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Eur J Cardiothorac Surg 1999;16:276-282
© 1999 Elsevier Science NL

Local control of disease and survival following bronchoplastic lobectomy for non-small cell lung cancer

Service de Chirurgie Thoracique and Institut de Pathologie, Hôpitaux Universitaires de Strasbourg, F-67091 Strasbourg, France

Corresponding author. Tel.: +33-3-88-11-62-02; fax: +33-3-88-11-60-77
e-mail: Gilbert.Massard{at}chru-strasbourg.fr

	Abstract

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Comments References

 
Background: This study was designed to determine whether bronchoplastic resection could be an alternative to pneumonectomy in patients with operable primary lung cancer. Methods: From 1980 to 1996, 63 patients (59 males and four females; mean age 62±7 years) underwent a bronchoplastic lobectomy for non-small cell lung cancer, indicated because of a disabled respiratory function in 34 patients, and performed electively in 29 patients. There were 38 right upper lobectomies, four bilobectomies, one middle lobectomy combined with lower lobe apical segmentectomy, ten left upper and ten left lower lobectomies. The bronchoplasty was a full sleeve in 24 patients, and a bronchial wedge resection in 39. Results: A single patient died post-operatively (1.6%). Specific procedure-related complications are summarized as follows: six anastomotic complications managed conservatively (9.5%), 15 space problems (23.8%), nine sputum retentions (14.2%). Pathologic staging classified 30 patients in stage I, 21 patients in stage II, and 12 in stage IIIA. Estimated 5-year survival was 69.7±9.8% in stage I, 37.1±12.1% in stage II, and 8.3±8.0% in stage IIIA. Fourteen patients (22.2%) developed locoregional recurrence. Three of them died with local recurrence alone, whereas 10 developed metastatic progression; a single patient is alive following completion pneumonectomy. According to stage, three recurrences occurred in stage I (10%), six in stage II (28%), and five in stage IIIA (38%). Actuarial freedom from local recurrence was significantly higher after elective procedures (P=0.019); there was a trend towards improved outcome following right-sided procedures (P=0.079) and following wedge bronchoplasty (P=0.055). Five patients experienced a second primary cancer (7.9%), which was resected in four. Conclusion: Bronchoplastic resections achieve local control and long-term survival comparable to standard resections in patients with stage I or II disease, and may be considered as a valuable alternative to pneumonectomy.

Key Words: Lung cancer • Sleeve lobectomy • Bronchoplasty • Survival • Recurrence

	1. Introduction

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Comments References

 
Curative resection for primary bronchogenic cancer usually relies on anatomic resection of the concerned pulmonary lobe or whole lung, performed together with a radical dissection of the ipsilateral mediastinal lymph nodes [1]. Therefore, tumors involving the vicinity of the right upper lobe takeoff, or takeoff of either lobe on the left side, have most often been managed with pneumonectomy. The so-called bronchoplastic lobectomies are defined as resections extended to the main bronchus, and followed by reimplantation of the remaining lobar bronchus into the stem bronchus. Such procedures have initially been designed for patients who would not tolerate pneumonectomy for functional reasons. Even today, such operations are regarded upon as a less radical compromise, subjected to an increased rate of local recurrence [2]. However, some pioneering teams have advocated bronchoplastic lobectomies as an alternative to pneumonectomy in selected cases of patients with normal lung function [3,4]. Parenchyma sparing resections have at least three potential advantages. Post-operatively, mortality and morbidity should be lowered, given that the deleterious and procedure-specific complications of pneumonectomy such as bronchopleural fistula and post-resection pulmonary edema are avoided. The mortality of lobectomy is usually less than 2%, whereas the mortality of pneumonectomy may exceed 6%. [5]. Quality of life is obviously dependent on post-resectional respiratory function [6]. Lung-saving resection further allows for radical resection of second primary lung cancer. In patients with stage I disease, incidence of second primary cancer may reach 11.4% [7]. The feasibility of surgery on the residual lung after pneumonectomy has been demonstrated by several case reports; however, these rare patients are carefully selected, and formal lobectomy is exceptionally possible [8]. On the other hand, bronchoplastic lobectomy may be followed by contralateral lobectomy or completion pneumonectomy, with fair expectations for long term survival [9].

A previous publication by our group has stressed an increased risk for local recurrence following bronchoplastic lobectomies, when compared to a paired sample of patients with pneumonectomy [2]. However, the latter study did not analyse the impact of the stage of disease. The purpose of the present study was to reassess the operative risk and long-term result on cancer control over a more recent time span.

