yuan Y, Zhang Y, Qi F, et al. Pedicle muscle flap transposition for chronic empyema with persistent bronchopleural fistula: Experience of a single clinical center in China. Surg Today 2016;46:1132-1137.

[79] Mazzella A, Pardolesi A, Maisonneuve P, Petrella F, Galetta D, Gasparri R, et al. Bronchopleural fistula after pneumonectomy: Risk factors and management, focusing on open-window thoracostomy. Semin Thorac Cardiovasc Surg 2018;30:104-113.

[80] Denlinger, C. Eloesser flap thoracostomy window. Oper Tech Thorac Cardiovasc Surg 2010;15:61-69.

[81] Pairolero P, Arnold P, Trastek V, Medland B, Kay P. Postpneumonectomy empyema. The role of intrathoracic muscle transposition. J Thorac Cardiovasc Surg 1990;99:958-968.

[82] Schneiter D, Cassina P, Korom S, Inci I, Al-Abdullatief M, Dutly A, et al. Accelerated treatment for early and late postpneumonectomy empyema. Ann Thorac Surg 2001;72:1668-1672.

[83] Azevedo I, Oliveira R, Ugalde P. Management of postpneumonectomy empyema and bronchopleural fistula. Shanghai Chest 2021;5:15.

[84] Zaheer S, Allen M, Cassivi S, Nichols F, Johnson C, Deschamps C, et al. Postpneumonectomy empyema: Results after the Clagett procedure. Ann Thorac Surg 2006;82:279-287.

[85] Saadi A, Perentes J, Gonzalez M, Tempia A, Wang Y, Demartines N, et al. Vacuum-assisted closure device: A useful tool in the management of severe intrathoracic infections. Ann Thorac Surg 2011;91:1582-1590.

[86] Haghshenasskashania A, Rahnavardia M, Yana T, McCaughan B. Intrathoracic application of a vacuumassisted closure device in managing pleural space infection after lung resection: Is it an option? Interact Cardiovasc Thorac Surg 2011;13: 168-174.

[87] Gabriel A, Shores J, Bernstein B, DeLeon J, Kamepalli R, Wolvos T, et al. A clinical review of infected wound treatment with vacuum assisted

closure® (V.A.C.®) therapy: Experience and case series. Int Wound J 2009; 6:1-25.

[88] Hoffman H, Neu R, Potzger T, Schemm R, Grosseri C, Szoke T, et al. Minimally invasive vacuum-assisted closure therapy with instillation (Mini-VAC-Instill) for pleural empyema. Surgical Innovation 2015;22: 235-239.

[89] Cardillo G, Carbone L, Carleo F, Galluccio G, DiMartino M, Giunti R, et al. The rationale for treatment of postresectional bronchopleural fistula: Analysis of 52 patients. Ann Thorac Surg 2015;100:251-257.

[90] Zo S, Song J, Kim B, Jeong B, Jeon K, Cho J, et al. Surgically intractable bronchopleural fistula treated with endobronchial valve insertion by isolating the tract with indigo carmine: A case report. Resp Med Case Reports 2020;29:100972.

[91] Gaspard D, Bartter T, Boujaoude Z, Raja H, Arya R, Meena N, et al. Endobronchial valves for bronchopleural fistula: Pitfalls and principles. Ther Adv Respir Dis 2017;11:3-8.

[92] Snell G, Holsworth L, Fowler S, Eriksson L, Reed A, Daniels F. et al. Occlusion of a broncho-cutaneous fistula with endobronchial oneway valves. Ann Thorac Surg 2005;80:1930-1932.

[93] Kalatoudis H, Nikhil M, Zeid F, Shweihat Y. Bronchopleural fistula resolution with endobronchial valve placement and liberation from mechanical ventilation in acute respiratory distress syndrome: A case study. Case Rep Crit Care 2017:3092457.

[94] Wu Y, He Z, Xu W, Chen G, Liu Z, Lu Z. The Amplatzer device and pedicle muscle flap transposition for the treatment of bronchopleural fistula with chronic empyema after lobectomy: Two

*Bronchopleural Fistula after Pulmonary Resection: Risk Factors, Diagnoses and Management DOI: http://dx.doi.org/10.5772/intechopen.100209*

case reports. World J Surg Onc 2021;19:1-7.

[95] Motus I, Bazhenov A, Basvrov R, Tsvirenko A. Endoscopic closure of a bronchopleural fistula after pneumonectomy with the Amplatzer occluder: A step forward? Interact Cardiovasc Thorac Surg 2020;30:249-254.

[96] Fruchter O, Kramer M, Dagan T, Raviv Y, Abdel-Rahman N, Saute M, et al. Endobronchial closure of bronchopleural fistulae using Amplatzer devices. Our experience and literature review. Chest 2011;139:682-687.

#### **Chapter 6**

## Surgical Challenges of Chronic Empyema and Bronchopleural Fistula

*Yu-Hui Yang*

#### **Abstract**

Chronic empyema has always been a clinical challenge for physicians. There is no standard procedure or treatment to deal with the situation, and multi-modality approach is often necessary. Surgical intervention plays a very crucial role in the treatment of chronic empyema. Since bronchopleural fistula is often seen in chronic empyema patients, therefore it should also be mentioned. In this chapter, the focus will be on the different treatment options, various surgical approaches, and the rationale behind every single modality. Certain specific entity will be included as well, such as tuberculosis infection, post lung resection empyema, and intrathoracic vacuum assisted closure system application. Even with the advancement of technology and techniques, chronic empyema management is still evolving, and we look forward to less traumatic ways of approach with better outcome in the future.

