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Evaluation of gastroesophageal reflux disease and hiatal hernia as risk factors for lobectomy complications

Open AccessPublished:June 03, 2022DOI:https://doi.org/10.1016/j.xjon.2022.05.017

      Abstract

      Objective

      Up to 40% of lobectomies are complicated by adverse events. Gastroesophageal reflux disease (GERD) and hiatal hernia have been associated with morbidity across a range of clinical scenarios, yet their relation to recovery from pulmonary resection is understudied. We evaluated GERD and hiatal hernia as predictors of complications after lobectomy for lung cancer.

      Methods

      Lobectomy patients at Yale-New Haven Hospital between January 2014 and April 2021 were evaluated for predictors of 30-day postoperative complications, pneumonia, atrial arrhythmia, readmission, and mortality. Multivariable regression models included sociodemographic characteristics, body mass index, surgical approach, cardiopulmonary comorbidities, hiatal hernia, GERD, and preoperative acid-suppressive therapy as predictors.

      Results

      Overall, 824 patients underwent lobectomy, including 50.5% with a hiatal hernia and 38.7% with GERD. The median age was 68 [interquartile range, 61-74] years, and the majority were female (58.4%). At least 1 postoperative complication developed in 39.6% of patients, including atrial arrhythmia (11.7%) and pneumonia (4.1%). Male sex (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.11-2.06, P = .01), age ≥70 years (OR, 1.55; 95% CI, 1.13-2.11, P = .01), hiatal hernia (OR, 1.40; 95% CI, 1.03-1.90, P = .03), and intraoperative packed red blood cells (OR, 4.80; 95% CI, 1.51-15.20, P = .01) were significant risk factors for developing at least 1 postoperative complication. Hiatal hernia was also a significant predictor of atrial arrhythmia (OR, 1.64; 95% CI, 1.02-2.62, P = .04) but was not associated with other adverse events.

      Conclusions

      Our findings indicate that hiatal hernia may be a novel risk factor for complications, especially atrial arrhythmia, following lobectomy that should be considered in the preoperative evaluation of lung cancer patients.

      Graphical abstract

      Key Words

      Abbreviations and Acronyms:

      BMI (body mass index), CI (confidence interval), CT (computed tomography), GERD (gastroesophageal reflux disease), OR (odds ratio), RBC (red blood cell)
      Figure thumbnail fx2
      Hiatal hernia may significantly increase the risk of postlobectomy atrial arrhythmia.
      Hiatal hernia may be a novel risk factor for complications, especially atrial arrhythmia, after lobectomy for lung cancer that should be considered during preoperative risk stratification.
      Within our single institution, hiatal hernia but not GERD was a risk factor for postoperative complications, especially atrial arrhythmia, after lobectomy. Considering hiatal hernia during preoperative risk stratification may enhance shared decision-making for pulmonary lobectomy, and if validated, potentially inform surveillance and prophylaxis strategies for atrial fibrillation in the future.
      Lung cancer can be a particularly aggressive malignancy, accounting for 158,000 cancer-related deaths each year in the United States alone.
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      Surgical management via pulmonary lobectomy has traditionally been associated with the greatest cure rates for early-stage non–small cell lung cancer, yet the complication rate (approximately 40%) is greater than for many other oncologic procedures.
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      Impact of hospital volume of thoracoscopic lobectomy on primary lung cancer outcomes.
      As a result, there is a great need to understand the risk factors for different types of surgical complications associated with lobectomy for lung cancer.
      Many factors have been associated with complication rates after lobectomy. For example, the surgical approach (thoracotomy vs minimally invasive) as well as hospital and surgeon attributes, such as annual procedural volumes, have been correlated with postoperative adverse event rates.
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      Impact of hospital volume of thoracoscopic lobectomy on primary lung cancer outcomes.
      Several patient characteristics also have been associated with lobectomy complication rates. For example, patient sex, advanced age, and tobacco smoking, all predict greater rates of complications after pulmonary resection for lung cancer.
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      Risk stratification based on patient attributes may not only improve shared decision-making and patient selection but also may expose opportunities to mitigate risk.
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      Furthermore, hiatal hernias, a common cause of GERD, can be large enough to impact cardiorespiratory function independent of GERD.
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      • et al.
      Hiatal hernia is associated with an increased prevalence of atrial fibrillation in young patients.
      Given the potential for GERD and hiatal hernia to impact respiratory and cardiac function, it is possible that these conditions could impact the recovery from pulmonary surgery to treat lung cancer. However, the relationships between GERD, hiatal hernia, and complications after surgical management for lung cancer have not been fully explored.
      We hypothesized that patients with GERD or hiatal hernia were at increased risk for complications, and specifically cardiopulmonary complications, after lobectomy for lung cancer. We examined 30-day lobectomy outcomes within our single institution experience to clarify the relationship between GERD and hiatal hernia with adverse events among patients recovering from lobectomy for lung cancer.

      Methods

      Data Source

      This study was a retrospective cohort study of patients undergoing lobectomy at Yale-New Haven Hospital. A research database was created and populated via direct chart review, as well as data-sharing from our prospectively maintained institutional database for participation in the Society of Thoracic Surgeons General Thoracic Surgery Database. The Yale School of Medicine institutional review board approved this study with consent waived because patient data were deidentified (protocol ID: 1103008160; most recent approval date March 5, 2020).

      Patient Cohort

      All patients undergoing lobectomy for lung cancer at Yale-New Haven Hospital from January 2014 to April 2021 were eligible for the study. Patients without available cross-sectional imaging (computed tomography [CT] or CT/positron emission tomography scanning) before lobectomy were excluded (13 patients, 1.6%).

