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Hiatal Hernia after Esophagectomy: An Underappreciated Complication?
Journal Pre-proof Hiatal Hernia after Esophagectomy: An Underappreciated Complication? Andrew N. Hanna, MD, Isabella Guajardo, MD, Noel Williams, MD, John Kucharczuk, MD, FACS, Daniel T. Dempsey, MD, MBA, FACS PII:
S1072-7515(20)30070-3
DOI:
https://doi.org/10.1016/j.jamcollsurg.2019.12.009
Reference:
ACS 9702
To appear in:
Journal of the American College of Surgeons
Received Date: 16 December 2019 Accepted Date: 16 December 2019
Please cite this article as: Hanna AN, Guajardo I, Williams N, Kucharczuk J, Dempsey DT, Hiatal Hernia after Esophagectomy: An Underappreciated Complication?, Journal of the American College of Surgeons (2020), doi: https://doi.org/10.1016/j.jamcollsurg.2019.12.009. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc. on behalf of the American College of Surgeons.
Hiatal Hernia after Esophagectomy: An Underappreciated Complication? Andrew N Hanna, MD1, Isabella Guajardo, MD2, Noel Williams, MD1, John Kucharczuk, MD, FACS1, Daniel T Dempsey, MD, MBA, FACS1 1 2
Department of Surgery, University of Pennsylvania, Philadelphia, PA Department of Surgery, UC San Diego, San Diego, CA
Disclosure Information: Nothing to disclose. Presented at the Southern Surgical Association 129th Annual Meeting, Hot Springs, VA, December 2019. Corresponding Author: Daniel T Dempsey, MD Professor of Surgery University of Pennsylvania 3400 Spruce Street Philadelphia, PA 19104 Tel: 215-614-0092 Email: [email protected]
Brief Title: Hiatal Hernia after Esophagectomy
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Background: The natural history of hiatal herniation of small and/or large bowel post esophagectomy (HHBPE), in the current era of improving long term survival and evolving surgical technique, is unknown. The aim of this study is to describe the rate and risk factors of HHBPE at our hospital. Methods: Patients undergoing esophagectomy between January, 2011 and June, 2017 were included if both follow up information and axial imaging were available beyond 3 months post esophagectomy. Patient characteristics, disease information, and treatment factors were all included in univariate analysis comparing patients with and without HHBPE, and multivariate regression was used to identify significant independent risk factors associated with HHBPE. Results: Out of 310 esophagectomy patients analyzed, 258 patients were included in the study, with 79 patients (31%) showing evidence of a HHBPE and an overall median follow-up of 24 months; 44/79 (56%) had symptoms possibly referable to HHBPE and 17/79 (22%) underwent surgical repair. On univariate analysis, neoadjuvant therapy (n = 176), higher clinical stage, minimally invasive approach (n = 154), and transhiatal esophagectomy (n = 189) were significant predictors of HHBPE (p<0.05). On multivariate analysis, neoadjuvant therapy and transhiatal approach remained significant independent predictors (p < 0.05). In the 131 patients (51%) that had both factors, the rate of HHBPE was 44%. Conclusions: HHBPE in the current era of neoadjuvant therapy and minimally invasive esophagectomy is common. HHBPE may cause GI symptoms but operation to repair HHBPE is uncommon on intermediate follow up. Further study and long-term follow are required to fully assess the impact of HHBPE and to potentially modify surgical practice to prevent or minimize HHBPE. Keywords: hiatal hernia, esophagectomy, risk factors
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INTRODUCTION Hiatal herniation of small and/or large intestine is a recognized complication of esophagectomy, an operation that disrupts the phrenoesophageal ligament and dilates the hiatus. The natural history of this complication is unclear. A review of the literature revealed a limited number of studies that reported an estimated incidence range of 0.4 to 19.4% (1). These studies also compared different surgical approaches and had a wide range of follow-up intervals. Some authors suggest that hiatal herniation of bowel after esophagectomy is an unusual complication, while others suggest that it is quite common. Furthermore, some authors suggest that bowel herniated through the hiatus after esophagectomy is in danger of strangulation and should be operated upon when diagnosed, while others suggest observation is appropriate for the majority of patients with this finding unless worrisome symptoms ensue (2 - 6). Hiatal herniation of fat after esophagectomy is probably both common and trivial, and the significance of herniation of solid organs is unknown. Repair of hiatal herniation after esophagectomy can be challenging and morbid, and recurrent herniation is common. It may be difficult to prevent hiatal herniation after esophagectomy, but some authors favor routine suturing of the esophageal replacement conduit (usually stomach) to the crural diaphragm (5,6). Other surgeons do this rarely if at all (7,8). It may be worthwhile identifying predictive factors for hiatal herniation of small and/or large bowel post esophagectomy (HHBPE) so that in patients at risk preventive measures may be attempted during esophagectomy and/or closer postoperative follow up may be employed. Hiatal herniation of bowel after esophagectomy is likely to be seen more commonly now because esophagectomy is performed with both increased frequency and increased long term survival (914). Patient survival after esophagectomy has improved overall due to advancements in cancer
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therapeutics and surgical technology. As more patients treated for esophageal cancer survive, the number of patients facing treatment complications will increase. Furthermore, both minimally invasive techniques and transhiatal esophagectomy without thoracotomy are now more often employed for esophagectomy than in the past, and both these factors have been associated with increased risk of post esophagectomy hiatal hernia in some studies. Although post-esophagectomy hiatal hernias were previously reported to occur in the acute post-operative setting, they have recently been found months to years after the initial procedure. Thus it is important for surgeons, oncologists, gastroenterologists, and radiologists to understand the clinical significance of HHBPE. Since 2011, our 3 surgeon team has performed 90% of the esophagectomies in our health system using a standard technique for both open and laparoscopic assisted operations. The purpose of our study was to define the natural history and risk factors for HHBPE, hoping to minimize the confounding effects, seen in some studies, of multiple surgeons using evolving techniques over many years. METHODS All patients undergoing esophagectomy between January 1, 2011 and June 30, 2017 were included in this retrospective analysis with institutional review board approval. Data recorded included age, gender, BMI, smoking history, indication for operation, clinical tumor stage on presentation and neoadjuvant treatment information for cancer patients, date of operation, operating surgeon(s), postoperative imaging results, reoperation for hiatal hernia, and postoperative clinic visit results. All available relevant preoperative and postoperative imaging studies (CT, MRI, CXR) and reports were reviewed for the presence of hiatal herniation of bowel.