**Keywords:** Empyema, bronchopleural fistula, open window thoracostomy, VAC, Clagett procedure, thoracoplasty, muscle flap transposition

#### **1. Introduction**

Empyema is a common clinical problem to both pulmonary physicians and thoracic surgeons. It affected 65,000 patients annually in the US [1]. Thanks to the advent of antibiotics and continuous advancement of minimally invasive procedures, most acute empyema patients can now receive tube thoracostomy and/or video-assisted thoracoscopic surgeries (VATS) to alleviate the infection with good recovery [2]. Empyema, also known to be pleural empyema or thoracic empyema, is defined as infection in the pleural cavity. The most common scenario is that the patient has a prior or ongoing pneumonia which the infection has extended to the lung surface, causing a series of inflammation and infection response on the visceral pleura and therefore parietal pleura. The products of the infection then accumulate in the pleural space resulting in empyema. Some patients would develop pleuritic pain which they easily mistake it as muscle strains or sprains, so they tend to overlook the real problem and lead to delay diagnosis. There are also a lot of other reasons that can eventually cause empyema, such as trauma, invasive procedures (including thoracic operation), liver abscess, spinal abscess, mediastinitis (because in the vicinity of an infection source) or being transmitted through hematogenous route.

#### **2. Stages of empyema**

According to American Thoracic Society classification, empyema is divided into three stages (**Table 1**) [3, 4]. In the early stage of pleural cavity infection, some fibrin would develop in this avascular space along with some body fluid. It is often recognized as parapneumonic pleural effusion. At this exudative phase, most fluid in the pleural cavity can be drained by a chest tube. If the infectious process continues and the fluid accumulates, the fluid will become thicker with more fibrin deposition. This second stage is often characterized by loculated pleural effusion which makes it difficult to drain all effusion in different areas with a single chest tube. Patients with this true empyema stage often require surgical intervention to deloculate the effusion for complete drainage. Fibrinolytic agent is another option for non-surgical candidate. When the disease progresses, more and more fibrin pile up and the fluid becomes denser and denser. A thick peel will form to cover all contact surfaces, including lung, inner chest wall, diaphragm, and mediastinum. This final stage of empyema, organizing phase, will restrict lung expansion and hence reduce lung compliance. More aggressive treatment modalities should always be considered to avoid long-term lung function impairment.


#### **Table 1.**

*Stages of empyema.*

#### **3. Treatment principles**

Since empyema equals to infected pleural cavity, the primary goal is to treat the infection. There are a few recognized treatment principles to such disease. First, sterilization of the pleural space. Second, adequate drainage. Third, optimizing lung expansion and reducing potential pleural space. These principles will be explained in detail below.

#### **3.1 Sterilization of the pleural space**

Just like treating other infectious disease, removal of pus or necrotic tissue and antibiotics therapy are the two key components to successful treatment. In *Surgical Challenges of Chronic Empyema and Bronchopleural Fistula DOI: http://dx.doi.org/10.5772/intechopen.100313*

empyema, sterilization targets not only the pleural space but also the original infection source, such as pneumonia or liver abscess. To select effective antibiotics, obtaining cultures are important so that adjustment can be made according to susceptibility test after empirical antibiotics. Other effective ways to lower the pathogen colonization in the pleural cavity are removal of the infectious debri and irrigation. These procedures, debridement and irrigation, are often carried out during the surgery, either through VATS or thoracotomy. Although some doctors believe irrigation may result in unstable hemodynamics as capillary permeability increases due to transient bacteremia, the author thinks it is reasonable to do so as it is easier and faster to achieve sterilization. If the patient's blood pressure drops during the surgery, it is suggested to irrigate the pleural cavity with some diluted epinephrine with cautious monitoring. Since the patient's capillary permeability may increase, it is possible that the patient would develop tachycardia and hypertension if the medication is well-absorbed by the pleura.

#### **3.2 Adequate drainage**

Unlike airway, pleural cavity is a closed space. The fluid should be drained adequately to avoid further or repeated infection. A chest tube is sufficient for simple parapneumonic pleural effusion (stage I empyema) while complicated pleural effusion (stage II empyema) or organizing empyema (stage III empyema) often requires surgical intervention and a chest tube(s) after the surgery for adequate drainage.

#### **3.3 Optimizing lung expansion and reducing potential pleural space**

When the empyema reaches to its final stage --- organizing stage, the lung would become completely trapped and therefore poorly expanded. This not only leads to restrictive lung (impaired lung function), but also leaves a potential dead space in the pleural cavity. This space would possibly result in repeated infection. Therefore, the initial treatment goal of empyema should also include best pleural apposition to prevent chronicity. To achieve this, remove "peels" from the lung and other pleural surfaces. This surgical procedure is known as "Decortication." As long as it is feasible, removing all debri and resuming patients' optimal pulmonary function are always recommended. However, there could be exceptions that the lung fails to fill the pleural cavity. If this is the case, other measures should be taken to reduce the potential pleural space.

From a thoracic surgeon's point of view towards managing empyema, it is always "the earlier the easier." In an acute setting of empyema (stage I or II), most patients can be cured by tube thoracostomy or VATS [2]. This further emphasizes the fact that early diagnosis and early aggressive treatment to prevent chronicity are crucial. In addition, the choice of first intervention is important as well. According to the literature, failure of the first attempted procedure was an independent predictor of death [5]. As a result, operation is the most successful initial procedure in this study. More and more studies demonstrated good outcomes of early surgical intervention treating complex empyema [5, 6]. Furthermore, VATS decortication is found to be superior to open surgery in the management of primary empyema [7]. In the author's hospital, empyema is a surgical disease. Once the diagnosis is made, almost all patients need surgical consult for further treatment planning. All surgeons tacitly agree that VATS is the gold standard procedure to treat acute empyema in the author's institution.