      Covariates

      Covariates were determined by review of the patient's medical record and, when applicable, defined in accordance with the Society of Thoracic Surgeons General Thoracic Surgical Database.
      STS General Thoracic Surgery database data specifications version 2.41: The Society of Thoracic Surgeons.
      The following data elements were assessed: patient sex, age (<70 years old vs ≥70 years old),
      • Lee J.Y.
      • Jin S.-M.
      • Lee C.-H.
      • Lee B.-J.
      • Kang C.-H.
      • Yim J.-J.
      • et al.
      Risk factors of postoperative pneumonia after lung cancer surgery.
      race (White vs not White), body mass index (BMI; <25 vs 25-29.9 vs ≥30), lobectomy laterality (left vs right), pulmonary lobe involved (upper, middle, lower), smoking status (current smoker: yes vs no), preoperative chemotherapy within 6 months of lobectomy, previous radiation therapy, surgical approach (minimally invasive, ie, thoracoscopic or robotic-assisted, vs open), forced expiratory volume in 1 second percent of predicted (≤80% vs >80%),
      • Schussler O.
      • Alifano M.
      • Dermine H.
      • Strano S.
      • Casetta A.
      • Sepulveda S.
      • et al.
      Postoperative pneumonia after major lung resection.
      and the receipt of intraoperative red blood cells (RBCs). Information on select comorbidities was collected if documented before the day of lobectomy: asthma, previous history of pneumonia, diabetes, hypertension, coronary artery disease, hiatal hernia, and GERD. Preoperative acid-suppressive therapy was similarly determined using the electronic medical record and defined as either a proton pump inhibitor or H2-blocker. Hiatal hernia and GERD were considered independent variables, as there was imperfect overlap between the 2 diagnoses.
      Every patient had a minimum of 1 CT scan reviewed, which had to be obtained within the 6 months before operative resection and include at least a 5-mm thickness series. When available within this time frame, an additional CT scan of the chest or abdomen or a CT scan acquired in concordance with CT/positron emission tomography scan was assessed, including scans with oral contrast for other indications. Axial and coronal images with mediastinal window settings were evaluated solely for the presence of a hiatal hernia by a single radiologist (M.D.C.), without previous knowledge of diagnosis. The presence of hiatal hernia was determined by evaluation of the esophagus in relation to the diaphragm, using standard anatomical definitions (any criterion sufficient for diagnosis)
      • Dodds W.J.
      1976 Walter B. Cannon Lecture: current concepts of esophageal motor function: clinical implications for radiology.
      • Noth I.
      • Zangan S.M.
      • Soares R.V.
      • Forsythe A.
      • Demchuk C.
      • Takahashi S.M.
      • et al.
      Prevalence of hiatal hernia by blinded multidetector CT in patients with idiopathic pulmonary fibrosis.
      • Ginalski J.M.
      • Schnyder P.
      • Moss A.A.
      • Brasch R.C.
      Incidence and Significance of a Widened Esophageal Hiatus at CT Scan.
      : (1) lower esophageal ring ≥1 to 2 cm above the level of the diaphragmatic hiatus; (2) esophageal hiatus widened to 3 to 4 cm (upper limit of normal: 1.5 cm); and (3) stomach folds or oral contrast pooling above the level of the gastroesophageal junction.
      We do not routinely administer oral contrast for lung cancer screening or preoperative CT scans. However, a considerable proportion of our patients have a nodule and ultimately a cancer diagnosed as an incidental finding on a CT scan performed for an unrelated reason. A subset of these scans for unrelated reasons includes oral contrast administration.

      Outcomes

      Dependent variables included 30-day surgical complications, postoperative pneumonia, postoperative atrial arrhythmia, hospital readmission, and mortality, which were defined in accordance with the Society of Thoracic Surgeons General Thoracic Surgical Database and abstracted from the medical record by trained registrars.
      STS General Thoracic Surgery database data specifications version 2.41: The Society of Thoracic Surgeons.
      Any of the following were considered major complications: pneumonia, acute respiratory distress syndrome, bronchopleural fistula, pulmonary embolism, mechanical ventilation for >48 hours, respiratory failure, tracheostomy, myocardial infarction, and nonspecified other event requiring the operating room with anesthesia.
      • Kozower B.D.
      • O’Brien S.M.
      • Kosinski A.S.
      • Magee M.J.
      • Dokholyan R.
      • Jacobs J.P.
      • et al.
      The Society of Thoracic Surgeons composite score for rating program performance for lobectomy for lung cancer.

      Statistical Analysis

      Categorical variables were compared using the Pearson χ2 tests or the Fisher exact test, as appropriate. Multivariable logistic regression analyses were performed to identify predictors of the 30-day postoperative outcomes of interest (complications, pneumonia, atrial arrhythmia, readmission, and mortality) and were adjusted for by patient sex, age, race, BMI, tumor laterality, tumor lobe, active smoking status, preoperative chemotherapy in the 6 months before lobectomy, previous radiation therapy, surgical approach, forced expiratory volume in 1 second percentage of predicted, asthma, past pneumonia, diabetes, hypertension, coronary artery disease, hiatal hernia, GERD, preoperative acid-suppressive therapy, and intraoperative RBCs. All tests were 2-sided. Data were analyzed using SAS, version 9.4 (SAS Institute Inc) and Stata, version 16.1 (StataCorp LLC).

      Results

      Patient Population

      Overall, 824 patients underwent lobectomy, including 416 (50.5%) patients with a preoperative hiatal hernia, and 319 (38.7%) with GERD. The overlap between hiatal hernia and GERD was inconsistent, with 45.4% of hernia patients having documented GERD and 59.2% of GERD patients having a hiatal hernia. A total of 270 (32.8%) patients were documented as taking preoperative acid-suppressive therapy before lobectomy. The median age was 68 [interquartile range, 61-74] years, 481 (58.4%) patients were female, and 197 (23.9%) patients reported actively smoking at the time of lobectomy. Additional patient characteristics are listed in Table 1.
      Table 1Lobectomy patient characteristics
      Covariaten (%)
      Sex
       Female481 (58.4)
       Male343 (41.6)
      Age, y
       <70462 (56.1)
       ≥70362 (43.9)
      Race
       White711 (86.3)
       Not White113 (13.7)
      BMI
       <25276 (33.5)
       25-29.9288 (35.0)
       ≥30260 (31.5)
      Laterality
       Left310 (37.6)
       Right514 (62.4)
      Lobe
       Upper495 (60.1)
       Middle73 (8.8)
       Lower256 (31.1)
      Active smoker
       No627 (76.1)
       Yes197 (23.9)
      Preoperative chemotherapy
       No767 (93.1)
       Yes57 (6.9)
      Previous radiation therapy
       No779 (94.5)
       Yes45 (5.5)
      Minimally invasive vs open
       Minimally invasive699 (84.8)
       Open125 (15.2)
      FEV1 % predicted
       >80528 (64.1)
       ≤80273 (33.1)
       Missing23 (2.8)
      Asthma
       No673 (81.7)
       Yes151 (18.3)
      Past pneumonia
       No694 (84.2)
       Yes130 (15.8)
      Diabetes
       No685 (83.1)
       Yes139 (16.9)
      Hypertension
       No317 (38.5)
       Yes507 (61.5)
      Coronary artery disease
       No695 (84.3)
       Yes129 (15.7)
      Hiatal hernia
       No408 (49.5)
       Yes416 (50.5)
      GERD
       No505 (61.3)
       Yes319 (38.7)
      Preoperative acid-suppressive therapy
       No554 (67.2)
       Yes270 (32.8)
      Intraoperative RBCs
       No803 (97.5)
       Yes21 (2.5)
      Tumor size
       <2 cm382 (46.3)
       2-2.9 cm209 (25.4)
       3-4.9 cm162 (19.7)
       5-6.9 cm50 (6.1)
       ≥7 cm21 (2.5)
      Clinical N stage
       N0739 (89.7)
       N159 (7.2)
       N225 (3.0)
       N31 (0.1)
      BMI, Body mass index; FEV1, forced expiratory volume in 1 second; GERD, gastroesophageal reflux disease; RBCs, red blood cells.

