Prediction of pulmonary function after lobectomy

Hellenic Journal of Surgery 86

Prediction of Pulmonary Function After LobectomyN. Baltayiannis, S. Nikolouzos, D. Anagnostopoulos, N. Bolanos, A. Chatzimichalis, G. Zacharia, A. Charpidou, K.Ν. Syrigos

Hellenic Journal of Surgery (2014) 86:3, 159-165

N. Baltayiannis, D. Anagnostopoulos, N. Bolanos, A. ChatzimichalisDepartment of Thoracic Surgery, Metaxa Memorial Cancer Hospital, Piraeus, GreeceS. NikolouzosDepartment of Surgery, Corfu General Hospital, Corfu, GreeceG. ZachariaDepartment of Anesthesiology, Corfu General Clinic, Corfu, GreeceA. Charpidou, K.Ν. SyrigosOncology Unit, 3rd Department of Medicine, Athens Medical School, Sotiria Chest Diseases Hospital, Athens, Greece

Correspondent Author: S. NikolouzosDepartment of Surgery, Corfu General Hospital, Kontokali, 49100, Corfu, Greece, Tel ++302661360400, E-mail: [email protected]

Received 22 Feb 2014; Accepted 9 April 2014

RESEARCH CLINICAL STUDY

Abstract

Aim-Background: Lung cancer is the most common cause of cancer death in both men and women in our country. It has been estimated that there will be 7,000 lung cancer deaths every year in Greece. However, many patients with bronchogenic carcinoma also have coexistent obstructive lung disease. In these patients, preoperative prediction of functional status after lung resection is mandatory. The aim of our study was to determine the effect of lobectomy on postoperative spirometric lung function.

Methods: Seventy-two patients underwent spirometric pulmonary tests preoperatively, and at three and six months after surgery. The predicted postoperative forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) were calculated using the following formula suggested by Juhl and Frost.

Results: The functional percentage loss at six months for lobectomies was 7.34% for FVC and 7.72% for FEV1 respec-tively. The linear regression analysis derived from the correlation between predicted and measured FEV1 revealed the following equation: FEV1 POSTOP = 0.00211+0.896660 X FEV1 PREOP.

Conclusions: We conclude that our formula is a reliable method for predicting postoperative respiratory function of the patients with lung cancer.

Key words: Forced vital capacity; forced expiratory volume in the first second; lobectomy, lung cancer

Introduction-aim

Lung cancer is currently the most commonly diagnosed cancer as well as the leading cause of cancer death in males globally. Among females, it is the fourth most commonly diagnosed cancer and the second leading cause of cancer death. Lung cancer accounts for 13% (1.6 million) of all cases and 18% (1.4 million) of deaths in 2008 [1].

The observed variations in lung cancer rates and trends across countries or between males and females within each country largely reflect differences in the stage and degree of the tobacco epidemic. Male lung cancer death rates are

decreasing in most Western countries, including many European countries, North America, and Australia, where the tobacco epidemic peaked during the middle part of the last century. In contrast, lung cancer rates are increasing in countries such as China and several other countries in Asia and Africa, where the epidemic has been established more recently and continues to either increase or show signs of stability.

Generally, lung cancer trends among females lag behind males because females started smoking in large numbers several decades later than males. Consequently, lung cancer rates in females are rising in many countries except the United States, Canada, the United Kingdom, and Australia, where they are plateauing. Notably, the rates in Spain, France, Belgium, and the Netherlands rates are showing an increase in more recent female birth cohorts, suggesting that the lung cancer burden in females in these countries is likely continue to rise for several decades barring any major interventions [2].

Lung cancer is the most common cause of cancer death in Greece among males aged 40 years and older. Among females, lung cancer causes the most cancer deaths in those aged 60 years and older [1]. Non-small cell lung cancer (NSCLC) accounts for 80% of all newly-diagnosed lung cancers. In 2012, lung cancer was responsible for more than 7,000 deaths in Greece, though lung cancer mortality rates

160 N. Baltayiannis et al


CT scan. PET scan and/or bone scintigraphy were added if indicated by the standard evaluating procedure, stage or clinical situation. Hilar and mediastinal lymph nodes were systematically dissected during the lobectomy [8]. All patients were restaged according to the seventh edition of the TNM classification [9].