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Patients were excluded from study if there was no available imaging beyond 3 months post esophagectomy, but we did not knowingly exclude any patient with early HHBPE. Univariate analysis was used to compare patients with and without HHBPE, and multivariate regression analysis was used to identify significant factors associated with the development of HHBPE. Frequency tables were used to describe discrete variables, with continuous variables described with mean values or normally distributed values and median/interquartile ranges for non-normally distributed variables. Comparisons between patients were performed using MannWhitney U tests for continuous data and Fisher exact tests for discrete variables. Multivariate logistic regression was then used to determine predictors of HHBPE and significant factors of the reduced model were then used to assess the risk of HHBPE in the study cohort. All statistical analyses were performed using R: A Language and Environment for Statistical Computing (Vienna, Austria). RESULTS During the study period, esophagectomy was performed in 310 patients. Fifty-two patients were excluded because of lack of imaging studies beyond 3 months. Thus, 258 patients met entry criteria and were followed for a median of 24 months (IQR, 18 months – 30 months). In the study group of 258 patients the following esophagectomy approaches were used: open Ivor Lewis (n = 46); laparoscopic assisted Ivor Lewis (n = 6); open transhiatal (n = 47); laparoscopic assisted transhiatal (n = 142); open “3 hole” McKeown (n = 11); laparoscopic assisted “3 hole” McKeown (n = 6). The incidence of HHBPE of the entire cohort was 31% (79/258). Patients with HHBPE had a median follow-up of 31.2 months compared with a median follow-up of 22.7 months in patients without HHBPE (p=0.002). All patient characteristics are summarized in Table 1.
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On univariate analysis, the following factors were significantly associated with HHBPE: neoadjuvant chemoradiation (n = 176); laparoscopic assisted technique (n = 154); transhiatal approach (n = 189); and higher clinical stage at presentation. The following factors were not significantly associated with HHBPE on univariate analysis: age, BMI, smoking history, gender, preoperative hiatal hernia, and indication for esophagectomy. On multivariate analysis, shown in Table 2, neoadjuvant treatment and transhiatal approach were significant independent predictors of HHBPE and remained significant on the reduced multivariate regression model. In patients where both factors were present (n=131), HHBPE developed in 58 patients (44%). When no factor or only 1 factor was present, HHBPE developed in 19 (20%) and 3 (10%) patients respectively (Figure 1). Forty-four of the 79 patients with HHBPE (56%) had symptoms possibly caused by the hiatal herniation. Seventeen of these 79 patients (22%) underwent surgical repair of HHBPE, including two patients in the first month postesophagectomy, with no mortality and no bowel resections required. Out of these 17 patients, 5 eventually recurred with 1 requiring an emergent repair. Table 3 describes in detail the outcomes of these 17 patients. Figure 2 shows a representative cross-sectional coronal image of one of these patients with a significant hiatal hernia 3 years after esophagectomy who eventually underwent primary repair with no evidence of recurrence since. DISCUSSION In this analysis of 258 esophagectomy patients with postoperative imaging studies followed for a median of 24 months, we found radiologic evidence of postoperative hiatal herniation of bowel in 79 patients (31%). Over half (56%) of these 79 patients were deemed by
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the surgeon on follow up to have symptoms possibly related to HHBPE, but only 17 of the 44 symptomatic patients (39%) required operation to repair HHBPE. Many patients with HHBPE had mild symptoms, or symptoms that were questionably related to the postoperative hiatal hernia. Thus only 7% of the study population (17/258), and only 22% of patients with HHBPE (17/79) required operation on follow up. There were no deaths related to HHBPE and no bowel resections related to HHBPE. Both preoperative neoadjuvant chemoradiation, and transhiatal without thoracotomy approach (but not laparoscopic assisted operation), were independently associated with increased likelihood of HHBPE. Based on these findings we do not recommend operation for HHBPE unless symptoms are severe or progressive. We do however follow patients indefinitely if they are found to have HHBPE, or if they have had a transhiatal esophagectomy without thoracotomy, or if they have received neoadjuvant treatment. This constitutes the majority of our esophagectomy population, all of whom have CT scan of chest and abdomen within