      30-Day Postoperative Complication Rates

      At least 1 complication occurred in 39.6% of patients, including major complications (see the Methods) in 7.3% (Table 2). Among the most common complications were atrial arrhythmia (11.7%) and pneumonia (4.1%). In general, patients who developed adverse events were more likely to be male, ≥70 years old, undergo upper lobectomy, undergo open surgery, have a hiatal hernia, and receive packed RBCs intraoperatively (Table 3).
      Table 2Complications after lobectomy for lung cancer
      n (%)
      Column is not additive because complications are not mutually exclusive.
      At least 1 complication
      Patients who developed any complication.
      326 (39.6)
      Major complication
      At least 1 of the following: pneumonia, ARDS, bronchopleural fistula, pulmonary embolism, mechanical ventilation for >48 hours, respiratory failure, tracheostomy, myocardial infarction, or nonspecified other event requiring the operating room with anesthesia.
      60 (7.3)
      Pulmonary complications
       Pneumonia34 (4.1)
       Pleural effusion18 (2.2)
       Pneumothorax22 (2.7)
       Atelectasis16 (1.9)
       ARDS4 (0.5)
       Bronchopleural fistula1 (0.1)
       Pulmonary embolism6 (0.7)
       Respiratory failure19 (2.3)
       Other pulmonary complications
      At least 1 of the following: postoperative air leak >5 days, initial mechanical ventilation support for > 48 hours, tracheostomy, nonspecified other pulmonary complications.
      119 (14.4)
      Cardiovascular complications
       Atrial arrhythmia96 (11.7)
       Ventricular arrhythmia2 (0.2)
       Myocardial infarction1 (0.1)
       Other cardiovascular complications
      At least 1 of the following: deep venous thrombosis, nonspecified other cardiovascular complication.
      15 (1.8)
      Noncardiopulmonary complications
       Ileus8 (1.0)
       Urinary tract infection34 (4.1)
       Empyema5 (0.6)
       Sepsis1 (0.1)
       Other complications
      At least 1 of the following: unanticipated postoperative invasive procedure, Clostridium difficile infection, other gastrointestinal complication, transfusion, urinary retention, discharged with Foley, surgical-site infection, nonspecified infection requiring antibiotics, new central neurologic event, laryngeal nerve paresis, delirium tremens, nonspecified other neurologic complication, renal failure, chylothorax, nonspecified other event requiring the operating room with anesthesia, or unexpected intensive care unit admission.
      152 (18.4)
      ARDS, Acute respiratory distress syndrome.
      Column is not additive because complications are not mutually exclusive.
      Patients who developed any complication.
      At least 1 of the following: pneumonia, ARDS, bronchopleural fistula, pulmonary embolism, mechanical ventilation for >48 hours, respiratory failure, tracheostomy, myocardial infarction, or nonspecified other event requiring the operating room with anesthesia.
      § At least 1 of the following: postoperative air leak >5 days, initial mechanical ventilation support for > 48 hours, tracheostomy, nonspecified other pulmonary complications.
      At least 1 of the following: deep venous thrombosis, nonspecified other cardiovascular complication.
      At least 1 of the following: unanticipated postoperative invasive procedure, Clostridium difficile infection, other gastrointestinal complication, transfusion, urinary retention, discharged with Foley, surgical-site infection, nonspecified infection requiring antibiotics, new central neurologic event, laryngeal nerve paresis, delirium tremens, nonspecified other neurologic complication, renal failure, chylothorax, nonspecified other event requiring the operating room with anesthesia, or unexpected intensive care unit admission.
      Table 3Characteristics of lobectomy patients with or without postoperative complications following lobectomy and multivariable logistic regression for any postoperative complications
      Any postoperative complicationMultivariable logistic regression
      Covariaten (%)P valueOdds ratio (95% CI)P value
      Sex
       Female169 (35.1).002Ref
       Male157 (45.8)1.51 (1.11-2.06).01
      Age, y
       <70158 (34.2)<.001Ref
       ≥70168 (46.4)1.55 (1.13-2.11).01
      Race
       White282 (39.7).88Ref
       Not White44 (38.9)0.96 (0.22-1.48).84
      BMI
       <25114 (41.3).25Ref
       25-29.9120 (41.7)0.90 (0.62-1.30).64
       ≥3092 (35.4)0.70 (0.47-1.04).08
      Laterality
       Left123 (39.7).96Ref
       Right203 (39.5)1.02 (0.75-1.39).91
      Lobe
       Upper213 (43.0).01Ref
       Middle19 (26.0)0.55 (0.31-0.99).11
       Lower94 (36.7)0.78 (0.56-1.08).81
      Active smoker
       No244 (38.9).50Ref
       Yes82 (41.6)1.08 (0.75-1.54).69
      Preoperative chemotherapy
       No306 (39.9).47Ref
       Yes20 (35.1)0.47 (0.24-0.93).03
      Previous radiation therapy
       No304 (39.0).19Ref
       Yes22 (48.9)1.76 (0.87-3.55).12
      Minimally invasive vs open
       Minimally invasive263 (37.6).01Ref
       Open63 (50.4)1.51 (0.97-2.35).07
      FEV1 % predicted
       >80201 (38.1).50Ref
       ≤80115 (42.1)1.03 (0.75-1.42).57
       Missing10 (43.5)1.44 (0.59-3.53).44
      Asthma
       No263 (39.1).55Ref
       Yes63 (41.7)1.34 (0.90-1.97).15
      Past pneumonia
       No265 (38.2).06Ref
       Yes61 (46.9)1.23 (0.82-1.83).31
      Diabetes
       No268 (39.1).57Ref
       Yes58 (41.7)1.07 (0.71-1.62).75
      Hypertension
       No115 (36.3).13Ref
       Yes211 (41.6)1.15 (0.83-1.60).40
      Coronary artery disease
       No268 (38.6).17Ref
       Yes58 (45.0)1.02 (0.66-1.56).94
      Hiatal hernia
       No146 (35.8).03Ref
       Yes180 (43.3)1.40 (1.03-1.90).03
      GERD
       No216 (42.8).02Ref
       Yes110 (34.5)0.76 (0.52-1.10).16
      Preoperative acid-suppressive therapy
       No228 (41.2).18Ref
       Yes98 (36.3)0.91 (0.62-1.34).64
      Intraoperative RBCs
       No309 (38.5)<.001Ref
       Yes17 (80.9)4.80 (1.51-15.20).01
      CI, Confidence interval; Ref, reference; BMI, body mass index; FEV1, forced expiratory volume in 1 second; GERD, gastroesophageal reflux disease; RBCs, red blood cells.