There are still certain patients who will eventually continue to have the infection and enter to a chronic phase. Several causes of chronic empyema include delayed

diagnosis, retained hematoma in the pleural cavity, bronchopleural fistula with continuous airway secretion spillage, a large potential pleural space (e.g. post lung resectional empyema) which is prone to have repeated infection, and the patient is too ill to receive definite treatment at the initial acute phase. Among all the causes, the author thinks that retained hematoma in the pleural cavity is the most preventable cause of chronic empyema. Blood clots are perfect culture medium for bacteria, so it is important to avoid too much oozing when one performs VATS debridement and decortication on empyema patients, especially those who have liver cirrhosis, end stage renal disease, or other bleeding tendency. Adequate hemostasis and diluted epinephrine irrigation are helpful to prevent retained hematoma. If retained hematoma still happens, at least it is detectable from the drainage fluid. The drained fluid would be bloody initially then turned to dark brown and remained in this color without turning to light yellow. As one recognizes the sign of retained hematoma in the pleural cavity, it is often required to do another operation to remove all the blood clots to prevent chronic empyema.

#### **4. Treatment options**

In this section, the focus will be solely on the treatment options of chronic empyema and to which treatment principles that each option fits in.

When dealing with empyema, following the above mentioned three treatment principles is the key to success. Although the principles are the same in different stages, treatment strategies may vary, especially in the chronic stage. Treating chronic empyema is more complicated, more unpredictable, and therefore more challenging. It may require staged operations, different surgical approaches, and there is no standardized option. Before establishing treatment plan for chronic empyema patients, comprehensive understanding between each option is necessary.

#### **4.1 Optimizing lung expansion by decortication**

Decortication can be done either through VATS or thoracotomy. It is basically surgeon's preference. During the same surgery, debridement is also done so that non-viable tissue and debri are removed to achieve "cleaning" in the pleural cavity. In stage III empyema, the lung is always restricted by thickened "cortex," so freeing the lung by decortication can optimize lung expansion and reduce the potential pleural space. Choosing proper surgical instruments accelerates the procedure. In the author's experience, Roberts artery forceps or long Kelly forceps are best tools to separate the lung from the overlying "cortex." This separation process can be done sometimes with the operated lung ventilating so that the correct pleural plane is evident. If pleural apposition still cannot be achieved after decortication, make sure to check the lung surface again. There may be some remnant peel from the multilayered peel that restricts lung expansion. Sometimes the peel is extremely thick and firm. Using a scalpel cautiously to slit through the peel will aid in removal.

\*Fitting in the treatment principles sterilization of the pleural cavity and reducing potential pleural space by optimizing lung expansion.

#### **4.2 Optimizing lung expansion by other means**

To optimize lung expansion, there are several other ways, but none are as effective as decortication.

#### *4.2.1 Positive airway pressure*

Some of these patients are ventilator dependent while others are not. If they still require ventilator support, it is acceptable to increase positive end-expiratory pressure (PEEP) a little, by 1 or 2 cmH2O, to further expand the lung. If patients can be weaned off from ventilator successfully after the operation, a strategical management option is to delay extubation time by 0.5 to 1 day. This may also allow the lung to further expand.

\*Fitting in the treatment principle reducing potential pleural space by optimizing lung expansion.

#### *4.2.2 Negative pleural pressure*

Positive airway pressure expands the lung from internal while negative pleural pressure provides a tractive force externally. A suction pressure of −20 cmH2O is usually recommended with a traditional chest drainage system. Other modality that can create negative pressure in the pleural cavity is Vacuum-assisted closure (VAC) therapy. (see 4.4).

\*Fitting in the treatment principles drainage and reducing potential pleural space by optimizing lung expansion.

#### **4.3 Open window thoracostomy (OWT)**

#### *4.3.1 History of OWT*

OWT was first described by Robinson in 1916 and then revised by Leo Eloesser in 1935 which was also called Eloesser flap thoracostomy window [8]. However, the most adopted OWT is modified by Symbas and coworkers in 1971 as modified Eloesser flap [9].

#### *4.3.2 Rationale, advantage, and disadvantage of OWT*

This procedure, an open drainage method, is often saved as the last resort to treat chronic empyema, especially when the pleural infection is difficult to be managed by debridement and decortication. It is also a treatment option for critically ill patients who are too weak to receive decortication. As the name presents itself, OWT is to create a window through the patient's chest so serial dressing changes are feasible to clean the infected pleural cavity and therefore alleviate the septic condition. The advantage of OWT is that it is proved to be safe and effective [10]. On the other hand, it affects the patient's appearance and may cause chronic pain after chest wall resection. Some of the patients will need another surgery to close up the wound.

\*Fitting in the treatment principles sterilization of the pleural cavity and drainage.

#### *4.3.3 Surgical techniques and special considerations of OWT*

The most common use of OWT is modified Eloesser flap [11]. The window is usually created at the basal part of the hemithorax where most of the infected material accumulates (**Figure 1**). After confirming the chest CT image, an inverted U-shaped incision is made at this area. Electrocautery is used for dissection till the rib cage. In order to create a sufficient window, two or three

#### *Pleura - A Surgical Perspective*

ribs need to be resected. Then, the tongue-shaped muscular-cutaneous flap is folded inward and sutured to the diaphragm (**Figure 2**). The remaining wound edge is sutured to the pleura so that the window can be maintained for a period of time without spontaneous closure. It is also imperative that the window is large enough for the convenience of frequent wet packings. Another key point that must be mentioned is the timing of OWT creation. From the Massera et al. study [12], immediate OWT requires lesser time for the resolution of empyema comparing to the delayed OWT after prolonged chest tube drainage. As a result, the median OWT closure time (between performing and closing of OWT) of immediate OWT was 8 months shorter than that of delayed OWT. The timing of attempted closure should be carefully decided by the surgeon after a thorough evaluation of the empyema patient's condition. This includes free from recurrent disease, good recovery of the pleural cavity with coverage by healthy granulation tissue, the patient's general condition, and to a lesser degree by the normalization of inflammatory parameters [12, 13]. Methods of OWT closure please see 4.6.2 below.

