Methods: Between January 2005 and May 2018, a total of 152 patients (135 males, 17 females; mean age: 61.9±7.5 years; range, 45 to 73 years) who underwent right lower lobectomy for non-small cell lung cancer were retrospectively analyzed. Data including age, sex, preoperative white blood cell count and lymphocyte/monocyte ratio, smoking, preexisting chronic diseases, body mass index, stage of lung cancer, the use of neoadjuvant chemotherapy, type of surgery, operation duration, blood transfusion, and postoperative intensive care unit admission were recorded.
Results: Twenty-five (16.4%) patients developed postoperative pneumonia. Older patients presenting with elevated levels of preoperative white blood cell count and lymphocyte/monocyte ratio, excessive tobacco consumption, prolonged operation duration, history of a chronic disease, a body mass index over 30 kg/m2, advanced lung cancer, neoadjuvant chemotherapy, and intensive care unit admission after surgery were at high risk for postoperative pneumonia. There was no significant difference in sex, type of surgery (thoracotomy versus thoracoscopy), and the use of blood products. In predicting the development of postoperative pneumonia, lymphocyte/monocyte ratio had 85.% sensitivity and 87.5% specificity, while white blood cell count had 72.5% sensitivity and 77.5% specificity.
Conclusion: Preoperative white blood cell count and lymphocyte/ monocyte ratio provide supporting evidence in predicting pneumonia following lobectomy contributing to the existing risk identification criteria.
Infections succeeding major surgeries constitute up to 16% of all nosocomial infections.[1] Pneumonia is a significant concern with an incidence as high as 6% following lobectomy.[2,3] Development of atelectasis and sputum retention frequently progress to pneumonia, whereas age, smoking, preexisting chronic diseases, impaired respiratory function, and surgical techniques are among the major risk factors.[1-3]
Postoperative pneumonia (POP), almost tripling the mortality rate of lobectomy for lung cancer in the early postoperative period, necessitates rapid and appropriate treatment modalities. Patients who are candidates for lung resection should be cautiously evaluated preoperatively to identify the potential risks.
In this study, we aimed to investigate a vast of number of factors associated with the development of POP following lobectomy and to investigate, for the first time, unprecedented entities including preoperative white blood cell count (WBC) and lymphocyte/ monocyte ratio (LMR).
A detailed physical examination, complete blood count analysis, and necessary consultations from related departments were performed preoperatively. All patients were assessed with a pulmonary function test, and a contrast-enhanced computed tomography on the last day before surgery. For antibiotic prophylaxis, a single 1 g dose of first-generation cephalosporin was administrated intravenously at the time of anesthesia induction. Lobectomies were carried out via lateral thoracotomy and three-port thoracoscopy was performed by the same team consisting of three surgeons having similar experience in resections to prevent the variations of surgical techniques and operator experience. The early postoperative follow-up was carried out in the ward or in the intensive care unit (ICU) for the assessment of general health status after surgery. Routine analgesia was ordered including paracetamol (1 g three times a day intravenously or 500 mg four times a day per oral) and tramadol hydrochloride (100 mg twice a day). A chest X-ray and complete blood count analysis were performed daily beginning at the first postoperative day. Figure 1 demonstrates individual examples of radiological appearance of POP in four different cases.
Figure 1: Images of post-lobectomy pneumonia on chest (a) X-ray and (b) computed chest tomography.
Postoperative pneumonia was accepted as the presence of new or progressive pulmonary infiltrates on radiological examinations occurring within 30 days after lobectomy accompanied by fever over 38ºC, a WBC count exceeding 11,000/?L, and purulent sputum or isolation of pathogens in respiratory secretions. Microbial cultures were collected by sputum sampling or bronchoscopic lavage or both. Severity of pneumonia and response to antibiotic treatment were synchronously checked by examining levels of serum C-reactive protein and procalcitonin. The patients who developed pneumonia after discharge were admitted to hospital or prescribed with oral antibiotics following the recommendations of Infectious Diseases Department.