      Predictors of at Least One 30-Day Postoperative Complication

      Multivariable logistic regression analyses were performed to determine predictors of at least 1 complication following lobectomy (Table 3). Male sex (odds ratio [OR], 1.51, 95% confidence interval [CI], 1.11-2.06, P = .01), age ≥70 years (OR, 1.55; 95% CI, 1.13-2.11, P = .01), hiatal hernia (OR, 1.40; 95% CI, 1.03-1.90, P = .03), and intraoperative RBCs (OR, 4.80; 95% CI, 1.51-15.20, P = .01) were significant risk factors. Interestingly, chemotherapy in the 6 months before lobectomy appeared to be protective (OR, 0.47; 95% CI, 0.24-0.93, P = .03).

      Predictors of 30-Day Postoperative Cardiopulmonary Complications

      We performed a more focused evaluation of cardiopulmonary complications, as these could be supported by the anatomic and physiologic changes associated with hiatal hernia and GERD (Figure 1). For postoperative pneumonia, active smoking (OR, 2.24; 95% CI, 1.01-4.96, P = .048), chemotherapy in the 6 months before lobectomy (OR, 4.16; 95% CI, 1.28-13.48, P = .02), and receiving intraoperative RBCs (OR, 3.87; 95% CI, 1.01-14.78, P = .048) were identified as significant risk factors (Table E1). Hiatal hernia and GERD were not significantly associated with the risk of postoperative pneumonia. BMI ≥30 appeared to be protective (OR, 0.23; 95% CI, 0.06-0.87, P = .03). For postoperative atrial arrhythmia, male sex (OR, 2.18; 95% CI, 1.35-3.52, P = .001), age ≥70 years (OR, 1.84; 95% CI, 1.13-2.98, P = .01), previous radiation therapy (OR, 3.14; 95% CI, 1.26-7.77, P = .01), open surgery (OR, 2.17; 95% CI, 1.18-3.97, P = .01), asthma (OR, 1.92; 95% CI, 1.08-3.40, P = .03), hiatal hernia (OR, 1.64; 95% CI, 1.02-2.62, P = .04), and receiving intraoperative RBCs (OR, 3.10; 95% CI, 1.10-8.70, P = .03) were identified as risk factors (Figure 2, Table E2).
      Figure thumbnail gr1
      Figure 1Likelihood of developing postoperative complications within 30 days after lobectomy for lung cancer in the presence of (A) hiatal hernia or (B) GERD. Odds ratios were obtained in separate logistic regression models for every complication, which, besides hiatal hernia and GERD, were also adjusted for sex, age, race, BMI, tumor laterality, lobe involved, smoking status, preoperative chemotherapy, previous radiation, surgical approach (minimally invasive vs open), FEV1% predicted, asthma, history of pneumonia, diabetes, hypertension, coronary artery disease, preoperative acid-suppressive therapy, and intraoperative transfusion (see and Table E1, Table E2, Table E3, Table E4). GERD, Gastroesophageal reflux disease.
      Figure thumbnail gr2
      Figure 2Graphical abstract summarizing the study methods, results, and implications.

      Predictors of 30-Day Postoperative Readmission and Mortality

      None of the assessed factors were significantly associated with 30-day readmission on adjusted analysis (Table E3). The risk of 30-day mortality was significantly elevated in patients who had asthma (OR, 7.61; 95% CI, 1.45-39.99, P = .02) and underwent open surgery (OR, 8.25; 95% CI, 1.39-49.06, P = .02) (Table E4). Neither GERD nor hiatal hernia were predictors of readmission or mortality.

      Distribution of Preoperative Acid-Suppressive Therapy and Complications by Hiatal Hernia and GERD Status

      The prevalence of preoperative acid-suppressive therapy differed by hiatal hernia and GERD status. Preoperative acid-suppressive therapy was more prevalent among patients with GERD only (65.4%) or with both GERD and hiatal hernia (67.2%) than in patients who only had a hiatal hernia (14.5%) or neither GERD nor hiatal hernia (9.0%). Patients with only GERD had the lowest frequency of any postoperative complication (31.5%) and atrial arrhythmia (7.7%), whereas patients with only hiatal hernia had the greatest (48.9% and 17.2%, respectively; Table E5). For patients with hiatal hernia, GERD, or both, the rates of any complication were consistently lower for patients receiving preoperative acid-suppressive therapy compared with patients who were not receiving preoperative acid-suppressive therapy. However, there was no clear trend in pneumonia or atrial arrhythmia rates for patients with hiatal hernia, GERD, or both based on preoperative acid-suppressive therapy status (Table E6).