**Figure 1.** *OWT. An OWT on the patient's left-side chest wall.*

*Surgical Challenges of Chronic Empyema and Bronchopleural Fistula DOI: http://dx.doi.org/10.5772/intechopen.100313*

#### **Figure 2.**

*Coronal view of the Eloesser flap window. Demonstrating the supposition of the skin surface of the inferiorly based soft tissue flap to the diaphragmatic surface. (Adapted from Denlinger [11].)*

#### **4.4 Vacuum-assisted closure (VAC) therapy**

#### *4.4.1 History of VAC therapy*

VAC is a negative pressure wound therapy that is widely used in acute and extended open wounds. The first case report of intrathoracic VAC therapy was published in 2006 [14]. Varker et al. managed a postlobectomy empyema patient with VAC device successfully after open debridement of the empyema cavity. In the next following decade, with the popularity of VAC therapy, it was proved that it is safe and efficient to fight against all kinds of intrathoracic infections [13, 15–17].

#### *4.4.2 Rationale, advantage, and disadvantage of VAC therapy*

VAC device is able to create a negative pressure wound environment that promotes wound healing by reducing edema, promoting granulation tissue formation and perfusion, and removing exudate and infectious material. As to treating chronic empyema, it is a useful tool to apply on an open wound such as an OWT after debridement of the pleural cavity (**Figure 3**). In the setting of intrathoracic VAC usage, it may reduce the duration and frequency of dressing changes necessary for spontaneous chest closure or a space filling procedure, reducing patient's

**Figure 3.** *Intrathoracic VAC therapy. VAC therapy is applied through the patient's OWT.*

discomfort, and resolving the infectious process faster [18]. When compared with conventional management of OWT, VAC therapy accelerates wound healing and helps re-expansion of residual lung parenchyma in patients with OWT [19]. In selected patients, applying Mini-VAC procedure can even avoid OWT by insertion of the ALEXIS (Applied Medical, Rancho Santa Margarita, CA, USA) wound retractor to create a similar window effect without resecting the ribs which preserves the chest wall integrity and avoids the consequences that OWT can cause (**Figure 4**) [20]. However, the biggest disadvantage of this device is that it is not suitable for everyone. VAC device should be used cautiously or be avoided on patients with bleeding tendency, presence of malignancy, or unstable hemodynamics. Because VAC creates a negative pressure environment, it may lead to continuous bleeding, promote cancer growth, or deteriorate hypotension. The reason why

#### **Figure 4.**

*Mini-VAC procedure. VAC therapy is applied through the ALEXIS wound retractor which creates a similar window effect without resecting the ribs.*

hypotension may develop is probably due to the negative pressure effect intrathoracically causing decreased cardiac output. Thus, intrathoracic application in older patients must be monitored closely and should be avoided on patients with poor cardiac function.

\*Fitting in the treatment principles drainage and reducing potential pleural space by optimizing lung expansion.

#### *4.4.3 Surgical techniques and special considerations of VAC therapy*

VAC therapy is designed to be applied on open wounds. To treat chronic empyema with VAC, an open chest wound or an OWT must be created during the surgical intervention. Some authors advocate leaving the thoracotomy wound open directly after the operation [13, 14] while others create an OWT to make dressing changes easier [17–19]. It is reasonable to decide on an individual basis depending on the size and depth of the residual pleural space. A large and deep residual pleural space is preferred for OWT. The advantage of OWT is that the chest will stay open for a longer period because of the inverted skin flap compared to just leaving the thoracotomy wound open. OWT would avoid the skin from healing before complete eradication of the infected pleural cavity. It is contraindicated to apply VAC on a dirty wound with necrotic tissue that has yet to be debrided. After adequate debridement in the pleural cavity, VAC sponges (GranuFoam) are inserted in the residual pleural space to fill the entire cavity. Placing the sponges directly in contact with exposed blood vessels, anastomotic sites, organs, or nerves are prohibited, except for the lungs. According to the literature [13, 21] and the author's personal experiences, VAC dressing can be safely applied directly on the visceral pleura or lung parenchyma without any complications. The negative pressure can be set at -50 mmHg from the start, and gradually increased to -125 mmHg if the patient does not have any discomfort. The dressing change should be done at least twice a week, and it can be performed at the bedside. During the VAC therapy period, the skin covered by the dressing should be well protected to prevent skin maceration problems. If negative pressure fails to be maintained due to significant air leak caused by bronchopleural fistula (BPF), combining a one-way valve may solve this issue [21].

When dealing with postpneumonectomy empyema (PPE), VAC therapy should be used carefully, especially for patients who develop the complication shortly after the initial surgery. This is because negative pressure would shift the mediastinum which may cause heart or great vessels herniation leading to obstructive shock or even cardiac arrest. On the contrary, if PPE is developed at a later stage, such events will not happen as the mediastinal shift has already completed and the patient's body has compensated it well.

#### **4.5 Empyema tube --- rationale, advantage, and disadvantage**

There are two scenarios where chronic empyema patients would need an empyema tube for long-term drainage. One is that the patient is too unstable and fragile to receive general anesthesia and adequate surgical intervention. To alleviate the septic condition, empyema tube (tube thoracostomy) can be placed to decrease the burden of infection until definite treatment can be initiated. Another scenario is that the chronic empyema is somehow localized in a small area without systemic infection. It is either a tube thoracostomy left after previous surgical intervention or a new chest tube inserted into this localized area for drainage if the patient is not a surgical candidate.

In the author's opinion, this treatment option is only reserved for those who are not able to receive other definite treatment because of the low success rate, and not all infected materials can be drained adequately. However, if adequate drainage can be achieved, the tube may be slowly retracted over a period of weeks to months while the infected space heals behind it [3].

