Discussion
We examined the incidence of cerebral infarction in relation to different lobectomy sites. We found that left upper and left lower lobectomies were risk factors for cerebral infarction occurrence, with left upper lobectomies showing the highest OR among all other types of lobectomies.
We demonstrated that left upper lobectomy for cancer is a significant risk factor for postoperative cerebral infarction using a large, real-world dataset as opposed to case-control studies of smaller populations. Similar to the findings of our study, the incidence of postoperative cerebral infarction was reported to be higher in patients undergoing left upper lobectomy in a retrospective case-control study that collected data from 1670 patients’ medical records between 2008 and 2015.11 Resection of the left upper lobe was also reported to increase the risk of cerebral infarction in a multicentre, retrospective case-control study that used data of 610 patients collected from 153 institutions of the Japanese Association for Chest Surgery between 2004 and 2013.10
We suggest one major possible mechanism underlying the occurrence of postoperative cerebral infarction after left upper lobectomy. It is thrombosis in the long pulmonary vein stump, which has been reported previously.7–9 12 13 Long pulmonary vein stumps are more likely to remain after a left upper lobectomy, which may cause thrombosis in the left atrium after lung resection, as shown using contrast-enhanced CT.7 8 13 The median length of the pulmonary vein stump after left upper lobectomy was reported to be significantly longer than that of the other pulmonary vein stumps.8 Furthermore, blood flow evaluation using intraoperative ultrasonography showing the presence of spontaneous echo contrast in the left superior pulmonary vein stump has been reported to be predictive of thrombosis that could cause arterial infarction.9 In addition, the mechanism of thrombus formation in the vein stump was explainable by Virchow’s triad (ie, blood stasis, endothelial injury and hypercoagulability).12 These reports revealed congestion and blood flow turbulence in the long pulmonary vein stump, which may contribute to cerebral infarction after a left upper lobectomy.
On the contrary, we suggest atrial fibrillation as one minor possible mechanism underlying the occurrence of postoperative cerebral infarction after left upper lobectomy. Although only one article analysing the relationship between lobectomy and atrial fibrillation was found in our search, left lobectomy (including lower lobectomy) was suggested as a risk factor for atrial fibrillation after lobectomy in a single-centre retrospective cohort study that used data of 186 patients between 2005 and 2010,3 citing vagal stimulation associated with lobectomy and cutting vagal cardiac branches during the superior mediastinal lymph node dissection. Atrial fibrillation is a well-known cause of thrombosis in the left atrium,33 and this study provides additional evidence for the frequency of postoperative cerebral infarction after lobectomy. In addition, it may be one possible reason for the high OR for left lower lobectomy in this study. However, this was not demonstrated to be a strong mechanism in the present cohort, as the post hoc analysis including postoperative atrial fibrillation showed less OR variation. This suggestion should be clarified in subsequent interventional studies.
It is important, but challenging, to establish methods to decrease the risk of postoperative cerebral infarction for patients undergoing a left upper lobectomy for lung cancer. One suggested solution is ensuring that the pulmonary vein stumps are as short as possible during the lobectomy process, because the pulmonary vein stump after left upper lobectomy remains long in many cases.7–9 12 13 Although almost all pulmonary veins are resected with linear staplers, care should be taken to move the linear stapler to the mediastinal side when the pulmonary veins are resected to ensure that the vein stumps are short. In addition, radiological examinations, especially contrast-enhanced CT in the early postoperative period, should be considered for the early detection of blood clots. The reported median postoperative period interval before the detection of thrombus is reported to be 3 months (range, 2–19 months),8 but the onset was within 24–48 hours in some cases.34 As for medication, the use of anticoagulants (ie, heparin, warfarin or other direct oral anticoagulants) should be considered in accordance with the treatment of left atrial thrombosis. Indeed, several reports have stated that starting anticoagulant therapy immediately after surgery for pulmonary vein thrombosis led to the prevention of thrombosis and elimination of thrombus.12 35 36 The dosage and duration of treatment need to be adjusted for each patient, but the length of treatment is unknown, and the risk of bleeding needs to be considered. We hope that further research will reveal a reliable method to prevent this complication.
There are inherent limitations in the present study. First, owing to the nature of the DPC system, only data during hospitalisation could be analysed, which made it difficult to track cerebral infarctions that were related to lobectomies but occurred after discharge from the hospital. Second, data that could not be entered into the DPC database (eg, laboratory data and detailed radiological findings) and preoperative treatment for comorbidities before admission (eg, surgery or other procedures for arrhythmias such as pacemaker implantation and atrial Maze procedure) were not included in this analysis. Although some of this information can be inferred to some extent from the codes that were added when abnormal values are reported, more specific content that could be used as variables by extraction methods from sources other than the DPC system would improve the overall analysis. Third, this study is an epidemiological study and has not led to specific verification of the previously mentioned causes and preventive measures. These mentions of causes and measures were only supported by case reports or small-scale case-control studies in previous reports. Thus, it is necessary to conduct further interventional research to detect certain causes and construct treatment strategies.