	2. Patients and methods

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Comments References

 
2.1. Patients
From 1980 to 1996, 63 patients underwent a bronchoplastic lobectomy for primary non-small cell lung cancer. These were 59 males and four females, with a mean age of 62±7 years (range, 40–81 years). The precise tissue diagnosis was squamous cell carcinoma in 57 patients, adenocarcinoma in four, adenosquamous carcinoma in one, and large cell carcinoma in one. In 34 patients, bronchoplastic lobectomy was indicated because respiratory function precluded pneumonectomy: 28 had severe chronic obstructive pulmonary disease, four had multiple primary cancer, and two required bronchoplasty for technical problems during closure of the bronchial stump following initial standard lobectomy. An elective use of bronchoplasty was made in 29 patients with subnormal lung function, who would otherwise have tolerated a pneumonectomy. A full sleeve resection was performed in 24 patients, and a bronchial wedge excision was performed in 39. The choice for either procedure was made intraoperatively, according to endoscopic data and intraoperative findings. There were 38 right upper lobectomies, four bilobectomies, one combined resection of the right middle lobe and apical segment of the right lower lobe, ten left upper lobectomies and ten left lower lobectomies (Table 1).

2.3. Methods
Operative risk was expressed in terms of mortality and morbidity. Mortality was defined as any death occurring during the first 30 days, or during the initial hospital stay. Morbidity was allocated to three groups: procedure-specific complications of bronchoplasty, non-specific surgical complications, and medical complications. Procedure related complications included retention of secretions determining atelectasis or pneumonia, anastomotic leaks and anastomotic strictures (>50% of the lumen). Non-specific surgical morbidity included post-operative hemorrhage, pleural space disease such as prolonged air leaks (>7 days) or secondary pneumothorax. Medical complications included any non-surgical event which either prolonged the planned hospital stay, or required a modification of the standard post-operative management pathway.

Patients’ survival data were completed for 1 August 1997. Details regarding cause of death, and loco-regional status were accrued. Classification into stages was made along the 1997 guidelines.

2.4. Statistics
Qualitative data were compared with the chi-square test. Survival estimates were made with the Kaplan–Meier model, and compared with the log-rank test.

Actuarial freedom from local recurrence was calculated according to the Kaplan–Meier model, with local recurrence being considered as event. Statistical signification was admitted for any value of P less than 0.05.

	3. Results

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Comments References

 
3.1. Operative risk
A single patient died post-operatively owing to diffuse pneumonia (1.6%).

Anastomotic complications were observed in six patients (9.5%); these were four partial dehiscences (6.3%), and two anastomotic strictures (3.2%). None of them required reoperative management. Nine patients experienced significant retention of secretions (14.3%): seven developed atelectasis requiring suction-clearance with fiberoptic bronchoscopy (11.1%), and two developed pneumonia (3.2%). A single patient with a history of buccopharyngectomy, who was considered at high risk for aspiration pneumonia, was managed with immediate post-operative tracheostomy on a routine basis [11]. Prolonged air leaks were observed in 11 patients (17.4%); eight of them had undergone right upper lobectomy. Five patients having undergone right upper lobectomy experienced partial pneumothorax following withdrawal of the chest tubes (7.9%). Medical complications included two episodes of supraventricular tachycardia, one stroke, and two episodes of deep venous thrombosis followed by one pulmonary embolism.

3.2. Long-term survival
At the conclusion of the study, 27 patients were alive (43%). Three of them had been reoperated successfully meanwhile by completion pneumonectomy for a second primary cancer in two, and locoregional recurrence in one patient. Two other patients had been treated for a pharyngolaryngeal malignancy and were in complete remission.

The remaining 36 patients (57%) were deceased. A single death occurred post-operatively. Thirty-one patients (86%) died with disease: 15 had metastatic progression alone, three had loco-regional recurrence alone, ten developed both loco-regional recurrence and metastatic progression, and a final three developed a second primary cancer with subsequent metastatic progression. Four deaths occurred without evidence of disease.

Pathology assigned 30 patients to stage I, 21 patients to stage II, and 12 patients to stage IIIA. Estimated 5-year survival was 69.7±9.8% in stage I, 37.1±12.1% in stage II, and 8.3±8.0% in stage IIIA (Fig. 1). Median survival was 106 months in stage I, 34 months in stage II, and 21 months in stage III. Comparison of survival curves showed a significant difference (²=14.5; P=0.0007).

View larger version (17K): [in this window] [in a new window]   Fig. 1. Estimated survival according to stage (Kaplan–Meier).