\*Fitting in the treatment principle drainage.

#### **4.6 Filling the potential pleural space with different measures**

#### *4.6.1 Clagett procedure*

#### *4.6.1.1 History, rationale, advantage, and disadvantage of Clagett procedure*

Clagett procedure was first described by Clagett and Geraci in 1963 [22]. It is a method that obliterate the pleural cavity with antibiotic solution. As a precondition of the procedure, there must be no BPF and the pleural cavity should be sterilized by debridement and irrigation. In other words, if the patient has BPF and primary repair is impossible, Clagett procedure is not suitable for the patient. Nonetheless, this procedure has a good overall success rate in selected patients (no BPF at the time of the procedure), range from 81–100% [12, 23–25]. Those who fail from the procedure are mainly due to persistent or recurrent BPF.

\*Fitting in the treatment principle reducing potential pleural space.

#### *4.6.1.2 Surgical techniques and special considerations of Clagett procedure*

After confirming that there is no active BPF in the pleural cavity or it is firmly closed, antibiotic fluid can be instilled to fill the remaining pleural cavity after it is fully cleansed. DAB solution (gentamicin 80 mg/L, neomycin 500 mg/L, and polymyxin B 100 mg/L) is one of the antibiotic solution choices [23]. The combination of the fluid can be chosen according to the microbiological findings [26].

#### *4.6.2 Tissue flap transposition*

#### *4.6.2.1 Rationale, advantage, and disadvantage of tissue flap transposition*

Tissue flap transposition technique is frequently used in chronic empyema patients for the purpose of either closure of the BPF or OWT, and/or obliteration of the residual pleural space. It can also be used for the prophylactic reinforcement of a bronchial stump after major lung resection to avoid BPF formation. Because the flap tissue is full of mesenchymal cells, it can promote granulation tissue growing under good circulation and secure the bronchial stump as a backup layer. A bulky muscle flap is extremely helpful to reduce the residual pleural space while a smaller residual space only requires a smaller tissue flap. However, not every patient is medically fit for long-hour flap surgery especially the critically ill. A successful flap reconstructive surgery is determined by a well-perfused flap which is highly dependent on patients' stable hemodynamics.

\*Fitting in the treatment principle reducing potential pleural space.

#### *4.6.2.2 Surgical techniques and special considerations of tissue flap transposition*

Tissue flaps commonly used in chronic empyema are latissimus dorsi (LD) muscle flap (**Figure 5**), serratus anterior (SA) muscle flap, pectoralis major (PM) muscle flap, intercostal muscle flap, pedicled omental flap, and other free flaps. LD is the largest muscle among all chest wall muscles. Therefore, it is an ideal option for pleural cavity obliteration. However, if the patient has received a standard

**Figure 5.** *LD muscle flap. Harvest of the LD muscle flap to reinforce the PPE BPF closure.*

posterolateral thoracotomy previously, this muscle may have been compromised and hence not suitable. PM flap is another good alternative for it is the second largest chest wall muscles. Because of its anatomy and orientation, PM flap is particularly useful to obliterate the apical residual pleural space [3, 27]. Although SA flap and intercostal muscle flap are relatively small compared to LD and PM flaps, they can be sufficient to help accelerate BPF healing as long as the pedicle is healthy. Omental flap is another option if no chest wall muscle is available [28]. However, entering the peritoneal cavity may potentially spread the infection and complicate the situation. Sometimes the remaining pleural space is too big that only by combining two flaps will fill the space [27]. Free flap may also be considered in highly selected patients.

#### *4.6.3 Thoracoplasty*

#### *4.6.3.1 History, rationale, advantage, and disadvantage of thoracoplasty*

Thoracoplasty has a long history in the field of thoracic surgery. It was first described by Estlander in the late 19th century when tuberculosis was a troublesome pandemic without medical cure [29]. The original concept of this surgery is to collapse the chest wall to minimize the cavitary pleural space caused by mycobacterium. To achieve this goal, multiple ribs are resected resulting in loss of rigid chest wall configuration and therefore obliteration of the infected pleural space. Although it is an effective way to fill the potential pleural space, this procedure can cause significant morbidity, including chronic pain, chest wall deformity, thoracic spine scoliosis, limited ipsilateral shoulder range of motion, and finally resulting in poor quality of life.

\*Fitting in the treatment principle reducing potential pleural space.

#### *4.6.3.2 Surgical techniques and special considerations of thoracoplasty*

Thoracoplasty can be classified into three types, full, extended, and tailored thoracoplasty. Full thoracoplasty is defined as removing first 11 ribs to collapse the whole hemithorax. Extended thoracoplasty, on the other hand, is removing 7

**Figure 6.** *Thoracoplasty. Complete resection of the 4 right upper ribs. (Adapted from Lewis and Wolfe [31].)*

to 9 ribs while tailored thoracoplasty is removing fewer than 5 ribs at certain area [30]. Resection of 7 ribs can lead to approximately 50% reduction of the pleural space, and resection of 5 ribs results in 25% reduction (**Figure 6**) [31]. The key to a successful thoracoplasty is complete resection of the targeted ribs which means from the transverse process of the thoracic spine posteriorly to the costosternal joint anteriorly. In the modern era, this procedure is seldom conducted alone. Combining with muscle flap transposition is an effective alternative so that chest wall deformity can be less significant [32, 33].

Managing chronic empyema is art. There is no standardized option. Knowing the different measures in depth and applying each principle with these measures will certainly increase the success rate of treatment. Making a customized treatment plan according to the patient's physical condition, complications, and special requirements cannot be emphasized enough. There are special circumstances which will be introduced below for better understanding of how to put the different treatment options in use.