the first year post esophagectomy. Follow up includes patient and family education about symptoms which may indicate incarceration or strangulation of herniated transhiatal intestine. The incidence of HHBPE found in our study is higher than any published series, as summarized in Table 4 and Table 5 (2-8,15-20). Though our follow up is longer than some studies, this is probably not a major reason for this finding. Our higher incidence of HHBPE is likely due to several factors. Firstly, we looked for HHBPE in every patient included in our series with postoperative imaging and if imaging findings were equivocal for HHBPE, we considered the patients to have had HHBPE. Analysis of published studies clearly shows that the occurrence of postesophagectomy hiatal hernia is significantly more common in studies that utilized and scrutinized postop imaging in the study population. As with so many things in
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surgery, if you do not look for it you will not find it. For example, Price et al reported on 15 patients reoperated on at the Mayo Clinic for hiatal herniation of abdominal contents at a median of 1.75 years after esophagectomy at that facility (4). These patients were accumulated over many years, and represented only 0.69% of the 2,182 esophagectomies performed during that time at Mayo Rochester, most of which were Ivor Lewis operations. While the authors concluded that HHBPE is unusual, the lack of routine imaging makes this conclusion suspect and an incidence of less than 1% is likely a substantial underestimation of the true incidence of HHBPE. Similarly, Kent et al from Pittsburgh reported a 2% incidence of HHBPE in 1075 patients without routine review of postop imaging (2). Other large series which included postoperative imaging show a much higher likelihood of post esophagectomy hiatal herniation. Ganeshan et al from MD Anderson reported 67 diaphragmatic hernias (67/440=15%) at a median 2 years after esophagectomy; there were 33 patients with HHBPE (33/440=7.5%). (4) At a median follow up of 8 months, Crespin et al at the University of Washington found postoperative hiatal herniation in 22 of 192 esophagectomy patients (22/192=11%) (6). Similarly, from Europe Brenkman et al reported 45 postoperative hiatal hernias in 488 esophagectomy patients followed for a median of 18 months (45/488=9%) (7). These studies which look for HHBPE with postoperative imaging identify this complication much more commonly than those which rely on symptoms. This observation is consistent with our belief that most patients with HHBPE have minimal symptoms. Secondly, most of the patients in our series were treated with transhiatal esophagectomy and a laparoscopic assisted approach. It has been suggested in the literature that both factors increase the likelihood of HHBPE. Gooszen et al from Amsterdam applied multivariate analysis to a large series of patients (n=851) and found that minimally invasive Ivor Lewis was associated
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with increased risk of HHBPE (15). Matthews et al from UK found significantly more postoperative hiatal hernias in patients having minimally invasive esophagectomy (27/285=10%) compared to those having an open operation (4/221=2%) (21). However, on multivariate analysis, the minimally invasive approach was not a significant predictor of HHBPE in our study. When comparing publications where most of the esophagectomies were done minimally invasively to those where most were done open, the incidence of HHBPE is about the same. Whether a minimally invasive approach conclusively increases the risk of hiatal hernia is still therefore open to debate. We think that the data favoring transhiatal resection without thoracotomy as a risk factor for HHBPE is much stronger. In the current series it was by far the strongest risk factor. Ganeshan et al also found that transhiatal esophagectomy was a significant risk factor in their study population of 440 patients (4). Also when the literature is scrutinized, publications where transhiatal esophagectomy is performed most commonly have a higher incidence of HHBPE than those that use the transhiatal approach less frequently. It is likely that our heavy reliance on transhiatal esophagectomy without thoracotomy, and perhaps our now routine use of a laparoscopic assisted approach, contributed substantially to our high incidence of HHBPE. We also noted a significantly higher rate of HHBPE in patients treated with neoadjuvant chemoradiation, a significant risk factor on multivariate analysis. It is possible that chemoradiation slows the development of postoperative adhesions and favors transhiatal migration of bowel into the chest and mediastinum. It is also possible that it defines more advanced tumor stage requiring more substantial perihiatal resection which favors postoperative herniation.