Regarding pathologic staging, three recurrences occurred in stage I (10%), six in stage II (28%), and five in stage IIIA (38%). The apparent difference is significant when comparing stages I and III, and there is a trend towards significance when comparing stages I and (Table 2). Actuarial freedom of local recurrence at 5 years was 92.2±5.4% in stage I, which was significantly superior to the 53.2±14.3% in stage II and 51.9±15.7% in stage IIIA (Fig. 2a).

View larger version (17K): [in this window] [in a new window]   Fig. 2. Estimated freedom from local recurrence. a: Estimated freedom from recurrence according to stage; b: estimated freedom from local recurrence according to indication; c: estimated freedom from local recurrence according to side of resection; d: estimated freedom from local recurrence according to type of bronchoplasty.

Regarding the side of resection, 16.3% of right-sided, and 35% of left sided procedures were followed by loco-regional recurrence; there is a trend towards statistical significance, the stage distribution being similar in the two groups. This trend was confirmed, without reaching significance, when comparing actuarial freedom from recurrence, which was 80.3±7.5% at 5 years after right-sided procedures, and 50.2±15.7% after left sided (Fig. 2c).

The type of bronchoplasty, either full sleeve or bronchial wedge resection, had no significant impact on survival (Table 2), although a trend towards a significant difference was observed when comparing actuarial freedom of recurrence, which was 78.1±7.6% following wedge bronchoplasty, and 50.1±7.6% full sleeve bronchoplasty (Fig. 2d).

3.4. Multiple primary cancer
Multiple primary cancers motivated bronchoplastic resection in four patients (6.3%). Three had synchronous multiple primary cancers, and one patient had undergone contralateral lobectomy previously.

During follow-up, five patients were diagnosed with a second primary cancer (7.9%). Two of them occurred in patients with a first cancer classified into stage I (6.6%) and three in patients classified into stage II (14.3%); the prevalence is close to 10% when adding up stage I and II. Four patients underwent curative resection with contralateral lobectomy in two, and completion pneumonectomy in two.

3.5. Positive resection margin
Pathology revealed a positive resection margin in five patients (7.9%); conversion to pneumonectomy was precluded by the functional status. All five patients underwent adjuvant radiation therapy. Pathologic staging classified one patient into stage I, three patients into stage II, and one patient into stage IIIA. Four of these patients died with progressive disease: isolated loco-regional recurrence developed in one, isolated metastatic progression in two, and combined loco-regional and metastatic progression occurred in one.

	4. Comments

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Comments References

 
Obviously, the operative risk of bronchoplastic lobectomy is considerably lower when compared to pneumonectomy. The mortality rate observed following pneumonectomy ranges from 6 to 10% in the major published series [5]. This important fatality is explained by deleterious and procedure-specific complications. Post-pneumonectomy pulmonary edema is observed in 4–5% of patients subjected to pneumonectomy, and is most often lethal [12]. Bronchopleural fistula is observed in a range of 0–7% of patients, and still conveys a major mortality rate [13]. Besides, mortality following pneumonectomy is increased in the elderly patients [14,15]. Bronchoplastic resection was initially believed to be a high risk procedure, since older series quoted a mortality of close to 8% [16]. However, this important mortality rate was due to a relatively high incidence of bronchovascular fistulae, which occur exceptionally nowadays since the universal adoption of absorbable suture material. Recent work published by Mehran and colleagues relates a mortality of 2.1%, similar to the 1.8% of the present series [18]. Gaissert and colleagues underline that the 4% mortality observed following bronchoplastic resection compares favorably to the 9% observed following pneumonectomy at Massachussetts General Hospital [19]. Therefore, bronchoplastic resection appears as a reasonable alternative to pneumonectomy in terms of operative mortality. The feasibility of bronchoplastic resection should be discussed routinely in elderly patients [14].

Specific procedure-related complications of bronchoplasty include impaired anastomotic healing and retention of bronchial secretions. Anastomotic disruption and subsequent fistulization to the pulmonary artery has not been reported during the recent time frame. Incidence of anastomotic dehiscence is roughly evaluated at 3.5% [20]; reoperative management is seldom required. Anastomotic strictures respond to a dual mechanism: bronchial ischemia is obvious following sleeve bronchoplasty; in case of bronchial wedge excision, a too generous cartilaginous bridge will bulge into the lumen and cause obstruction. The overall reported incidence of stenosis ranges from 3 to 9% [20]; however, a completion pneumonectomy for intractable sputum retention is rarely indicated. Retention of secretions may be related to bronchial denervation, which has been shown to decrease mucociliary clearance and viscoelasticity of bronchial secretions [21]. Its reported incidence varies from 4 to 12% [3,16]. Eventually, the consequences of such complications on patients’ outcome are considerably less deleterious than complications of pneumonectomy.

