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Interact CardioVasc Thorac Surg 2009;9:182-186. doi:10.1510/icvts.2009.204784 © 2009 European Association of Cardio-Thoracic Surgery
Bronchial stump infiltration after lung cancer surgery. Retrospective study of a series of 2994 patients
a H. Universitari Germans Trias i Pujol, Carretera de Canyet s/n 08916 Badalona, Barcelona, Spain Received 6 February 2009; received in revised form 16 March 2009; accepted 16 March 2009
*Corresponding author. Tel.: +34 934978921; fax: +34 934978843.
The incidence of lung cancer has been increasing in developed countries since the mid-1990s. The main objective of this study is to determine if bronquial stump infiltration can affect survival in patients with lung cancer. For this purpose, we differentiate between carcinoma ‘in situ’ and invasive carcinoma. We included patients suffering from non-small cell lung cancer who underwent thoracothomy as treatment. The total number of patients was 2994. In this study, 80 patients out of the 2994 had bronchial stump affection. Eight patients were excluded thus a total of 72 patients were included, 52 of them had carcinoma ‘in situ’ and 20 invasive carcinoma. The global survival was 25 months. Patients with carcinoma ‘in situ’ had a median survival of 25 months as opposed to 21 months in patients with invasive carcinoma. We only found statistical significance when we compared the histology with the type of bronchial stump infiltration. We did not observe statistical significance in survival between carcinoma ‘in situ’ and invasive carcinoma bronchial stump infiltration (P=0.094). The only survival predictor variable is histology (adenocarcinoma), P=0.0001.
Key Words: Lung cancer; Stump bronchial affection; Carcinoma in situ
The incidence of lung cancer has been increasing in developed countries since the mid-1990s. It is the most frequent type of cancer and it is one of the highest causes of mortality in the world and also in Spain [1]. Five-year survival in patients who have lung cancer is 15%. The low survival rate probably depends on surgery [2]. The surgery treatment objective is complete resection. Incomplete resection has no benefit to the patient and it could postpone other treatments, such as chemotherapy or radio-therapy, it could also deteriorate quality of life. The main objective of this study is to determinate if bronchial stump infiltration can affect survival in patients with lung cancer. For this purpose, we differentiate between carcinoma ‘in situ’ and invasive carcinoma. We define in situ carcinoma as an area characterized by a loss of the normal longitudinal folds of the mucosa of a bronchi that do not extend beyond the basement mem-brane. Invasive carcinoma in the bronchial stump is defined as a lesion that extends beyond the basement membrane.
All patients included in the study suffered from non-small cell lung cancer and underwent thoracotomy as treatment in hospitals belonging to the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S). We prospectively included all patients treated surgically from October 1993 to September 1997, in hospitals taking part in the GCCB-S, but the study collected this data retrospectively. This is a multidisciplinary study thus data collection was difficult and although the data was from 10 years ago the results can be used as the number of patients is high enough and we also have 10 years follow-up. The sample was complete, as verified by the inclusion in the registry of all patients undergoing surgery, including incomplete resections and exploratory thoracotomy. The total number of patients is 2994. The 1997 TNM classification was used (Table 1).
The quality of this register was assessed in the following way: the local responsible person sent patients' survival periodically. It was a first control on all the data sent and requested all doubtful or controversial data. Another control was taken by assessing the total number of thoracotomies and total number of data sent. Data from our group was also participating in IASLC. All data collected is confidential. The cumulative survival rates were calculated by the Kaplan–Meier method. The Cox proportional hazard regression model was applied by means of univariate and multivariate analysis because we are searching for a relationship with survival in our patients. A P-value <0.05 was considered statistically significant. All statistical analyses were performed with the Statistical Package for the Social Sciences (SPSS, version 11.0, Chicago, IL, USA). From the total number of the patients included in this study, 80 had bronchial stump infiltration. We excluded 8 patients (10%) because they died during the first month postoperation and would have introduced a bias in the study. Thus, included 72 patients: 52 of whom had carcinoma ‘in situ’ and 20 invasive carcinoma. All cases were diagnosed postoperatively by pathologists. We define incomplete resection (R1) as positive resection margins, extracapsular nodal involvement, unremoved positive nodes, involvement of most distant removed nodes, positive pleural effusion and pleural implants [12].