      Comment

      Our objective was to evaluate GERD and hiatal hernia as risk factors for complications after lobectomy for lung cancer. This is the first study to identify hiatal hernia as an independent risk factor for postlobectomy complications, in particular for atrial arrhythmia. Atrial fibrillation remains one of the most common complications after pulmonary resection and has been associated with increased short-term morbidity, mortality, and decreased long-term survival.
      • Ishibashi H.
      • Wakejima R.
      • Asakawa A.
      • Baba S.
      • Nakashima Y.
      • Seto K.
      • et al.
      Postoperative atrial fibrillation in lung cancer lobectomy—analysis of risk factors and prognosis.
      ,
      • Imperatori A.
      • Mariscalco G.
      • Riganti G.
      • Rotolo N.
      • Conti V.
      • Dominioni L.
      Atrial fibrillation after pulmonary lobectomy for lung cancer affects long-term survival in a prospective single-center study.
      Previous studies have described an association between hiatal hernia and atrial fibrillation in the general hospital population and among patients scheduled for cardiac ablation.
      • Roy R.R.
      • Sagar S.
      • Bunch T.J.
      • Aman W.
      • Crusan D.J.
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      • et al.
      Hiatal hernia is associated with an increased prevalence of atrial fibrillation in young patients.
      ,
      • Głowacki J.
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      • Suchodolski A.
      • Wasilewski J.
      Small hiatal hernia as a risk factor of atrial fibrillation.
      While the mechanism is unknown, hiatal hernia has been hypothesized to cause atrial fibrillation through direct mechanical or reflux-induced inflammatory irritation of the left atria.
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      • Roy R.R.
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      • Aman W.
      • Crusan D.J.
      • Srivathsan K.
      • et al.
      Hiatal hernia is associated with an increased prevalence of atrial fibrillation in young patients.
      Mechanical irritation, potentially enhanced by intraoperative manipulation and lobectomy-associated anatomical changes, may partially explain our findings.
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      • Yamamoto S.
      • Kataoka D.
      • Iyano K.
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      • et al.
      Analysis of the anatomic changes in the thoracic cage after a lung resection using magnetic resonance imaging.
      We observed that patients with only hiatal hernia—a population that may include a subset of patients with occult and untreated reflux—had lower rates of preoperative acid-suppressive therapy but a greater prevalence of developing at least 1 complication, as well as pneumonia and atrial arrhythmia, than patients with both GERD and hiatal hernia. We considered the possibility that preoperative acid-suppressive therapy was having a protective effect, however, were not able to confirm this in multivariable analyses. This evaluation may have been confounded by our standard to administer postoperative acid-suppressive therapy for ulcer prophylaxis regardless of GERD status. In other studies, long-term acid-suppressive therapy has actually been associated with increased complications such as pneumonia, possibly due to alterations in the pH or the microbiome of refluxed material.
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      • Kumar A.B.
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      • Eom C.-S.
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      • Lee K.-S.
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      Interestingly, the prevalence of hiatal hernia in our study population was 50.5%, which is more than twice the estimated prevalence of 15% to 20% in the general population.
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      • Lipham J.C.
      Which hiatal hernia's need to be fixed? Large, small or none?.
      This is likely the result of our diagnostic approach of having a dedicated radiologist specifically focusing on anatomy at the hiatus, which would increase sensitivity, or potentially shared risk factors for the development of lung cancer and esophagitis (eg, age, smoking/chronic obstructive pulmonary disease).
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      • Munden R.F.
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      Pathophysiology of gastroesophageal reflux in patients with chronic pulmonary obstructive disease is linked to an increased transdiaphragmatic pressure gradient and not to a defective esophagogastric barrier.
      GERD, in contrast, did not increase the risk for any complication following lobectomy in our study. Although reflux has been associated with atrial fibrillation
      • Roman C.
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      • Muresan L.
      • Picos A.
      • Dumitrascu D.L.
      Atrial fibrillation in patients with gastroesophageal reflux disease: a comprehensive review.
      and pneumonia
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      • Wang C.-Y.
      • et al.
      Risk of pneumonia in patients with gastroesophageal reflux disease: a population-based cohort study.
      in the general population, information about the implications of GERD in patients with lung cancer undergoing lobectomy is sparse. Our findings are in line with another study in which GERD was not a risk factor for unfavorable disposition or mortality following lobectomy.
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      • Tsalantsanis A.
      • Moodie C.C.
      • Garrett J.R.
      • et al.
      Effect of insurance type on perioperative outcomes after robotic-assisted pulmonary lobectomy for lung cancer.
      The incomplete overlap between hiatal hernia and GERD, which also has been demonstrated by other investigators,
      • Sgouros S.N.
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      • et al.
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      ,
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      • Bredenoord A.J.
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      could indicate differences in pathophysiology and risk profile. A large population-based study, for example, attempted to elucidate the interplay between GERD and esophagitis. Similar to our findings, GERD alone was not associated with atrial fibrillation. However, in the presence of esophagitis, for which hiatal hernia is a strong risk factor, the risk of atrial fibrillation significantly increased.
      • Bunch T.J.
      • Packer D.L.
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      • Gersh B.J.
      • et al.
      Long-term risk of atrial fibrillation with symptomatic gastroesophageal reflux disease and esophagitis.
      Given the high complication rates among patients with hiatal hernia only in our study, it is possible that this group included a subpopulation with undiagnosed reflux esophagitis.
      Several other risk factors for postlobectomy complications were identified. Open surgery, for example, was associated with an increased risk of atrial fibrillation and approached significance as a risk factor for at least one complication. While surgical approach has been clearly correlated with postoperative complications in the literature, the evidence for atrial fibrillation is mixed.
      • Kent M.
      • Wang T.
      • Whyte R.
      • Curran T.
      • Flores R.
      • Gangadharan S.
      Open, video-assisted thoracic surgery, and robotic lobectomy: review of a national database.
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      • Lee S.H.
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      ,
      • Park B.J.
      • Zhang H.
      • Rusch V.W.
      • Amar D.
      Video-assisted thoracic surgery does not reduce the incidence of postoperative atrial fibrillation after pulmonary lobectomy.
      Moreover, we identified an association between neoadjuvant chemotherapy within 6 months before lobectomy and postoperative pneumonia, which is partially congruent with the findings of previous studies.
      • Lee J.Y.
      • Jin S.-M.
      • Lee C.-H.
      • Lee B.-J.
      • Kang C.-H.
      • Yim J.-J.
      • et al.
      Risk factors of postoperative pneumonia after lung cancer surgery.
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      • Schussler O.
      • Alifano M.
      • Dermine H.
      • Strano S.
      • Casetta A.
      • Sepulveda S.
      • et al.
      Postoperative pneumonia after major lung resection.
      Interestingly, neoadjuvant chemotherapy within 6 months before lobectomy appeared to be protective against any complication for our study sample, but this represented a small subgroup that may have been influenced by health related selection effects such as a higher threshold for medical clearance and optimization before surgery. We also identified an association between previous radiation therapy and postoperative atrial arrhythmia. Although radiation therapy has been implicated as a risk factor for atrial fibrillation and other arrhythmias in cancer patients, presumably through injury and fibrosis of the cardiac conduction system,
      • Herrmann J.
      Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia.
      other studies failed to find an association.
      • Ishibashi H.
      • Wakejima R.
      • Asakawa A.
      • Baba S.
      • Nakashima Y.
      • Seto K.
      • et al.
      Postoperative atrial fibrillation in lung cancer lobectomy—analysis of risk factors and prognosis.
      ,
      • Hollings D.D.
      • Higgins R.S.D.
      • Faber L.P.
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      • Liptay M.J.
      • Basu S.
      • et al.
      Age is a strong risk factor for atrial fibrillation after pulmonary lobectomy.
      The median BMI was very similar among patients with and without hiatal hernia and GERD diagnosis. However, a BMI ≥30 was associated with a decreased risk of postoperative pneumonia, which may be a reflection of greater nutritional reserves aiding during the postoperative recovery period. In fact, there is considerable disagreement within the literature about the effect of obesity on pneumonia following lung cancer surgery, as some studies also found a protective effect of obesity or higher BMI,
      • Thomas P.A.
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      • Le Pimpec-Barthes F.
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      • Porte H.
      • et al.
      National perioperative outcomes of pulmonary lobectomy for cancer: the influence of nutritional status.
      • Díaz-Ravetllat V.
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      • Torres A.
      Risk factors of postoperative nosocomial pneumonia after resection of bronchogenic carcinoma.
      • Wang Z.
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      • Shi L.
      • Li F.-Y.
      • Lin N.-M.
      Risk factors of postoperative nosocomial pneumonia in stage I-IIIa lung cancer patients.
      whereas other studies have found obesity to be a risk factor.
      • Simonsen D.F.
      • Søgaard M.
      • Bozi I.
      • Horsburgh C.R.
      • Thomsen R.W.
      Risk factors for postoperative pneumonia after lung cancer surgery and impact of pneumonia on survival.
      ,
      • Launer H.
      • Nguyen D.V.
      • Cooke D.T.
      National perioperative outcomes of pulmonary lobectomy for cancer in the obese patient: a propensity score matched analysis.
      ,
      • Montané B.
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      • Thau M.R.
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      • et al.
      Effect of obesity on perioperative outcomes after robotic-assisted pulmonary lobectomy:retrospective study of 287 patients.