All patients underwent spirometric pulmonary func-tion tests preoperatively, and at three and six months after surgery. Pulmonary function tests were performed while the patient was at rest in a seated upright position. These tests consisted of spirometry using Cosmed FX pony spirometer (Cosmed Srl, Rome, Italy). All respiratory function tests were performed according to the American Thoracic So-ciety (ATS)/European Respiratory Society (ERS) guidelines [10,11]. Of all the recorded parameters, the following two were used for the assessment of operability: the best forced vital capacity (FVC) and the best forced expiratory volume in the first second (FEV1).

All patients underwent posterolateral thoracotomy, ana-tomical lobectomy, and mediastinal lymphnode dissection. The same team of five house thoracic surgeons performed all operations. The predicted postoperative FEV1 and FVC were calculated using the following formulas proposed by Juhl and Frost [12]:

a. Predicted postoperative FEV1 = preoperative FEV1 X [1-(SX0.0526)], where S=number of segments resected.

b. Predicted postoperative FVC = preoperative FVC X [1-(SX0.0526)], where S=number of segments resected.

Statistical Analysis

The statistical analysis was made with the use of the programme Statistica 12 for Windows 7 edition, StatSoft, Inc.2300 East 14th street Tulsa OK 74104 USA. The rela-tionships between the predicted and actual postoperative FVC and FEV1 were calculated using linear regression. The variables FVC and FEV1 before and after surgery are expressed as mean value ± standard deviation. A signifi-cant difference was predetermined as a P value <0.05. A comparative analysis of the continuous variables FVC and FEV1 was performed with unpaired t-Test.

Results

From September 2006 to December 2008, 72 patients, of whom 7 were women, underwent lobectomy at Metaxa Memorial Cancer Hospital. Lung resections were performed for lung cancer in all patients. Demographic and clinical data of the 72 patients are described in Table 1. The mean age of patients undergoing lobectomy was 62.4 years (range 30 to 80 years).

Squamous cell carcinoma was found in 41 patients (57%), adenocarcinomas in 24 (33.4 %), former broncho-alveolar carcinoma in 5 (7%), adenosquamous cell carci-

appear to have declined or reached a plateau. However, lung cancer remains highly lethal, with incidence and mortality rates generally being nearly equal [3,4].

Surgery involving resection of the lung parenchyma has been cited as the only method of curing lung cancer and other metastatic tumours in the lung [5]. Unfortunately, only 20% of lung carcinomas can be submitted to surgery due to the fact that most cases present advanced anatomical staging in the assessment, or associated comorbidities that contraindicate surgery [6].

There is increased multidisciplinary involvement in the treatment of patients with this pathology, with a view to of-fering the best treatment possible. Protocols that determine the impact of the surgical procedure on functional status and daily activities are fundamental instruments that must be routinely implemented in order to improve quality of life.

Almost 30 years ago, the concept of quality of life was first introduced into the medical field. Schipper defined that quality of life was composed of four elements, namely [7]:

1. working capability in one’s daily life2. psychological status3. ability to maintain human relations4. degree of comfort or discomfort with physical sensation

A surgical procedure, even a major resection, does not always inevitably reduce quality of life for patients with lung cancer. For example, we have experienced in our department such patients that were urgently hospitalized, some of whom had severe respiratory distress due to a tumour mass obstructing almost completely the lumen of the main bronchus. These patients underwent pulmonary resection, after which they regained normal lung function and returned to their previous activities.

In all such patients with impaired pulmonary function, preoperative prediction of functional status after lung resection is mandatory. The prediction of postoperative lung function plays a role in predicting the surgical risk, but it also has an important impact on the quality of life of patients after resection.

The aim of this study is:a. to determine the effect of lung resection on postoperative

spirometric lung function.b. to develop a method for predicting postoperative lung

function.

Method

All patients enrolled in this study were admitted to the Thoracic Surgery Department of Metaxa Memorial Cancer Hospital for diagnosis and treatment of lung cancer. Ap-proval for this study was obtained from the local institutional Ethics Board.