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Finally, there are undoubtedly technical factors associated with HHBPE but many of these are hard to measure. We do not routinely suture the conduit to the crural diaphragm nor do we routinely attempt to reconstruct the crura. While some surgeons maintain that these are important steps to prevent hiatal herniation after esophagectomy, conclusive evidence in this regard is wanting. Orringer routinely sutures the gastric conduit to the crural diaphragm (22). Careful review of the literature suggests that the incidence of HHBPE is about the same whether or not the conduit is sutured to the crural diaphragm. Brenkman et al and Severino et al in two European series with good imaging follow up specifically state that surgeons do not fix the conduit to the diaphragm, and they report an incidence of HHBPE of 9% and 8% respectively (7, 8). In the US, Bronson et al from OHSU and Crespin et al from University of Washington report HHBPE in 8% and 11% of their patients, respectively, when the conduit is routinely sutured to the crura (5,6). Thus it is not clear whether the lack of crural fixation contributed to our high rate of HHBPE. Our experience and review of the literature suggest that HHBPE is usually not dangerous. Many patients with this complication have minimal symptoms. In the absence of worsening symptoms, the risk of bowel strangulation is very low, quite analogous to paraesophageal hernia (PEH). We had no deaths or bowel strangulation in our series. Perusal of the articles summarized in Table 4 and Table 5 shows only seven deaths and seven bowel resections related to HHBPE out of thousands of esophagectomy patients. Recurrence after repair is quite common (also analogous to PEH). Injudicious repair of asymptomatic HHPBE should be avoided. CONCLUSIONS We found HHBPE in 31% of our current series of esophagectomy patients. Transhiatal resection and preoperative chemoradiation were significant risk factors for HHBPE on
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multivariate analysis, and the fact that the majority of our patients had both factors may have contributed to our high incidence of postoperative herniation. Whether the now routine use of the laparoscopic assisted approach and/or the lack of fixation of the conduit to the crura increased the risk of postoperative herniation in our series is unclear. Currently we ensure that all esophagectomy patients have a CT scan within the first year postop. We recommend repair of HHBPE in patients with severe or progressive symptoms. Most of the time HHBPE follows a benign course and does not require operation. All patients with HHBPE are followed indefinitely. A prospective randomized trial of conduit fixation to the crural diaphragm in patients undergoing transhiatal esophagectomy should be considered.
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REFERENCES 1) Oor JE, Wiezer MJ, Hazebroek EJ. Hiatal Hernia after Open versus Minimally Invasive Esophagectomy: A Systematic Review and Meta-analysis. Ann Surg Oncol 2016; 23:269098. doi: 10.1245/s10434-016-5155-x 2) Kent MS, Luketich JD, Tsai W, et al. Revisional surgery after esophagectomy: an analysis of 43 patients. Ann Thorac Surg 2008; 86:975-983. doi: 10.1016/j.athoracsur.2008.04.098 3) Price, T. N., Allen, M. S., Nichols, F. C., et al. Hiatal Hernia After Esophagectomy: Analysis of 2,182 Esophagectomies From a Single Institution. The Ann Thorac Surg 2011; 92(6), 2041-45. doi: 10.1016/j.athoracsur.2011.08.013 4) Ganeshan DM, Correa AM, Bhosale P, et al. Diaphragmatic Hernia After Esophagectomy in 440 Patients With Long-Term Follow-Up. Ann Thorac Surg 2013; 96:1138–45. doi: 10.1016/j.athoracsur.2013.04.076 5) Bronson NW, Luna RA, Hunter JG, and Dolan JP. The incidence of Hiatal Hernia after Minimally Invasive Esophagectomy. J Gastrointest Surg 2014; 18:889-93. doi: 10.1007/s11605-014-2481-9 6) Crespin OM, Farjah F, Cuevas C, et al. Hiatal Herniation After Transhiatal Esophagectomy: An Underreported Complication. J Gastrointest Surg 2016; 20:231–236. doi: 10.1007/s11605-015-3033-7 7) Brenkman HJ, Parry K, Noble F, et al. Hiatal Hernia After Esophagectomy for Cancer. Ann Thorac Surg 2017; 103:1055–62. doi: 10.1016/j.athoracsur.2017.01.026 8) Severino BU, Fuks D, Christidis C, et al: Laparoscopic repair of hiatal hernia after minimally invasive esophagectomy. Surg Endosc 2016; 30:1068-1072. doi: 10.1007/s00464-015-4299-2