### **5. Special circumstances**

#### **5.1 Post-resectional empyema**

The main issue contributed by post-resectional empyema is that the residual pleural space is often large. The treatment strategy therefore should be emphasized on how to fill the space. If post-lobectomy empyema occurs in a delayed setting, the size of the residual pleural space would not be a concern because the pleural cavity should have been remodeled by diaphragm elevation, mediastinum shifting, and narrowing of the intercostal space over time. However, if post-resectional empyema happens in an acute phase when the remodeling has not been completed yet, different filling procedures should always be considered. For instance, if a patient who is medically fit for surgery develops a post-lobectomy empyema in a delayed phase, VATS or thoracotomy debridement and decortication are usually amenable to solving the problem.

Post-pneumonectomy empyema (PPE) is notorious for its high morbidity and mortality rate [12]. It is a challenging situation clinically, especially when BPF is present (**Figure 7**). According to the literature [12, 25, 30], approximately 65 to 84% PPE patients have BPF. Closure of the BPF is imperative or else spillage from *Surgical Challenges of Chronic Empyema and Bronchopleural Fistula DOI: http://dx.doi.org/10.5772/intechopen.100313*

**Figure 7.** *PPE with BPFs. (A) from the thoracoscopic view of the BPFs (B) from the bronchoscopic view of the BPFs.*

the infected cavity into the airway can cause pneumonia or even acute respiratory distress syndrome (ARDS). On the other hand, the secretion from the airway would also leak into the pleural space continuously and contaminate the cavity. After closing the BPF, as per treatment of other empyema, sterilization of the cavity with debridement, irrigation, parenteral antibiotics, and adequate drainage, the most important is effective obliteration of the remaining pleural space. Since the BPF is often failed by primary suture alone, covering the stump with pedicled muscle flap ensures secondary healing as well and obliteration the pleural space at the same time. For example, if a debilitated patient suffers from severe sepsis caused by late onset right-sided PPE with BPF, it is reasonable to lay out a staged surgical plan. First, do a tube thoracostomy and forbid the patient to lie in a left decubitus position to protect the contralateral lung. This first stage is for drainage and lung protection. Second, perform simple debridement, OWT, and primary BPF repair added on a buttressed intercostal muscle flap. Instead of frequent dressing changes after OWT, VAC therapy can be initiated under the circumstance without any contraindication. VAC dressings can be changed at least twice a week. After a period of aggressive treatment plus appropriate nutritional support, successful BPF closure, a clean pleural cavity covered with healthy granulation tissue, and improved physical status of the patient can be expected. The second stage is for sterilization of the pleural space and open drainage. The third stage is purely for filling. Choose an appropriate procedure, such as Clagett procedure, to obliterate the pleural cavity.

#### **5.2 Bronchopleural fistula (BPF)**

As mentioned in the last paragraph, BPF connects the bronchus to the pleural cavity leading to infection burden and possible respiratory distress. Life threatening events, such as ARDS or septic shock, must be managed as top priority. Successful closure of the BPF may prevent those critical situations from happening. As long as the patient's physical condition is suitable for intervention, attempts to close the BPF should be carried out as early as possible.

There are several ways to manage BPF, either bronchoscopically or surgically. Treatment choices mainly depend on patients' clinical status, duration before the development of BPF, and number and size of the BPF [30]. An algorithm for treatment of BPF at the European Oncologic Institute [34] (**Figure 8**) was created according to these principles. If the BPF occurs in an early setting (<14 days after surgery), surgical repair of the bronchial stump is always encouraged. In a delayed setting (>14 days after surgery), bronchoscopic application with sealants, fibrin glue, silver nitrate, coils, endobronchial stents, Endobronchial Watanabe Spigot, or atrial septal defect occluder device [35–38] can be used for small BPF size <8 mm or for patients who are physically unfit for surgery. As for BPF size >8 mm, patients

#### **Figure 8.** *Management of PPE BPF: EOI algorithm. (Adapted from Mazzella et al. [34].)*

who are fit for surgery, patients who had failure from other treatment strategies, surgical intervention is unavoidable. In addition to primary closure of the bronchial stump, muscle flap transposition to cover the sutured stump provides a good environment for secondary healing which may increase the success rate of closure. If the BPF is deemed to be closed during the operation, Clagett procedure may be considered after thorough cleansing of the infected pleural cavity. Since continuous spillage from the BPF may occur, therefore OWT is often a treatment option to enable frequent dressing changes to eliminate the infection.

#### **5.3 Malignant pleural empyema**

At times, malignant pleural effusion can be infected either through hematogenous or direct inoculation by invasive procedures. The treatment principles are essentially the same. Sterilization of the pleural cavity and adequate drainage are not difficult to achieve. Since the pleura tumor cells cannot be eradicated immediately by surgical procedures or medical treatment, it is almost impossible to fully expand the lung via decortication and therefore a possible residual pleural space which can cause repeated infection. Under this circumstance, a thorough decortication is not practical because tumor cells are prone to bleed and cause the underneath lung tissue to be more fragile. Too much "peeling" will lead to excessive bleeding resulting in hematoma retention and causing the lung to tear. To weigh the benefits and risks of surgical intervention is crucial since the patient's life expectancy may

be limited. From the author's personal experience, debridement, irrigation, and limited decortication followed by a tube thoracostomy are sufficient to treat the infected pleural cavity.

#### **5.4 Tuberculous empyema**

Although some surgical measures for chronic empyema originated from treating tuberculous (TB) empyema [8, 29], such as Eloesser flap thoracostomy window and thoracoplasty, these intensive procedures are now rarely used to treat TB empyema. It is not that TB empyema patients do not need invasive procedures, but it is that most of these patients can be managed by tube thoracostomy or VATS debridement with decortication. When it comes to uncontrolled TB empyema with initial treatment attempt failure, more aggressive modalities should be considered which are the same as treating other bacterial chronic empyema.