Standard preoperative evaluation included a detailed clinical history and physical examination, chest radiog-raphy, bronchoscopy, chest, upper abdomen and brain

Prediction of Pulmonary Function Aft er Lobectomy 161


Measurements of FEV1

The average preoperative FEV1(FEV1-PRO) for patients undergoing lobectomy was 2.20± 0.56; the average predic-tive postoperative FEV1 (FEV1-EXP) 1.71± 0.48, and the mean actual postoperative FEV1 at 3 (FEV1-3 MON) and 6 (FEV1- 6 MON) months was 1.97± 0.50 and 2.03 ± 0.52 respectively (Table 2).

Hence, FEV1 decreased slightly 3 months after surgery and improved at 6 months but failed to reach preoperative values. In the comparison with the latter, the functional percentage loss for FEV1 was 7.72% at six months after lobectomy. Linear regression analysis (Figure 1) revealed that the preoperative FEV1 and the actual postoperative FEV1 correlated well. (r= 0.99991)

The linear regression analysis derived from this cor-relation the following equation:

FEV1 postoperative = 0.00211 + 0.896660 X FEV1 preoperative

This formula predicts with high accuracy the postop-erative forced expiratory volume in the first second of the patients undergoing lobectomy for lung cancer.

Measurements of FVC

The average preoperative FVC (FVC-PRO) for the pa-tients undergoing lobectomy was 2.86± 0.75; the average predictive postoperative FVC (FVC-EXP) 2.29± 0.64, and the mean actual postoperative FVC at 3 (FVC-3 MON) and 6 (FVC- 6 MON) months was 2.56± 0.68 and 2.65 ± 0.70 respectively (Table 3).

Hence, FVC decreased three months after surgery

noma in one (1.3 %) and carcinoid tumour in one (1.3%). The restaging of patients according to the seventh edi-

tion of the TNM classification was as follows: 7 patients T1aN0M0, 13 patients T1bN0M0, 17 patients T2aN0M0, 8 patients T2bN0M0, 5 patients T3N0M0, 2 patients T1aN1M0, 4 patients T1bN1M0, 4 patients T2aN1M0, 5 patients T2aN2M0, 3 patients T2bN2M0, 3 patients T4N1M0 and one T1N2M0.

All patients were assessed by preoperative pulmonary function tests (FEV1-PRO, FVC-PRO). Predicted postopera-tive FEV1 and FVC (FEV1-EXP, FVC-EXP) was calculated using the formulas proposed by Juhl and Frost. All patients were followed up in the out-patient department at intervals of one, three and six months. Actual postoperative FEV1 and FVC at three and six months respectively after surgery (FEV1-3 MON, FVC – 3MON, FEV1- 6 MON, FVC – 6 MON) was measured by spirometry.

Table 1. Demographic and clinical data

Age (mean age/range) 62.4/30-80

Gender (male/female) 65/7

Histology

squamous cell carcinoma

adenocarcinomas

former broncho-alveolar carcinoma

adenosquamous cell carcinoma

carcinoid tumour

41

24

5

1

1

TNM staging

T1aN0M0

T1bN0M0

T2aN0M0

T2bN0M0

T3N0M0

T1aN1M0

T1bN1M0

T2aN1M0

T2aN2M0

T2bN2M0

T4N1M0

T1bN2M0

8

12

15

10

5

2

4

4

6

2

3

1

Surgical procedures

RU lobectomy

LU lobectomy

RU and M lobectomy

LL lobectomy

RL lobectomy

M lobectomy

RL and M lobectomy

18

15

11

10

8

5

5

RU: Right Upper, LU: Left Upper, M: Middle,LL: Left Lower, RL:Right Lower

Table 2. Values (in litres) of preoperative, postoperative predicted and actual postoperative forced expiratory volume in the first second, measured at 3 and 6 months after lobectomy expressed in mean values and SDs

FEV1-PRO 2.20± 0.56

FEV1-EXP 1.71± 0.48

FEV1-3 MON 1.97± 0.50

FEV1- 6 MON 2.03 ± 0.52

Table 3. Values (in litres) of preoperative, postoperative predicted and actual postoperative forced vital capacity measured at 3 and 6 months after lobectomy expressed in mean values and SDs

FVC-PRO 2.86± 0.75

FVC-EXP 2.29± 0.64

FVC-3 MON 2.56± 0.68

FVC- 6 MON 2.65 ± 0.70



and improved slightly at six months, but failed to reach preoperative values. In the comparison with the latter, the functional percentage loss for FVC in patients undergoing lobectomy was 7.34% after six months. Linear regression analysis (Figure 2) revealed that the preoperative FVC

and the actual postoperative FVC are well correlated (r= 0.99974). The linear regression analysis derived from this correlation the following equation:

FVC POSTOP = –0.0107+0.90051 X FVC PREOP.