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9) Ferlay J, Soerjomataram I, Ervik, M, et al. GLOBOCAN 2012v1.0, Cancer Incidence and Mortality Worldwide. IARC Cancer Base No. 11. Lyon, France: International Agency for Research on Cancer 2013. doi: 10.1002/ijc.29210 10) Wong, MC, Hamilton W, Whiteman, et al. Global Incidence and mortality of oesophageal cancer and their correlation with socioeconomic indicators temporal patterns and trends in 41 countries. Scientific Reports 2018; 8(1). doi:10.1038/s41598-018-19819-8 11) Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet 2013; 381, 400–412. doi: 10.1016/S0140-6736(12)60643-6 12) Mao WM, Zheng WH, Long, ZQ. Epidemiologic risk factors for esophageal cancer development. Asian Pac J Cancer Prev 2011; 12, 2461–2466. doi: 10.3748/wjg.v19.i34.5598 13) Tepper JE, O’Neil B. Transition in biology and philosophy in the treatment of gastroesophageal junction adenocarcinoma. J Clin Oncol 2009; 27(6):836. doi: 10.1200/JCO.2008.19.5982 14) Shapiro J, Lanschot JJ, Hulshof MC, Hagen, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Onc 2015; 16(9), 1090-1098. doi: 10.1016/S1470-2045(15)00040-6 15) Gooszen JAH, Slaman AE, van Dieren S, et al. Incidence and Treatment of Symptomatic Diaphragmatic Hernia After Esophagectomy. Ann Thorac Surg 2018; 106:199–206. doi: 10.1016/j.athoracsur.2018.02.034 16) Benjamin G, Ashfaq A, Chang YH, et al. Diaphragmatic hernia post-minimally invasive esophagectomy: a discussion and review of the literature. Hernia 2015; 19:635-43. doi: 10.1007/s10029-015-1363-8
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17) Narayanan S, Sanders RL, Herlitz G, et al. Treatment of Diaphragmatic Hernia Occurring After Transhiatal Esophagectomy. Ann Surg Oncol 2015 Oct;22(11):3681-6. doi: 10.1245/s10434-015-4366-x 18) Sutherland J, Banerji N, Morphew J, et al. Postoperative incidence of incarcerated hiatal hernia and its prevention after robotic transhiatal esophagectomy. Surg Endosc.2011 May;25(5):1526-30. doi: 10.1007/s00464-010-1429-8 19) Willer BL, Worrell SG, Fitzgibbons RJ, Mittal SK. Incidence of diaphragmatic hernias following minimally invasive versus open transthoracic Ivor Lewis McKeown esophagectomy. Hernia 2012; 16:185-190. doi: 10.1007/s10029-011-0884-z 20) Messenger DE, Higgs SM, Dwerryhouse SJ, et al. Symptomatic diaphragmatic herniation following open and minimally invasive oesophagectomy: experience from a UK specialist unit. Surg Endosc 2015 Feb;29(2):417-24. doi: 10.1007/s00464-014-3689-1 21) Matthews J, Bhanderi S, Mitchell H, et. al. Diaphragmatic herniation following esophagogastric resectional surgery: an increasing problem with minimally invasive techniques? Surg Endosc 2016; 30:5419-27. doi: 10.1007/s00464-016-4899-5 22) Orringer MB. Transhiatal esophagectomy: how I teach it. Ann Thorac Surg 2016; 102:14321437. doi: 10.1016/j.athoracsur.2016.09.044
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Table 1. Baseline Patient Characteristics Variable
No HHBPE (n = 179) 145 (81) 63.5
HHBPE (n = 79) 66 (84) 62.4
p Value
Male, n (%) 0.73 Mean age, y 0.38 Pre-procedure BMI, n (%) 0.51 < 18.5 53 (30) 23 (29) 18.5 to 24.9 70 (39) 25 (32) 25 to 29.9 50 (28) 29 (37) ≥ 30 6 (3) 2 (2) Smoker, n (%) 135 (75) 54 (68) 0.29 Neoadjuvant therapy, n (%) 114 (64) 62 (78) 0.02 Neoplastic pathology, n (%) 172 (96) 75 (96) 0.74 Site of cancer, n (%) 0.46 Upper third 1 (1) 0 (0) Middle third 7 (4) 2 (3) Lower third 20 (11) 4 (5) Gastroesophageal junction 144 (80) 69 (87) NA* 7 (4) 4 (5) Clinical T Stage: T0 or T1, n (%) 57 (33) 11 (15) 0.003 Nodal disease, n (%) 80 (45) 46 (58) 0.04 Clinical stage > II, n (%) 117 (65) 63 (80) 0.01 Preop hiatal hernia, n (%) 61 (34) 23 (30) 0.47 MIS, n (%) 95 (53) 59 (75) 0.001 Surgery type, n (%) < 0.001 Ivor-Lewis 46 (26) 6 (8) McKeown 14 (8) 3 (4) Transhiatal 119 (66) 70 (88) Adjuvant therapy, n (%) 61 (34) 27 (34) 1.0 Follow up, months, median (IQR) 22.7 (16 – 36) 31.2 (21 – 44) 0.002 *Patients who underwent esophagectomy for benign indication HHBPE, hiatal herniation of bowel post esophagectomy; MIS, minimally invasive surgery; IQR, inter-quartile range; NA, not applicable
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Table 2. Multivariate Predictors of Hiatal Herniation of Bowel Post Esophagectomy Full model Variable
Odds ratio
95% CI
Reduced model p Value
Odds ratio
95% CI
p Value
Sex Female Reference N/A N/A Male 1.22 0.54 – 2.75 0.63 Age, 10 y 0.95 0.70 – 1.34 0.74 Pre-procedure BMI, 1.14 0.95 - 1.31 0.21 kg/m2 < 18.5 Reference N/A N/A 18.5 to 24.9 0.99 0.16 – 6.1 0.99 25 to 29.9 0.57 0.28 – 1.2 0.14 ≥ 30 1.12 0.55 – 2.4 0.71 Smoker 0.68 0.28 - 1.71 0.42 Neoadjuvant therapy 1.61 1.09 – 2.44 0.04 2.14 1.17 – 3.94 0.01 Nodal disease 0.95 0.45 – 2.0 0.89 Preop hiatal hernia 1.93 0.99 – 3.78 0.06 MIS 1.48 0.74 - 2.99 0.27 Transhiatal approach 3.1 1.27 – 7.43 0.01 3.4 1.61 – 7.27 0.001 HHBPE, hiatal herniation of bowel post esophagectomy; MIS, minimally invasive surgery; N/A, not applicable
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Table 3. Patients Undergoing Repair of Hiatal Herniation of Bowel Post Esophagectomy Patient
Months after esophagectomy
Elective?