Data collection
For each patient, data including age, sex,
preoperative WBC and LMR, smoking history
within the past 30 days, and pack year of smoking
were recorded. The WBC and LMR were measured
via complete blood count analysis obtained within
the past 24 h before surgery. Available preexisting
chronic diseases were noted as diabetes mellitus
(DM), chronic obstructive pulmonary disease (COPD),
and cardiovascular disease (CVD). Lung cancer was
staged according to the eighth edition of Tumor,
Node, Metastasis (TNM) classification depending on
the pathology reports. The presence of neoadjuvant
chemotherapy was confirmed by reviewing the patient files. Type of surgery was recorded as thoracotomy
or video-assisted thoracic surgery (VATS), while a
thoracoscopy converted to open surgery was regarded
as thoracotomy. Operation duration was calculated as
the interval between anesthesia induction and closure
of the incision. Single-unit transfusion of packed red
blood cells administered during or after surgery and
postoperative ICU admission were also recorded.
Regarding the development of POP, all patients were
further divided into two subgroups to achieve a
comparative analysis.
Statistical analysis
Statistical analysis was performed using the SPSS
for Windows version 24.0 software (IBM Corp.,
Armonk, NY, USA). Continuous variables were
expressed in mean ± standard deviation (SD), median
(min-max), while categorical variables were expressed
in number and percentage. After checking that the data
were normally distributed using the Shapiro-Wilk and
Skewness-Kurtosis tests, parametric tests were applied.
The independent t-test was used to compare the mean
value of measurements for patient groups and the chi-square test was used to examine the relationship
between categorical variables. The receiver operating
characteristic (ROC) curve analysis was performed
and sensitivity and specificity were calculated. A p
value of <0.05 was considered statistically significant.
Table 1: Demographic and clinical characteristics of patients
The mean age was 70.3 years and 60.3 years for the POP and non-POP groups, respectively. The mean preoperative WBC was 9,244/?L and LMR was 2.22 where both parameters were higher in patients who developed POP. The increased amount of smoking (mean=25.0 vs. 10.1 pack years, respectively) and prolonged operation time (mean=111.2 vs. 89.1 min, respectively) were observed in favor of the cases who developed POP. Considering the status of POP, no significant difference was found in terms of sex, while the majority of the patients in both groups were already males. The rate of POP was higher among the patients who continued smoking (n=23), who had a preexisting chronic disease (n=24) or a BMI >30 kg/m2 (n=20).
In addition, POP was more frequent with advanced lung cancer and the most common Stage was IIb in the patients with POP (n=16, 64%). Neoadjuvant therapy also appeared as a significant risk factor and 20 of 35 patients who received neoadjuvant therapy developed POP. Seventeen (11.2%) patients who were admitted to the ICU in the late postoperative period were in the POP-developing group. The rate of POP did not indicate a significant difference in terms of the type of surgery as open thoracotomy versus VATS. The number of the patients who underwent these operations and developed POP were 18 and seven, respectively. The blood transfusion rates were 38.5% and 21.3% for the POP and non-POP groups.
Elder patients with elevated levels of preoperative WBC and LMR, excessive tobacco consumption and longer period during surgery were more predisposed to develop pneumonia. The prevalence of pneumonia was also higher in patients who continued smoking, having a history of a chronic disease, a BMI of >30 kg/m2, who developed advanced lung cancer, underwent neoadjuvant chemotherapy, and received treatment in the ICU after surgery (p<0.05). However, the rate of POP was not significantly different between the groups in terms of sex, type of surgery, and administration of blood transfusion (p>0.05) (Table 2).
Table 2: Comparison of patients regarding the development of postoperative pneumonia
The ROC analysis demonstrated that LMR yielded 85% sensitivity and 87.5% specificity (area under the curve [AUC]: 0.938) for a cut-off value of 1.75, whereas WBC showed 72.5% sensitivity and 77.5% specificity (AUC: 0.813) with a cut-off value of 8,500/?L in predicting a potential POP (Figure 2).
Among 25 patients who had developed POP, 16 (64%) were admitted to the ICU where they spent a mean length of 6.2 (range, 3 to 16) days and then recovered. Eight (32%) patients who developed empyema underwent a further surgical procedure, and three (12%) of them deceased due to sepsis and multiorgan failure.