This formula predicts with high accuracy the post-operative forced vital capacity of the patients undergoing lobectomy for lung cancer.

DiscussionSurgical resection remains the most effective treatment

for lung cancer, one of the most frequently treated malignan-cies worldwide [13,14]. Pulmonary complications after lung resection continue to be a high source of morbidity [15].

Figure 1. Linear regression analysis revealed that the actual (FEV1- 3MON) correlated well with the preoperative FEV1 (FEV1-PRO) (r= 0.99991).

Figure 2. Linear regression analysis revealed that the actual (FVC- 3MON) correlated well with the preoperative FVC (FVC-PRO) (r= 0.99974).

Prediction of Pulmonary Function Aft er Lobectomy 163


The ability to predict which patient will have the highest risk of developing complications can aid the clinician in focusing efforts to reduce morbidity and mortality.

The FEV1 obtained by spirometry is the most com-monly used test to assess suitability of lung cancer patients for surgery. Spirometry should be performed when the patient is in a clinically stable condition and receiving maximal bronchodilator therapy. The FEV1 can be ex-pressed in either absolute values or as a percentage of the predicted value.

There have been several studies looking at the minimum absolute values of FEV1 which, as a single measurement, can predict whether a patient will survive a pneumonectomy and still have a good level of quality of life. Many studies are retrospective and have small numbers of patients. A review of the literature suggests an FEV1 >1.5 L as a safe lower limit for a lobectomy [16]. In the British Thoracic Society (BTS) guidelines, data from >2,000 patients in three large historical series in the 1970s have shown that a mortality rate of <5% can be achieved if the preoperative FEV1 is >1.5

L for a lobectomy [17].The predicted postoperative FEV1 is a frequently used

criterion for defining physiologic operability [18]. Unfor-tunately, a tolerable lower limit of postoperative FEV1 is unknown and it is also unclear how accurately we can predict the actual postoperative FEV1 from its preoperative value.

Despite these limitations, a predicted postoperative FEV1 of greater than 800 ml or greater than 40% of predicted are common criteria for resectability [19].

Both nuclear perfusion scanning and simple calculation have been used to predict postoperative FEV1. Previous studies have detected that the correlation between actual and predicted postoperative FEV1 using perfusion scanning is no better than using simple calculation [20-24].

Zeiher et al have shown that simple calculation based on studies and the equation of Juhl and Frost systematically underestimated the actual postoperative FEV1 for patients undergoing lobectomy by a total 250 ml [25].

Our aim was to examine the effects of lung resection on pulmonary function and the subsequent quality of life of the patients after surgery, in a large patient population where the surgical team, surgical techniques, spirometric techniques and patient follow-up were controlled.

We propose a new prediction equation to the calcula-tion of postoperative pulmonary function, which would more accurately predict the postoperative FEV1 of patients undergoing lobectomy

FEV1 POSTOP = 0.00211+0.896660 X FEV1 PREOP.This equation predicted with high accuracy the postop-

erative lung function of patients who underwent lobectomy for lung cancer.

Hence, we believe that by using this equation, more

patients may be candidates for potentially life-saving lung resection.

Ethical Approval

The study has been approved by ethics committee of our institutional board.

Conflict of Interest

The authors declare that there is no conflict of interest.

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ΚΛΙΝΙΚΗ ΕΡΕΥΝΑ Hellenic Journal of Surgery (2014) 86:3, 159-165

ΠΕΡΙΛΗΨΗ

Εισαγωγή - Σκοπός: Ο καρκίνος του πνεύμονα προκαλεί 7.000 θανάτους κάθε χρόνο στην Ελλάδα. Η χειρουργική επέμβαση προσφέρει την καλύτερη δυνατότητα θεραπείας των ασθενών με μη μικροκυτταρικό καρκίνο. Πρόσφατα έχει παρατηρηθεί μια αύξηση του αριθμού των περιστατικών οι οποίοι έχουν ένδειξη μείζονος πνευμονικής εκτομής λόγω πρωτοπαθούς καρκινώματος κυρίως μεταξύ ηλικιωμένων ασθενών και ασθενών με μειωμένη αναπνευστική λειτουργία. Σε αυτούς τούς ασθενείς η προεγχειρητική πρόβλεψη της κατάστασης της αναπνευστικής λειτουργίας μετά την λοβεκτομή προβάλλει επιτακτική.