Hernia content
Repair type
Recurred?
1
<1
No
Colon
Primary
No
2
6
No
Small bowel
Mesh
No
3
3
No
Small bowel
Mesh
Yes
4
14
No
Small bowel
Primary
No
5
23
Yes
Small bowel and colon
Primary
Yes
6
9
Yes
Colon
Primary
No
7
<1
No
Small bowel
Mesh
No
8
21
Yes
Small bowel
Primary
Yes
9
10
Yes
Primary
No
10
39
Yes
Primary
No
11
23
No
Small bowel
Primary
Yes
12
12
Yes
Colon
Primary
No
13
11
Yes
Colon
Primary
No
14
7
No
Small bowel
Primary
No
15
5
No
Small bowel
Primary
Yes
16
18
Yes
Small bowel and colon
Primary
No
17
19
Yes
Small bowel
Primary
No
Small bowel and colon Small bowel and colon
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Table 4. Literature Describing Hiatal Hernia after Esophagectomy Study Price et al, 2011 Gooszen et al, 2018 Benjamin et al, 2015 Narayanan et al, 2015 Sutherland et al, 2011 Brenkman et al, 2017 Severino et al, 2016 Ganeshan et al, 2013 Messenger et al, 2015 Bronson et al, 2014 Crespin et al, 2016 Kent et al, 2008 Willer et al, 2012 Current study, 2020
Interval, y
Total esophagectomies
Patients in study, n
Follow-up months, median
Minimally invasive, %
THE, %
Crural fixation
Neoadjuvant therapy, %
Routine imaging
21
2182
2182
23
Unknown
Unknow n
Unknown
Unknown
No
11
851
851
Unknown
41
27
Some
62
No
7
Unknown
120
26
100
0
Unknown
71
Yes
13.5
199
199
26
Unknown
98
Unknown
54
Yes
2
Unknown
36*
Unknown
100
100
Unknown
44
No
14
657
488
18
66
17
No
66
Yes
13.4
390
390
Unknown
100
0
No
Unknown
No
7
554
440
52
7
23
Some
Unknown
Yes
16
273
273
Unknown
25
15
Some
62
No
8
Unknown
114
Unknown
100
94
Yes
Unknown
Yes
9
Unknown
192
8
100
100
Yes
67
Yes
12
1075
1075
Unknown
54
0
Yes
Unknown
No
6
133
39†
Unknown
49
0
Yes
69
Yes
6.5
310
258
24
60
73
No
68
Yes
3
* all esophagectomies performed robotically † all esophagectomies performed using Mckeown approach THE, transhiatal esophagectomy
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Table 5. Results from Prior Literature Describing Hiatal Hernia after Esophagectomy
Study
Price et al, 2011 Gooszen et al, 2018 Benjamin et al, 2015 Narayanan et al, 2015 Sutherland et al, 2011 Brenkman et al, 2017 Severino et al, 2016 Ganeshan et al, 2013 Messenger et al, 2015 Bronson et al, 2014 Crespin et al, 2016 Kent et al,
HH, postesophagectomy, n
Time to HH diagnosis, months, median
Symptomatic HH, n
HH repaired, n
HH mortality, n
HH requiring bowel resection, n
HH recurrence, n
Multivariable predictors of post esophagectomy HH
HH, n
15
21
15
13
15
0
2
2
NA
21
6
Unknown
21
21
1
Unknown
4
MIS; Ivor-Lewis
7
Unknown
7
5
6
0
0
1
NA
10
29
10
10
10
0
0
0
NA
7
Unknown
Unknown
7
7
1
3
Unknown
NA
45
20
Unknown
31
45
3
Unknown
4
BMI < 25
32
10
Unknown
22
32
0
1
6
NA
67
Unknown
33
8
9
1
Unknown
4
Male; BMI < 25; THE
11
Unknown
11
11
11
0
0
2
NA
9
14†
8
4
11*
0
1
3*
NA
22
Unknown
Unknown
7
7
0
0
1
NA
24
32†
24
20
22
1
Unknown
6
NA
3
2008 Willer et al, 2012 Current Study, 2020
5
14 †
4
0
3
Unknown
0
Unknown
NA
79
31
79
44
17
0
0
5
THE, NAT
* one patient had 2 recurrences † mean HH, hiatal hernia; NA, not analyzed; MIS, minimally invasive surgery; THE, transhiatal esophagectomy; NAT, neoadjuvant therapy
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Figure Legend Figure 1. Comparing rates of hiatal herniation of small and/or large bowel post esophagectomy (HHBPE) in patients who satisfied both, only one, or none of the two significant predictors of HHBPE: neoadjuvant therapy and a transhiatal approach Figure 2. An example of hiatal herniation of colon into the left thorax post esophagectomy. Patient had primary repair of hiatal herniation of small and/or large bowel post esophagectomy and has not recurred.