      Limitations

      Our study has several limitations. As a single institution series of just more than 800 cases, it is possible that important associations between hiatal hernia, GERD, and postoperative complications were missed because of power. For example, our power to detect the observed difference in pneumonia rate associated with hiatal hernia was only 18.6%. The gold standard for diagnosis of hiatal hernia is esophagogastroduodenoscopy or barium-swallow esophagram rather than CT,
      • Weitzendorfer M.
      • Köhler G.
      • Antoniou S.A.
      • Pallwein-Prettner L.
      • Manzenreiter L.
      • Schredl P.
      • et al.
      Preoperative diagnosis of hiatal hernia: barium swallow X-ray, high-resolution manometry, or endoscopy?.
      but the former are not routinely collected before lobectomy and thus cannot be used for patient risk stratification. Hiatal hernia diagnosis can be subjective and may, therefore, vary highly across radiologist reviews.
      • Roman S.
      • Kahrilas P.J.
      The diagnosis and management of hiatus hernia.
      In an attempt to be consistent, a single radiologist evaluated all patient scans based on previously published criteria to classify hiatal hernias.
      • Dodds W.J.
      1976 Walter B. Cannon Lecture: current concepts of esophageal motor function: clinical implications for radiology.
      • Noth I.
      • Zangan S.M.
      • Soares R.V.
      • Forsythe A.
      • Demchuk C.
      • Takahashi S.M.
      • et al.
      Prevalence of hiatal hernia by blinded multidetector CT in patients with idiopathic pulmonary fibrosis.
      • Ginalski J.M.
      • Schnyder P.
      • Moss A.A.
      • Brasch R.C.
      Incidence and Significance of a Widened Esophageal Hiatus at CT Scan.
      However, a radiologist overreading existing CT scans looking solely for hiatal hernia may have increased the observed prevalence of hiatal hernia in our patient population compared with standard radiology reads. However, we recognize that there may be nuanced implications based on relative size of hernia and morphology that were not able to be characterized because CT scans provide only a “snapshot” of hiatal hernias, most of which are sliding hernias and whose maximal dimensions are not accurately measured by CT. Moreover, comorbidities like GERD may be inconsistently documented in the medical record, and proper diagnosis and treatment are likely influenced by socioeconomic factors affecting access to care such as income or geographic proximity to medical facilities. Our institution's standard to administer postoperative acid-suppressive therapy for ulcer prophylaxis regardless of GERD status and postoperative calcium channel blockers for atrial fibrillation prophylaxis may have affected the postoperative complication rates and confounded our analyses, particularly between GERD and postoperative complications. However, our study sample's 30-day postoperative pneumonia and atrial arrhythmia complication rates closely approximated previously reported rates of postlobectomy pneumonia
      • Simonsen D.F.
      • Søgaard M.
      • Bozi I.
      • Horsburgh C.R.
      • Thomsen R.W.
      Risk factors for postoperative pneumonia after lung cancer surgery and impact of pneumonia on survival.
      ,
      • Liu G.-W.
      • Sui X.-Z.
      • Wang S.-D.
      • Zhao H.
      • Wang J.
      Identifying patients at higher risk of pneumonia after lung resection.
      ,
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      • Kosinski A.S.
      • Magee M.J.
      • Dokholyan R.
      • Jacobs J.P.
      • et al.
      The Society of Thoracic Surgeons composite score for rating program performance for lobectomy for lung cancer.
      ,
      • Kotova S.
      • Wang M.
      • Lothrop K.
      • Grunkemeier G.
      • Merry H.E.
      • Handy J.R.
      CHADS2 score predicts postoperative atrial fibrillation in patients undergoing elective pulmonary lobectomy.
      ,
      • Reddy R.M.
      • Gorrepati M.L.
      • Oh D.S.
      • Mehendale S.
      • Reed M.F.
      Robotic-assisted versus thoracoscopic lobectomy outcomes from high-volume thoracic surgeons.
      and atrial arrhythmia.
      • Imperatori A.
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      • Rotolo N.
      • Conti V.
      • Dominioni L.
      Atrial fibrillation after pulmonary lobectomy for lung cancer affects long-term survival in a prospective single-center study.
      ,
      • Reddy R.M.
      • Gorrepati M.L.
      • Oh D.S.
      • Mehendale S.
      • Reed M.F.
      Robotic-assisted versus thoracoscopic lobectomy outcomes from high-volume thoracic surgeons.
      • Garner M.
      • Routledge T.
      • King J.E.
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      • Veres L.
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      • et al.
      New-onset atrial fibrillation after anatomic lung resection: predictive factors, treatment and follow-up in a UK thoracic centre.
      • Onaitis M.
      • D'Amico T.
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      • Harpole D.
      Risk factors for atrial fibrillation after lung cancer surgery: analysis of The Society of Thoracic Surgeons General Thoracic Surgery database.
      Finally, a considerable proportion of GERD is asymptomatic, but the GERD prevalence in our study approximates recent estimates of GERD in the US population.
      • Delshad S.D.
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      Prevalence of gastroesophageal reflux disease and proton pump inhibitor-refractory symptoms.

      Conclusions

      Hiatal hernia was identified as a novel risk factor for complications after pulmonary lobectomy, particularly for atrial arrhythmia. The increased risk should be considered in the perioperative consultation with lobectomy patients and potentially be considered as patients are risk stratified for prophylaxis. Further study to more completely characterize the relationship of hiatal hernia and GERD with surgical outcomes in lung cancer is warranted.

      Conflict of Interest Statement

      D.J.B. is a member of the Commission on Cancer and receives nonfinancial support from Epic science , which performs assays for free, but this work is not directly tied to or supported by either. All other authors reported no conflicts of interest.
      The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