For anatomic reasons, right upper lobectomy is the most suitable resection for bronchoplasty, and predominates in most series [3,16]. The proximal transsection of the main stem bronchus is performed at the same level as for pneumonectomy. The distal transsection of the bronchus intermedius may be pushed at some 15 mm distal to the right upper lobe take-off. On the left side, close anatomic vicinity of the lobar take-offs narrows the resection margin. Further difficulties for conservative resection arise on the left side when the uppermost branches of the left pulmonary artery are involved by the tumor. In this particular setting, we believe that pneumonectomy is preferable, when feasible, to the ‘double-sleeve’ operation including bronchoplasty and angioplasty, as popularized by Vogt-Moykopf and colleagues [10]. The latter type of resection conveys an important mortality rate, exceeding 10% in the experience of its inceptor [10].

The lower operative risk is insufficient to legitimize a particular type of operation, which would achieve a less optimal control of disease than any standard procedure. Obviously, the prevalence of microscopic involvement of the resection margin increases, when distance between gross intrabronchial tumor and resection margin decreases. Kayser and colleagues have demonstrated that less than 5% of bronchial sections are involved provided that the distance between gross tumor and bronchial transsection equals or exceeds 10 mm [22]. Following bronchoplastic lobectomies, available data estimate a prevalence of positive resection margins ranging from 6.9 to 13% [17,18]. This relatively high prevalence of R1 resections must be accepted in patients whose impaired functional status precludes a larger resection. On the other hand, in patients with normal respiratory reserve, frozen section analysis should confirm R0 resection intraoperatively; any evidence of a positive resection margin should lead to extension of the resection. In the present series, two patients out of five with R1 margin developed local recurrence despite post-operative radiation therapy.

The rough 5-year survival estimates in our series are comparable to available data in the literature. Reported 5-year survival rates following sleeve lobectomy range from 57 to 59% in stage I, and from 21 to 46% in stage II [17,18]. The broad spectrum of survival estimates in stage II is certainly due to the varying N-staging of hilar nodes [23].

The center of debate regarding long-term results of bronchoplastic procedures is the incidence of loco-regional recurrence. Local control of the disease is one of the two main goals of surgical resection for lung cancer. Therefore, local recurrence is distressing for the surgeon, because it signs obvious failure of treatment, although local recurrence alone is rarely fatal per se [24]. Less than 5% of patients included in the present series died with isolated local recurrence. However, local recurrence severely entails quality of life. Definition of candidates at risk for recurrence is important to guide the appropriate choice of surgical resection, and to restrict bronchoplasty to low risk patients when respiratory function allows for pneumonectomy.

The incidence of 10% we observed in stage I is comparable to the 16.6% reported by Mehran and colleagues [18]; in a broad series of patients treated with predominantly conventional resections for stage I disease, Martini and colleagues reported a rate of 7% [7]. The increased recurrence rate of 28% we observed in stage II is not very satisfactory per se, but remains comparable to the 23.1% reported by Mehran and colleagues [18]. Comparatively, in a series of patients treated with conventional resection, Martini and colleagues observed a recurrence rate of 21%. Interestingly, in patients with stage II squamous cell carcinoma, the recurrence rate rose to 34% [25]. As a matter of fact, squamous cell carcinoma is largely predominant in patients with centrally located tumors suitable for sleeve resections. Obviously, definition of the appropriate resection for stage II disease remains a matter of debate. Regarding stage III disease, the local recurrence rate we observed despite adjuvant radiation therapy is unacceptable. A more radical surgery would perhaps have improved local control. However, long term survival remains poor in this category of patients. The 8% 5-year survival rate is certainly due to inclusion of patients with upper mediastinal lymph node metastases, and confirms the precept that such patients are poor candidates for surgery.

The recurrence rate was significantly lower in patients with normal lung function who underwent bronchoplasty on an elective basis. Probably, these patients had relatively small tumors which led the operating surgeon to decide for a conservative resection. The trend towards a lower incidence of recurrence following right-sided procedures may be anticipated, since the largest resection margin is obtained by right-upper sleeve lobectomy.

We conclude that bronchoplastic lobectomy is a valuable alternative to pneumonectomy in selected patients, owing to a substantially lower operative mortality rate. Rough survival data according to stage are within the generally accepted range, as is incidence of local recurrence in stage I and II. The prohibitive rate of local recurrence in patients with stage III disease fails to legitimize bronchoplastic resection in this subset of patients.

	References

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Comments References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Gilbert Massard Stefano Elia Jean-Marie Wihlm Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Massard, G. Articles by Wihlm, J.-M. Search for Related Content PubMed PubMed Citation Articles by Massard, G. Articles by Wihlm, J.-M.