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Precis Hiatal hernia after esophagectomy is an increasingly recognized complication that can be seen weeks or years post-resection. Transhiatal approach and neoadjuvant therapy are significant risk factors for this complication. While most patients follow a benign course, some will develop severe symptoms that require surgical intervention.
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S1072-7515(20)30070-3
DOI:
https://doi.org/10.1016/j.jamcollsurg.2019.12.009
Reference:
ACS 9702
To appear in:
Journal of the American College of Surgeons
Received Date: 16 December 2019 Accepted Date: 16 December 2019
Please cite this article as: Hanna AN, Guajardo I, Williams N, Kucharczuk J, Dempsey DT, Hiatal Hernia after Esophagectomy: An Underappreciated Complication?, Journal of the American College of Surgeons (2020), doi: https://doi.org/10.1016/j.jamcollsurg.2019.12.009. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc. on behalf of the American College of Surgeons.
Hiatal Hernia after Esophagectomy: An Underappreciated Complication? Andrew N Hanna, MD1, Isabella Guajardo, MD2, Noel Williams, MD1, John Kucharczuk, MD, FACS1, Daniel T Dempsey, MD, MBA, FACS1 1 2
Department of Surgery, University of Pennsylvania, Philadelphia, PA Department of Surgery, UC San Diego, San Diego, CA
Disclosure Information: Nothing to disclose. Presented at the Southern Surgical Association 129th Annual Meeting, Hot Springs, VA, December 2019. Corresponding Author: Daniel T Dempsey, MD Professor of Surgery University of Pennsylvania 3400 Spruce Street Philadelphia, PA 19104 Tel: 215-614-0092 Email: [email protected]
Brief Title: Hiatal Hernia after Esophagectomy
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Background: The natural history of hiatal herniation of small and/or large bowel post esophagectomy (HHBPE), in the current era of improving long term survival and evolving surgical technique, is unknown. The aim of this study is to describe the rate and risk factors of HHBPE at our hospital. Methods: Patients undergoing esophagectomy between January, 2011 and June, 2017 were included if both follow up information and axial imaging were available beyond 3 months post esophagectomy. Patient characteristics, disease information, and treatment factors were all included in univariate analysis comparing patients with and without HHBPE, and multivariate regression was used to identify significant independent risk factors associated with HHBPE. Results: Out of 310 esophagectomy patients analyzed, 258 patients were included in the study, with 79 patients (31%) showing evidence of a HHBPE and an overall median follow-up of 24 months; 44/79 (56%) had symptoms possibly referable to HHBPE and 17/79 (22%) underwent surgical repair. On univariate analysis, neoadjuvant therapy (n = 176), higher clinical stage, minimally invasive approach (n = 154), and transhiatal esophagectomy (n = 189) were significant predictors of HHBPE (p<0.05). On multivariate analysis, neoadjuvant therapy and transhiatal approach remained significant independent predictors (p < 0.05). In the 131 patients (51%) that had both factors, the rate of HHBPE was 44%. Conclusions: HHBPE in the current era of neoadjuvant therapy and minimally invasive esophagectomy is common. HHBPE may cause GI symptoms but operation to repair HHBPE is uncommon on intermediate follow up. Further study and long-term follow are required to fully assess the impact of HHBPE and to potentially modify surgical practice to prevent or minimize HHBPE. Keywords: hiatal hernia, esophagectomy, risk factors
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INTRODUCTION Hiatal herniation of small and/or large intestine is a recognized complication of esophagectomy, an operation that disrupts the phrenoesophageal ligament and dilates the hiatus. The natural history of this complication is unclear. A review of the literature revealed a limited number of studies that reported an estimated incidence range of 0.4 to 19.4% (1). These studies also compared different surgical approaches and had a wide range of follow-up intervals. Some authors suggest that hiatal herniation of bowel after esophagectomy is an unusual complication, while others suggest that it is quite common. Furthermore, some authors suggest that bowel herniated through the hiatus after esophagectomy is in danger of strangulation and should be operated upon when diagnosed, while others suggest observation is appropriate for the majority of patients with this finding unless worrisome symptoms ensue (2 - 6). Hiatal herniation of fat after esophagectomy is probably both common and trivial, and the significance of herniation of solid organs is unknown. Repair of hiatal herniation after esophagectomy can be challenging and morbid, and recurrent herniation is common. It may be difficult to prevent hiatal herniation after esophagectomy, but some authors favor routine suturing of the esophageal replacement conduit (usually stomach) to the crural diaphragm (5,6). Other surgeons do this rarely if at all (7,8). It may be worthwhile identifying predictive factors for hiatal herniation of small and/or large bowel post esophagectomy (HHBPE) so that in patients at risk preventive measures may be attempted during esophagectomy and/or closer postoperative follow up may be employed. Hiatal herniation of bowel after esophagectomy is likely to be seen more commonly now because esophagectomy is performed with both increased frequency and increased long term survival (914). Patient survival after esophagectomy has improved overall due to advancements in cancer
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therapeutics and surgical technology. As more patients treated for esophageal cancer survive, the number of patients facing treatment complications will increase. Furthermore, both minimally invasive techniques and transhiatal esophagectomy without thoracotomy are now more often employed for esophagectomy than in the past, and both these factors have been associated with increased risk of post esophagectomy hiatal hernia in some studies. Although post-esophagectomy hiatal hernias were previously reported to occur in the acute post-operative setting, they have recently been found months to years after the initial procedure. Thus it is important for surgeons, oncologists, gastroenterologists, and radiologists to understand the clinical significance of HHBPE. Since 2011, our 3 surgeon team has performed 90% of the esophagectomies in our health system using a standard technique for both open and laparoscopic assisted operations. The purpose of our study was to define the natural history and risk factors for HHBPE, hoping to minimize the confounding effects, seen in some studies, of multiple surgeons using evolving techniques over many years. METHODS All patients undergoing esophagectomy between January 1, 2011 and June 30, 2017 were included in this retrospective analysis with institutional review board approval. Data recorded included age, gender, BMI, smoking history, indication for operation, clinical tumor stage on presentation and neoadjuvant treatment information for cancer patients, date of operation, operating surgeon(s), postoperative imaging results, reoperation for hiatal hernia, and postoperative clinic visit results. All available relevant preoperative and postoperative imaging studies (CT, MRI, CXR) and reports were reviewed for the presence of hiatal herniation of bowel.