      Appendix E1

      Table E1Characteristics of lobectomy patients with or without postoperative pneumonia following lobectomy and multivariable logistic regression for postoperative pneumonia
      Any postoperative pneumoniaMultivariable logistic regression
      Covariaten (%)P valueOdds ratio (95% CI)P value
      Sex
       Female14 (2.9).04Ref
       Male20 (5.8)1.96 (0.92-4.17).08
      Age, y
       <7017 (3.7).47Ref
       ≥7017 (4.7)1.22 (0.56-2.62).62
      Race
       White28 (3.9).50Ref
       Not White6 (5.3)1.34 (0.49-3.64).57
      BMI
       <2515 (5.4)<.001Ref
       25-29.916 (5.6)0.87 (0.39-1.97).16
       ≥303 (1.1)0.23 (0.06-0.87).03
      Laterality
       Left11 (3.5).52Ref
       Right23 (4.5)1.28 (0.58-2.82).54
      Lobe
       Upper25 (5.1).01Ref
       Middle1 (1.4)0.35 (0.04-2.81).40
       Lower8 (3.1)0.73 (0.31-1.74).74
      Active smoker
       No20 (3.2).02Ref
       Yes14 (7.1)2.24 (1.01-4.96).048
      Preoperative chemotherapy
       No28 (3.7).01Ref
       Yes6 (10.5)4.16 (1.28-13.48).02
      Previous radiation therapy
       No32 (4.1).28Ref
       Yes2 (4.4)0.38 (0.06-2.33).30
      Minimally invasive vs open
       Minimally Invasive26 (3.7).17Ref
       Open8 (6.4)0.96 (0.36-2.56).93
      FEV1 % predicted
       >8019 (3.6).50Ref
       ≤8014 (5.1)1.13 (0.53-2.43).96
       Missing1 (4.3)1.36 (0.16-11.88).82
      Asthma
       No29 (4.3).58Ref
       Yes5 (3.3)0.79 (0.28-2.26).66
      Past pneumonia
       No25 (3.6).08Ref
       Yes9 (6.9)1.76 (0.75-4.13).20
      Diabetes
       No29 (4.2).73Ref
       Yes5 (3.6)0.93 (0.31-2.75).89
      Hypertension
       No11 (3.5).45Ref
       Yes23 (4.5)1.35 (0.59-3.09).48
      Coronary artery disease
       No26 (3.7).20Ref
       Yes8 (6.2)1.30 (0.51-3.36).58
      Hiatal hernia
       No14 (3.4).32Ref
       Yes20 (4.8)1.52 (0.72-3.24).28
      GERD
       No25 (5.0).13Ref
       Yes9 (2.8)0.48 (0.18-1.33).16
      Preoperative acid-suppressive therapy
       No23 (4.1).96Ref
       Yes11 (4.1)1.68 (0.64-4.42).29
      Intraoperative RBCs
       No309 (38.5).01Ref
       Yes4 (19.0)3.87 (1.01-14.78).048
      CI, Confidence interval; Ref, reference; BMI, body mass index; FEV1, forced expiratory volume in 1 second; GERD, gastroesophageal reflux disease; RBCs, red blood cells.
      Table E2Characteristics of lobectomy patients with or without postoperative atrial arrhythmia following lobectomy and multivariable logistic regression for postoperative atrial arrhythmia
      Postoperative atrial arrhythmiaMultivariable logistic regression
      Covariaten (%)P valueOdds ratio (95% CI)P value
      Sex
       Female42 (8.7).002Ref
       Male54 (15.7)2.18 (1.35-3.52).001
      Age, y
       <7042 (9.1).01Ref
       ≥7054 (14.9)1.84 (1.13-2.98).01
      Race
       White87 (12.2).19Ref
       Not White9 (8.0)0.60 (0.28-1.27).18
      BMI
       <2528 (10.1).60Ref
       25-29.937 (12.8)1.21 (0.68-2.13).62
       ≥3031 (11.9)1.15 (0.61-2.15).87
      Laterality
       Left28 (9.0).07Ref
       Right68 (13.2)1.49 (0.90-2.45).12
      Lobe
       Upper58 (11.7).98Ref
       Middle8 (11.0)1.20 (0.51-2.81).76
       Lower30 (11.7)1.10 (0.66-1.83).98
      Active smoker
       No76 (12.1).45Ref
       Yes20 (10.2)0.97 (0.54-1.72).91
      Preoperative chemotherapy
       No89 (11.6).88Ref
       Yes7 (12.3)0.48 (0.17-1.38).17
      Previous radiation therapy
       No85 (10.9).01Ref
       Yes11 (24.4)3.14 (1.26-7.77).01
      Minimally invasive vs open
       Minimally invasive71 (10.2).002Ref
       Open25 (20.0)2.17 (1.18-3.97).01
      FEV1 % predicted
       >8064 (12.1).01Ref
       ≤8032 (11.7)0.82 (0.50-1.34).96
       Missing0 (0.0)<.001 (<.001 to >999.99).96
      Asthma
       No75 (11.1).34Ref
       Yes21 (13.9)1.92 (1.08-3.40).03
      Past pneumonia
       No80 (11.5).80Ref
       Yes16 (12.3)0.82 (0.45-1.52).54
      Diabetes
       No82 (12.0).52Ref
       Yes14 (10.1)0.73 (0.38-1.42).35
      Hypertension
       No35 (11.0).67Ref
       Yes61 (12.0)1.01 (0.61-1.66).97
      Coronary artery disease
       No80 (11.5).77Ref
       Yes16 (12.4)0.70 (0.37-1.34).29
      Hiatal hernia
       No38 (9.3).04Ref
       Yes58 (13.9)1.64 (1.02-2.62).04
      GERD
       No67 (13.3).07Ref
       Yes29 (9.1)0.68 (0.38-1.22).19
      Preoperative acid-suppressive therapy
       No67 (12.1).57Ref
       Yes29 (10.7)0.98 (0.55-1.76).95
      Intraoperative RBCs
       No88 (11.0)<.001Ref
       Yes8 (38.1)3.10 (1.10-8.70).03
      CI, Confidence interval; Ref, reference; BMI, body mass index; FEV1, forced expiratory volume in 1 second; GERD, gastroesophageal reflux disease; RBCs, red blood cells.
      Table E3Characteristics of lobectomy patients with or without 30-day readmission following lobectomy and multivariable logistic regression for 30-day readmission
      30-day readmissionMultivariable logistic regression
      Covariaten (%)P valueOdds ratio (95% CI)P value
      Sex
       Female37 (7.8).92Ref
       Male27 (7.9)0.91 (0.52-1.62).76
      Age, y
       <7032 (7.0).31Ref
       ≥7032 (8.9)1.26 (0.73-2.19).41
      Race
       White57 (8.1).52Ref
       Not White7 (6.3)0.83 (0.35-1.93).66
      BMI
       <2521 (7.7).55Ref
       25-29.926 (9.1)1.23 (0.65-2.33).27
       ≥3017 (6.6)0.82 (0.40-1.70).34
      Laterality
       Left19 (6.2).17Ref
       Right45 (8.8)1.49 (0.83-2.67).18
      Lobe
       Upper44 (8.9).01Ref
       Middle5 (6.8)0.65 (0.23-1.80).65
       Lower15 (6.0)0.67 (0.36-1.26).63
      Active smoker
       No53 (8.5).19Ref
       Yes11 (5.6)0.64 (0.32-1.30).22
      Preoperative chemotherapy