Bronchial stump affection was found in 72 patients, 52 had carcinoma ‘in situ’ (72.18%) and 20 had invasive carcinoma (27.82%). The distribution of these patients was 7 women and 65 men with an average age of 62.2 years (35–80): 38 pneumonectomies, 4 bilobectomies, 25 lobectomies and 5 patients with another type of resection that included segmental resection or a combination of the others (Table 2). We used the 1997 TNM classification.
The global survival was 25 months (16–34), CI 95%. Patients with carcinoma ‘in situ’ had a median survival of 25 months as opposed to 21 months in patients with invasive carcinoma (P=0.94) (Fig. 1).
We did not find any statistical significance comparing the histology (squamous and adenocarcinoma) with the type of bronchial stump affection (Fig. 2).
These curves compare the survival in patients with squamous cell carcinoma and adenocarcinoma with the type of surgery R0 (P=0.02) and R1 (P<0.0001) (Fig. 3). We can state that the adenocarcinoma gives worse prognosis in patients with bronchial stump affection. We did not find statistical significance in the type of infiltration of bronchial stump but we found it in the histology so we can conclude the histology is a decisive factor in survival.
Thus, we can state that the histology is not a prognostic factor in survival in lung cancer patients except in those who had incomplete surgery R1 (bronchial stump affection). We decided to study by univariant analysis the age (P=0.55), the type of surgery procedure (neumonectomy) (P=0.93), the presence or absence of lymph node affection and the histology because they seem to be the main survival factors. None of these factors except histology (adenocarcinoma) had statistical significance (P>0.0001). We observed that squamous cell carcinoma had lower risk (0.3) of death than adenocarcinoma. Although pN0 and pN1 have lower mortality risk compared with pN2, this does not have statistical significance (Table 3).
In multivariant analysis, histology is the only independent variable, thus we can state histology is a variable that can predict survival (Table 4). All the variables we have studied in multivariant analysis were independent variables in the literature and the authors have demonstrated a P-value <0.5, thus we decided to study them in our analysis.
In a second part of this study, we would like to know if the stage is an important factor, as we suppose. Because the number of patients in every stage is low it would be difficult to obtain statistical significance.
We found differences in survival in patients who had the same tumour stage, histology and surgery procedure and thus we can suppose that there are more variables that can have an influence in lung cancer survival [3]. One of these variables could be bronchial stump infiltration (R1). There are few studies on bronchial stump affection and these few studies include a small number of patients. Bronchial stump affection was described by Habein et al. in 1956. In 1975, Shields described a different type of bronchial stump affection. He described that patients with macroscopically bronchial stump infiltration had the same poor prognosis as those who had lymph node infiltration [4, 5]. Soorae and Stevenson described four different types of bronchial stump infiltration: direct tumour infiltration into bronchial wall, lymph node infiltration, peribronchial tissue infiltration and in situ carcinoma. They observed worse prognosis in all these cases [6]. Several studies show that the distance between bronchial stump and tumour is one of the most important factors. The probability of residual disease is 100% if the margin is <1 mm from the tumour, and decreases to 30% if the distance is 2–5 mm. The risk is zero when the distance is >20 mm [7]. But, the problem appears when the distance from the tumour and the macroscopically bronchial stump seems to be safe. In our study, no patients showed macroscopic disease, only microscopy infiltration. Ghiribelli et al. [8] state that in patients who have endobronchial lung cancer, we must analyse bronchial and peribronchial tissue during operation; but, these techniques have also negative impacts [3, 7, 9]. In our study, we compare survival in patients with carcinoma ‘in situ’ and patients with invasive carcinoma. The median survival is 25 months