#### **5.5 Application of double lumen endotracheal tube**

Double lumen endotracheal tube intubation is frequently seen in thoracic surgery for lung isolation. It can be an adjunct to help with BPF treatment after pneumonectomy if the patient still requires ventilator support or to protect the remaining lung from fistular spillage. Application of this device would help ventilate the remaining side of the lung and leave the fistular side of the hemithorax unventilated to accelerate fistular healing. However, the diameter of the double lumen tube is certainly greater than the single lumen tube which would make the patient feel uncomfortable if not sedated. Another frequently encountered issue is that the left-sided tube tip would slide outward easily, and this malposition may cause failure of lung isolation. Although the whole diameter of the double lumen is greater than the single lumen tube, each individual double lumen tube diameter is smaller. This would make it difficult to clean the airway by suction as the suction tip may not always reach to the proper depth. As a result, airway hygiene may become a serious issue if the tube is placed in the bronchus for a long time.

#### **6. Future directions**

With the development of modern medicine and minimally invasive technology, the role of both bronchoscopic and thoracoscopic (VATS) procedures have become increasingly important replacing some of the traditional surgeries in treating chronic empyema. More studies should focus on solving existing issues like, Mini-VAC replacing OWT completely, customized device to help repairing BPF, and 3D bioprinting assisting BPF closure. The author believes that chronic empyema management is still evolving, and look forward to less traumatic ways of approach with better outcome in the future.

#### **7. Conclusions**

Treating chronic empyema and BPF are certainly clinical challenges that thoracic surgeons would encounter from time to time. It is necessary to thoroughly comprehend each treatment option and some management key points of different situations. With the development of modern technology, more treatment modalities can be anticipated.

#### **Notes/Thanks/Other declarations**

The author has nothing to declare.

#### **Author details**

Yu-Hui Yang MacKay Memorial Hospital, Taipei, Taiwan

\*Address all correspondence to: b101090099@tmu.edu.tw

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Surgical Challenges of Chronic Empyema and Bronchopleural Fistula DOI: http://dx.doi.org/10.5772/intechopen.100313*

#### **References**

[1] Light RW, Girard WM, Jenkinson SG, George RB. Parapneumonic effusions. The American journal of medicine. 1980 Oct 1;69(4):507-512.

[2] Solaini L, Prusciano F, Bagioni P. Video-assisted thoracic surgery in the treatment of pleural empyema. Surgical endoscopy. 2007 Feb;21(2):280-284.

[3] Taylor MD, Kozower BD. Surgical spectrum in the management of empyemas. Thoracic surgery clinics. 2012 Aug 1;22(3):431-440.

[4] Andrews NC. Management of nontuberculous empyema: a statement of the subcommittee on surgery. Am Rev Respir Dis. 1962;85:935.

[5] Wozniak CJ, Paull DE, Moezzi JE, Scott RP, Anstadt MP, York VV, Little AG. Choice of first intervention is related to outcomes in the management of empyema. The Annals of thoracic surgery. 2009 May 1;87(5):1525-1531.

[6] Semenkovich TR, Olsen MA, Puri V, Meyers BF, Kozower BD. Current state of empyema management. The Annals of thoracic surgery. 2018 Jun 1;105(6): 1589-1596.

[7] Chambers A, Routledge T, Dunning J, Scarci M. Is video-assisted thoracoscopic surgical decortication superior to open surgery in the management of adults with primary empyema?. Interactive cardiovascular and thoracic surgery. 2010 Aug 1;11(2):171-177.

[8] Eloesser L. An operation for tuberculous empyema. Diseases of the Chest. 1935 Oct 1;1(8):23.

[9] Symbas PN, Nugent JT, Abbott OA, Logan Jr WD, Hatcher Jr CR. Nontuberculous pleural empyema in adults: the role of a modified Eloesser procedure in its management. The

Annals of thoracic surgery. 1971 Jul 1;12(1):69-78.

[10] Thourani VH, Lancaster RT, Mansour KA, Miller Jr JI. Twenty-six years of experience with the modified Eloesser flap. The Annals of thoracic surgery. 2003 Aug 1;76(2):401-406.

[11] Denlinger CE. Eloesser flap thoracostomy window. Operative Techniques in Thoracic and Cardiovascular Surgery. 2010 Mar 1;15(1):61-69.

[12] Massera F, Robustellini M, Della Pona C, Rossi G, Rizzi A, Rocco G. Predictors of successful closure of open window thoracostomy for postpneumonectomy empyema. The Annals of thoracic surgery. 2006 Jul 1;82(1):288-292.

[13] Saadi A, Perentes JY, Gonzalez M, Tempia AC, Wang Y, Demartines N, Ris HB, Krueger T. Vacuum-assisted closure device: a useful tool in the management of severe intrathoracic infections. The Annals of thoracic surgery. 2011 May 1;91(5):1582-1589.

[14] Varker KA, Ng T. Management of empyema cavity with the vacuumassisted closure device. The Annals of thoracic surgery. 2006 Feb 1;81(2): 723-725.

[15] Haghshenasskashani A, Rahnavardi M, Yan TD, McCaughan BC. Intrathoracic application of a vacuumassisted closure device in managing pleural space infection after lung resection: is it an option?. Interactive cardiovascular and thoracic surgery. 2011 Aug 1;13(2):168-174.

[16] Perentes JY, Abdelnour-Berchtold E, Blatter J, Lovis A, Ris HB, Krueger T, Gonzalez M. Vacuum-assisted closure device for the management of infected postpneumonectomy chest cavities. The

Journal of thoracic and cardiovascular surgery. 2015 Mar 1;149(3):745-750.

[17] Sziklavari Z, Grosser C, Neu R, Schemm R, Kortner A, Szöke T, Hofmann HS. Complex pleural empyema can be safely treated with vacuum-assisted closure. Journal of cardiothoracic surgery. 2011 Dec;6(1): 1-6.