       No57 (7.5).08Ref
       Yes7 (12.5)1.00 (0.36-2.80)1.00
      Previous radiation therapy
       No57 (7.4).03Ref
       Yes7 (12.5)2.32 (0.83-6.50).11
      Minimally invasive vs open
       Minimally invasive51 (7.3).20Ref
       Open13 (10.7)1.15 (0.54-2.46).72
      FEV1 % predicted
       >8040 (7.6).03Ref
       ≤8022 (8.1)1.07 (0.60-1.89).97
       Missing2 (8.7)1.09 (0.24-5.05).94
      Asthma
       No53 (7.9).86Ref
       Yes11 (7.5)1.04 (0.51-2.11).91
      Past pneumonia
       No54 (7.8).99Ref
       Yes10 (7.9)0.97 (0.47-2.01).93
      Diabetes
       No51 (7.5).43Ref
       Yes13 (9.5)1.56 (0.77-3.17).22
      Hypertension
       No28 (8.9).37Ref
       Yes36 (7.2)0.71 (0.40-1.27).25
      Coronary artery disease
       No52 (7.5).46Ref
       Yes12 (9.4)1.16 (0.56-2.42).68
      Hiatal hernia
       No31 (7.7).87Ref
       Yes33 (8.0)0.96 (0.56, 1.65).88
      GERD
       No35 (7.0).27Ref
       Yes29 (9.1)1.73 (0.91-3.27).10
      Preoperative acid-suppressive therapy
       No43 (7.8).98Ref
       Yes21 (7.9)1.46 (0.74-2.88).27
      Intraoperative RBCs
       No60 (7.5).04Ref
       Yes4 (21.1)2.44 (0.69-8.63).17
      CI, Confidence interval; Ref, reference; BMI, body mass index; FEV1, forced expiratory volume in 1 second; GERD, gastroesophageal reflux disease; RBCs, red blood cells.
      Table E4Characteristics of lobectomy patients with or without postoperative 30-day mortality following lobectomy and multivariable logistic regression for 30-day mortality
      30-day mortalityMultivariable logistic Regression
      Covariaten (%)P valueOdds ratio (95% CI)P value
      Sex
       Female5 (1.1).22Ref
       Male5 (1.5)1.81 (0.43-7.61).42
      Age, y
       <704 (0.9).15Ref
       ≥706 (1.7)2.13 (0.46-9.84).33
      Race
       White8 (1.2).26Ref
       Not White2 (1.8)1.77 (0.29-10.65).53
      BMI
       <256 (2.2).02
       25-29.92 (0.7)0.21 (0.03-1.36).61
       ≥302 (0.8)0.11 (0.01-1.08).18
      Laterality
       Left3 (1.0).24Ref
       Right7 (1.4)2.28 (0.43-12.04).33
      Lobe
       Upper5 (1.0).08Ref
       Middle1 (1.4)1.88 (0.15-23.48).82
       Lower4 (1.6)2.02 (0.42-9.69).66
      Active smoker
       No8 (1.3).29Ref
       Yes2 (1.0)0.45 (0.07-3.08).42
      Preoperative chemotherapy
       No8 (1.1).13Ref
       Yes2 (3.5)0.94 (0.09-9.54).96
      Previous radiation therapy
       No9 (1.2).33Ref
       Yes1 (2.3)1.11 (0.06-19.03).94
      Minimally invasive vs open
       Minimally invasive5 (0.7).01Ref
       Open5 (4.0)8.25 (1.39-49.06).02
      FEV1 % predicted
       >806 (1.2).06Ref
       ≤803 (1.2)0.60 (0.12-2.88).42
       Missing1 (4.3)1.69 (0.08-36.45).61
      Asthma
       No6 (0.9).07Ref
       Yes4 (2.7)7.61 (1.45-39.99).02
      Past pneumonia
       No7 (1.0).14Ref
       Yes3 (2.4)1.52 (0.33-7.06).59
      Diabetes
       No7 (1.1).16Ref
       Yes3 (2.2)6.31 (0.85-47.08).07
      Hypertension
       No4 (1.3).25Ref
       Yes6 (1.2)0.66 (0.13-3.28).61
      Coronary artery disease
       No8 (1.2).28Ref
       Yes2 (1.6)1.43 (0.22-9.30).71
      Hiatal Hernia
       No5 (1.3).25Ref
       Yes5 (1.2)1.01 (0.23-4.45).99
      GERD
       No8 (1.6).13Ref
       Yes2 (0.6)0.15 (0.02-1.29).08
      Preoperative acid-suppressive Therapy
       No7 (1.3).26Ref
       Yes3 (1.1)2.08 (0.30-14.32).46
      Intraoperative RBCs
       No8 (1.0).02Ref
       Yes2 (10.0)6.19 (0.86-44.54).07
      CI, Confidence interval; Ref, reference; BMI, body mass index; FEV1, forced expiratory volume in 1 second; GERD, gastroesophageal reflux disease; RBCs, red blood cells.
      Table E5Distribution of BMI, preoperative acid-suppressive therapy, and complications by hiatal hernia and GERD status
      BMIPreoperative acid-suppressive therapyAny complicationPneumoniaAtrial arrhythmia
      Median (IQR)No, n (%)Yes, n (%)No, n (%)Yes, n (%)No, n (%)Yes n (%)No, n (%)Yes, n (%)
      Neither
      Neither hiatal hernia nor GERD.
      26.6 (23.1, 30.6)253 (91.0)25 (9.0)173 (62.2)105 (37.8)266 (95.7)12 (4.3)250 (89.9)28 (10.1)
      Hiatal hernia only
      Hiatal hernia but no GERD.
      27.5 (24.8, 31.4)194 (85.5)33 (14.5)116 (51.1)111 (48.9)214 (94.3)13 (5.7)188 (82.8)39 (17.2)
      GERD only
      GERD but no hiatal hernia.
      26.8 (22.6, 31.9)45 (34.6)85 (65.4)89 (68.5)41 (31.5)128 (98.5)2 (1.5)120 (92.3)10 (7.7)
      Both
      Both hiatal hernia and GERD.
      27.7 (24.4, 31.9)62 (32.8)127 (67.2)120 (63.5)69 (36.5)182 (96.3)7 (3.7)170 (89.9)19 (10.1)
      BMI, Body mass index; IQR, interquartile range; GERD, gastroesophageal reflux disease.
      Neither hiatal hernia nor GERD.
      Hiatal hernia but no GERD.
      GERD but no hiatal hernia.
      § Both hiatal hernia and GERD.
      Table E6Complication rates relative to preoperative acid-suppressive therapy status for patients divided by hiatal hernia and GERD status
      Any complication rate (%)Pneumonia rate (%)Atrial arrhythmia rate (%)
      Preoperative acid-suppressive therapyPreoperative acid-suppressive therapyPreoperative acid-suppressive therapy
      NoYesNoYesNoYes
      Neither
      Neither hiatal hernia nor GERD.
      3652412916
      Hiatal hernia only
      Hiatal hernia but no GERD.
      4945631718
      GERD only
      GERD but no hiatal hernia.
      362902116
      Both
      Both hiatal hernia and GERD.
      393534811
      GERD, Gastroesophageal reflux disease.
      Neither hiatal hernia nor GERD.
      Hiatal hernia but no GERD.
      GERD but no hiatal hernia.
      § Both hiatal hernia and GERD.

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