Στόχος της μελέτης μας είναι να προσδιορίσει το αποτέλεσμα της λοβεκτομής στη μετεγχειρητική σπιρομέτρηση και να εκτιμήσει την ακρίβεια της απλής εξίσωσης των Juhl και Frost στην πρόβλεψη της μετεγχειρητικής αναπνευ-στικής λειτουργίας στους ασθενείς που υποβάλλονται σε λοβεκτομή.

Μέθοδος: Εβδομήντα δύο ασθενείς υποβλήθηκαν σε σπιρομετρικό έλεγχο προεγχειρητικά και 3 και 6 μήνες μετά την επέμβαση. Από όλες τις παραμέτρους που καταγράφονταν για την εκτίμηση της δυνατότητας του ασθενούς να χειρουργηθεί αλλά και για τις υπόλοιπες συγκρίσεις χρησιμοποιήθηκε ο βίαια εκπνεόμενος όγκος το πρώτο δευτερόλεπτο(FEV1). Ο προβλεπόμενος μετεγχειρητικός FEV1 υπολογίσθηκε με την εξίσωση των Juhl και Frost.

Αποτελέσματα: Σε σχέση με τις προεγχειρητικές τιμές το ποσοστό απώλειας της αναπνευστικής λειτουργίας 6 μήνες μετά την επέμβαση (μείωση του FEV1) για τούς ασθενείς που υποβλήθηκαν σε λοβεκτομή είναι 7.72%. Η γραμμική ανάλυση παλινδρόμησης ανέδειξε από την συσχέτιση μεταξύ προβλεπόμενου και μετρημένου –πραγ-ματικού FEV1 την παρακάτω εξίσωση: FEV1 POSTOP = 0.00211+0.896660 X FEV1 PREOP.

Αυτή η εξί σωση προβλέπει με μεγάλη ακρίβεια την μετεγχειρητική αναπνευστική λειτουργία των ασθενών που υποβλήθηκαν σε λοβεκτομή λόγω καρκίνου.

Συμπεράσματα: Πιστεύουμε ότι η εξίσωση μας αποτελεί μια αξιόπιστη μέθοδο πρόβλεψης της μετεγχειρητικής αναπνευστικής λειτουργίας των ασθενών που υποβάλλονται σε λοβεκτομή λόγω πρωτοπαθούς καρκίνου του πνεύμονα.

Λέξεις κλειδιά: Βίαια εκπνεόμενος όγκος το πρώτο δευτερόλεπτο, βίαιη ζωτική χωρητικότητα, λοβεκτομή, καρκίνος πνεύμονα

Πρόβλεψη αναπνευστικής λειτουργίας μετά από λοβεκτομήΝ. Μπαλταγιάννης, Σ. Νικολούζος, Δ. Αναγνωστόπουλος, Ν. Μπολάνος, Α. Χατζημιχάλης, Γ. Ζαχαρία, Α. Χαρπίδου, Κ.N. Συρίγος

Ν. Μπαλταγιάννης, Δ. Αναγνωστόπουλος, Ν. Μπολάνος, Α. ΧατζημιχάληςΘωρακοχειρουργικό Τμήμα, Αντικαρκινικό Νοσοκομείο «Μεταξά», ΠειραιάςΣ. ΝικολούζοςΧειρουργικό Τμήμα, Γενικό Νοσοκομείο Κερκύρας, ΚέρκυραΓ. ΖαχαρίαΑναισθησιολογικό Τμήμα, Γενική Κλινική Κερκύρας, ΚέρκυραΑ. Χαρπίδου, Κ.N. ΣυρίγοςΟγκολογική Μονάδα, Γ΄ Πανεπιστημιακή Παθολογική Κλινική, Ιατρική Σχολή Αθηνών, Γενικό Νοσοκομείο «Η Σωτηρία», Αθήνα

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Prediction of pulmonary function after lobectomy