[18] Aru GM, Jew NB, Tribble CG, Merrill WH. Intrathoracic vacuumassisted management of persistent and infected pleural spaces. The Annals of thoracic surgery. 2010 Jul 1;90(1):266-270.

[19] Palmen M, van Breugel HN, Geskes GG, van Belle A, Swennen JM, Drijkoningen AH, van der Hulst RR, Maessen JG. Open window thoracostomy treatment of empyema is accelerated by vacuum-assisted closure. The Annals of thoracic surgery. 2009 Oct 1;88(4):1131-1136.

[20] Sziklavari Z, Grosser C, Neu R, Schemm R, Szöke T, Ried M, Hofmann HS. Minimally invasive vacuum-assisted closure therapy in the management of complex pleural empyema. Interactive cardiovascular and thoracic surgery. 2013 Jul 1;17(1):49-53.

[21] Yang YH, Mok LM, Tai HC. A Novel Therapeutic Approach Using the Combination of Vacuum-assisted Closure System and 1-Way Valve After Open-Window Thoracostomy in Treating Chronic Empyema Complicated by Multiple Bronchopleural Fistulae. Clinical Pulmonary Medicine. 2019 May 1;26(3):82-86.

[22] Clagett OT, Geraci JE. A procedure for the management of postpneumonectomy empyema. The Journal of thoracic and cardiovascular surgery. 1963 Feb 1;45(2):141-145.

[23] Gharagozloo F, Trachiotis G, Wolfe A, DuBree KJ, Cox JL. Pleural space irrigation and modified Clagett procedure for the treatment of early postpneumonectomy empyema. The Journal of thoracic and cardiovascular surgery. 1998 Dec 1;116(6):943-948.

[24] Zahid I, Routledge T, Billè A, Scarci M. What is the best treatment of postpneumonectomy empyema?. Interactive cardiovascular and thoracic surgery. 2011 Feb 1;12(2):260-264.

[25] Zaheer S, Allen MS, Cassivi SD, Nichols III FC, Johnson CH, Deschamps C, Pairolero PC. Postpneumonectomy empyema: results after the Clagett procedure. The Annals of thoracic surgery. 2006 Jul 1;82(1): 279-287.

[26] Schneiter D, Grodzki T, Lardinois D, Kestenholz PB, Wojcik J, Kubisa B, Pierog J, Weder W. Accelerated treatment of postpneumonectomy empyema: a binational long-term study. The Journal of thoracic and cardiovascular surgery. 2008 Jul 1;136(1):179-185.

[27] Takanari K, Kamei Y, Toriyama K, Yagi S, Torii S. Management of postpneumonectomy empyema using free flap and pedicled flap. The Annals of thoracic surgery. 2010 Jan 1;89(1):321-323.

[28] Okumura Y, Takeda SI, Asada H, Inoue M, Sawabata N, Shiono H, Maeda H. Surgical results for chronic empyema using omental pedicled flap: long-term follow-up study. The Annals of thoracic surgery. 2005 Jun 1;79(6):1857-1861.

[29] Estlander JA. Résection des côtes dans l'empyème chronique. Rev Med Chir (Paris). 1879;3:157-70.

[30] Bribriesco A, Patterson GA. Management of postpneumonectomy bronchopleural fistula: from

#### *Surgical Challenges of Chronic Empyema and Bronchopleural Fistula DOI: http://dx.doi.org/10.5772/intechopen.100313*

thoracoplasty to transsternal closure. Thoracic surgery clinics. 2018 Aug 1;28(3):323-335.

[31] Lewis CW, Wolfe WG. Thoracoplasty in the new millennium. Operative Techniques in Thoracic and Cardiovascular Surgery. 2000 May 1;5(2):135-143.

[32] Botianu PV, Botianu AM. Thoracomyoplasty in the treatment of empyema: current indications, basic principles, and results. Pulmonary medicine. 2012 May 14;2012.

[33] Krassas A, Grima R, Bagan P, Badia A, Arame A, Barthes FL, Riquet M. Current indications and results for thoracoplasty and intrathoracic muscle transposition. European Journal of Cardio-thoracic Surgery. 2010 May 1;37(5):1215-1220.

[34] Mazzella A, Pardolesi A, Maisonneuve P, Petrella F, Galetta D, Gasparri R, Spaggiari L. Bronchopleural fistula after pneumonectomy: risk factors and management, focusing on open-window thoracostomy. InSeminars in thoracic and cardiovascular surgery 2018 Mar 1 (Vol. 30, No. 1, pp. 104-113). WB Saunders.

[35] Hollaus PH, Lax F, Janakiev D, Lucciarini P, Katz E, Kreuzer A, Pridun NS. Endoscopic treatment of postoperative bronchopleural fistula: experience with 45 cases. The Annals of thoracic surgery. 1998 Sep 1;66(3): 923-927.

[36] Machida Y, Tanaka M, Motono N, Maeda S, Usuda K, Sagawa M. Successful treatment of bronchial fistula after pulmonary lobectomy by endobronchial embolization using an endobronchial watanabe spigot. Case reports in pulmonology. 2015 Apr 15;2015.

[37] Dalar L, Kosar F, Eryuksel E, Karasulu L, Altin S. Endobronchial Watanabe spigot embolisation in the treatment of bronchopleural fistula due to tuberculous empyema in intensive care unit. Annals of Thoracic and Cardiovascular Surgery. 2012 Jun 25:cr-11.

[38] Yang L, Kong J, Tao W, Song Y, Huang T, He F, Zhang P, Cai X, Dou Y, Wang Z. Tuberculosis bronchopleural fistula treated with atrial septal defect occluder. The Annals of thoracic surgery. 2013 Jul 1;96(1):e9-11.