Morbidity of postoperative infections following major thoracic surgery is a significant concern with an incidence ranging between 11 and 46%.[2-4] Postoperative pneumonia alone develops at rates as high as 6%, increasing the mortality, ICU admission and length of hospital stay, thereby, causing a six-month reduction in the mean overall survival after lobectomy.[5-7] The rate of POP was 16.4% in this series which demonstrated significant amplitude compared to the expected scale. Distinction of our clinic as a reference address for the patients who pose a risk for potentially more advanced surgeries might have induced this outcome.
The most commonly known patient-related risk factors for the development of POP were previously reported as age, deteriorated respiratory function, DM, advanced cancer, smoking, neoadjuvant chemotherapy, whereas inadequate antibiotic prophylaxis, duration of surgery, massive blood transfusion and thoracotomy were reported as surgery-related risk factors.[8-13] Consistent with the findings of recent studies, this study also confirmed that development of POP was structurally related to older age, current smoking status and amount of consumed tobacco, advanced lung cancer, neoadjuvant chemotherapy, longer duration of surgery, and preexisting chronic diseases, particularly DM and COPD. Moreover, the patients with a BMI exceeding 30 kg/m2 who were to prone to have chronic diseases more frequently and who needed ICU admission following lobectomy due to ventilatory impairment were at a significant risk for POP. Considering high BMI and requirement of postoperative ICU stay as unmentioned risk factors for POP may contribute to the current literature.
Regarding its infrequent complications and more comfortable technique for the patients, VATS has been advocated to be less involved in the development of POP, compared to open thoracotomy.[6,9,10] However, VATS still does not comply with some of pulmonary resections and also brings its own disadvantages, including requirement of experience and specific surgical instruments, prolonged operation duration, and increased cost. In our study, statistical analysis demonstrated that VATS did not provide any convenience in reducing the risk of POP.
Quantifying the amount of transfusion is also essential to estimate the severity of blood loss during surgery which may result from pneumonia due to surgical complications, prolonged operation duration, and need of postoperative ICU admission. Some recent studies have indicated blood transfusion as a potential cause for the development of POP, mostly without considering these issues.[11,13,14] The findings of this study failed to indicate single-unit of blood transfusion as a risk for post-lobectomy pneumonia.
Furthermore, recent studies have supported the LMR as a good predictor in any inflammatory events, as well as malignancies.[15,16] Low levels of LMR have been shown to be negative prognostic markers in colon cancer, whereas elevated preoperative LMR has been independently associated with poor long-term survival in patients with hepatocellular carcinoma.[15,16] Unfortunately, the literature does not include any data concerning the relation between LMR and development of POP. In this study, for the first time, a preoperative LMR of >1.75 and serum WBC exceeding 8,500/?L were found to be significant risk factors for POP.
Prevention strategy for POP initially depends on identifying the patients who are more frequently predisposed to develop this complication. Other measures which must be taken include smoking cessation within four weeks before surgery, postoperative chest physiotherapy, inhaled mucolytics, pain control, and removal of chest tubes as soon as possible.[17-20] In addition, current guidelines still approve a single dose of prophylactic antibiotics prior to surgery.[10,13,16] The presence of preoperative risk factors may not certify the development of pneumonia, thus, does not necessitate enhanced administration of antibiotics in the pre- or postoperative periods. However, recognizing the high-risk patients before surgery may help the surgeons to be alerted for potential pneumonia.
The main limitations of this study are the retrospective design and the lack of comparative data discriminating histological types of lung cancer and including all types of lobectomies to improve the conclusion. However, the main strength of this study is that two new parameters were, for the first time, investigated in addition to the absolute inclusion of recently examined risk factors.
In conclusion, postoperative pneumonia impairs the outcomes of surgery for primary lung cancer. The prevention strategy mainly involves intensive assessment to identify high-risk patients prior to pulmonary resections. In addition to already known risk factors, preoperative white blood cell count and lymphocyte/monocyte ratio indicate a valuable support to predict an oncoming pneumonia and may help surgeons to select accurate candidates for surgery and take a broader scale of precautions.
Declaration of conflicting interests
The author declared no conflicts of interest with respect to
the authorship and/or publication of this article.
Funding
The author received no financial support for the research
and/or authorship of this article.
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