which is similar to median survival in the literature. We found 80 patients with bronchial stump affection, which represents 2.7% and is similar to the literature (1.6–14%). We excluded eight patients because they died within the first month post-surgery. Our results do not show any statistical significance between the two types of bronchial stump infiltration similar to findings of other authors, such as Kara et al. [10]. Snijder et al. [11] have showed that carcinoma ‘in situ’ has no effect on survival in patients with tumour stage I, but patients with invasive carcinoma have worse prognosis than patients with complete surgery. In univariant and multivariant analysis, we observed that the only predictive variable is histology (adenocarcinoma); this finding is also observed in other studies, such as Kara et al. [10], Liewald et al. [3], Kaiser et al. [5] and Ghiribelli et al. [8], although the last two authors did not find statistical significance. Kara et al. [10] observed that pT and pN are predictive variables in survival. We did not find this, neither did Passalick et al. [4] and Ghiribelli et al. [8]. In our study, tumour stage III represents 52.8% and this could explain why we did not find statistical significance between the two types of bronchial stump infiltration as also described by Kaiser et al. [5]. There are no standard recommendations for further treatment for patients with bronchial R1-resection. Classical options include simple observation in patients with low Karnofsky, re-operation in patients with tumour stages I and II and good cardiorespiratory conditions [3, 9] and radiotherapy in patients with pN2 affection [7]. In our study, 79% of patients were treated after surgery (24.5% tumour stage III). Massard et al. [7] observed that patients with bronchial stump infiltration have no worse prognosis than other patients and thus they recommend observation and radiotherapy in patients with peribronchial infiltration. Snijder et al. [11] observed that patients treated with radiotherapy have no better survival and they have no lower local relapse. Kaiser et al. [5] described that patients with microscopy disease treated with radiotherapy have no lower local relapse. With these results, we conclude that we must perform bronchial and peribronchial tissue biopsy.
We did not observe statistical significance in survival between carcinoma ‘in situ’ and invasive carcinoma bronchial stump infiltration (P=0.94). The only survival predictor variable is histology (adenocarcinoma), P=0.0001.
Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery Coordinators José Luis Duque, MD (Hospital Universitario, Valladolid); Ángel López Encuentra, MD (Hospital Universitario 12 de Octubre, Madrid); Ramon Rami-Porta, MD (Hospital Mútua de Terrassa, Barcelona). Local representatives Julio Astudillo, MD (Hospital Germans Trias i Pujol, Barcelona); Antonio Cantó Armengol, MD (Hospital Clínico, Valencia); Juan Casanova, MD and Manuel Mariñan, MD (Hospital de Cruces, Bilbao); Jorge Cerezal, MD (Hospital Univesitario, Valladolid); Antonio Fernández de la Rota, MD and Ricardo Arrabal, MD (Hospital Carlos Haya, Málaga); Joseph Ma Gimferrer, MD (Hospital Clínic, Barcelona); Federico González Aragoneses, MD and Nicolás Moreno Mata, MD (Hospital Gregorio Marañon, Madrid); Jorge Freixinet, MD and Pedro Rodríguez-Suárez, MD (Hospital de Gran Catania Dr. Negrín, Las Palmas); Nicolás Llobregat Poyán, MD (Hospital Central de la Defensa, Madrid); Nuria Mañez, MD (Fundación Jiménez Díaz, Madrid); Mireia Serra-Mitjans, MD (Hospital Mútua de Terrassa, Barcelona); José Luis Martín de Nicolás, MD (Hospital Universitario 12 de Octubre, Madrid); Nuria Novoa Valentín, MD (Complejo Hospitalario, Salamanca); Jesús Rodríguez, MD (Complejo Hospitalario, Oviedo); Antonio José Torres García, MD and Ana Gómez, MD (Hospital Universitario San Carlos, Madrid); Mercedes de la Torre (Hospital Juan Canalejo, La Coruña); Abel Sánchez-Palencia Ramos, MD and Javier Ruiz Zafra, MD (Hospital Virgen de las Nieves, Granada); Andrés Varela Ugarte, MD and Pablo Gámez García, MD (Clínica Puerta de Hierro, Madrid); Yat Wah Pun, MD (Hospital de la Princesa, Madrid). Data analysis Thanks to José Javier Sánchez for all his support.
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Abstract
1. Introduction