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Patients were excluded from study if there was no available imaging beyond 3 months post esophagectomy, but we did not knowingly exclude any patient with early HHBPE. Univariate analysis was used to compare patients with and without HHBPE, and multivariate regression analysis was used to identify significant factors associated with the development of HHBPE. Frequency tables were used to describe discrete variables, with continuous variables described with mean values or normally distributed values and median/interquartile ranges for non-normally distributed variables. Comparisons between patients were performed using MannWhitney U tests for continuous data and Fisher exact tests for discrete variables. Multivariate logistic regression was then used to determine predictors of HHBPE and significant factors of the reduced model were then used to assess the risk of HHBPE in the study cohort. All statistical analyses were performed using R: A Language and Environment for Statistical Computing (Vienna, Austria). RESULTS During the study period, esophagectomy was performed in 310 patients. Fifty-two patients were excluded because of lack of imaging studies beyond 3 months. Thus, 258 patients met entry criteria and were followed for a median of 24 months (IQR, 18 months – 30 months). In the study group of 258 patients the following esophagectomy approaches were used: open Ivor Lewis (n = 46); laparoscopic assisted Ivor Lewis (n = 6); open transhiatal (n = 47); laparoscopic assisted transhiatal (n = 142); open “3 hole” McKeown (n = 11); laparoscopic assisted “3 hole” McKeown (n = 6). The incidence of HHBPE of the entire cohort was 31% (79/258). Patients with HHBPE had a median follow-up of 31.2 months compared with a median follow-up of 22.7 months in patients without HHBPE (p=0.002). All patient characteristics are summarized in Table 1.
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On univariate analysis, the following factors were significantly associated with HHBPE: neoadjuvant chemoradiation (n = 176); laparoscopic assisted technique (n = 154); transhiatal approach (n = 189); and higher clinical stage at presentation. The following factors were not significantly associated with HHBPE on univariate analysis: age, BMI, smoking history, gender, preoperative hiatal hernia, and indication for esophagectomy. On multivariate analysis, shown in Table 2, neoadjuvant treatment and transhiatal approach were significant independent predictors of HHBPE and remained significant on the reduced multivariate regression model. In patients where both factors were present (n=131), HHBPE developed in 58 patients (44%). When no factor or only 1 factor was present, HHBPE developed in 19 (20%) and 3 (10%) patients respectively (Figure 1). Forty-four of the 79 patients with HHBPE (56%) had symptoms possibly caused by the hiatal herniation. Seventeen of these 79 patients (22%) underwent surgical repair of HHBPE, including two patients in the first month postesophagectomy, with no mortality and no bowel resections required. Out of these 17 patients, 5 eventually recurred with 1 requiring an emergent repair. Table 3 describes in detail the outcomes of these 17 patients. Figure 2 shows a representative cross-sectional coronal image of one of these patients with a significant hiatal hernia 3 years after esophagectomy who eventually underwent primary repair with no evidence of recurrence since. DISCUSSION In this analysis of 258 esophagectomy patients with postoperative imaging studies followed for a median of 24 months, we found radiologic evidence of postoperative hiatal herniation of bowel in 79 patients (31%). Over half (56%) of these 79 patients were deemed by
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the surgeon on follow up to have symptoms possibly related to HHBPE, but only 17 of the 44 symptomatic patients (39%) required operation to repair HHBPE. Many patients with HHBPE had mild symptoms, or symptoms that were questionably related to the postoperative hiatal hernia. Thus only 7% of the study population (17/258), and only 22% of patients with HHBPE (17/79) required operation on follow up. There were no deaths related to HHBPE and no bowel resections related to HHBPE. Both preoperative neoadjuvant chemoradiation, and transhiatal without thoracotomy approach (but not laparoscopic assisted operation), were independently associated with increased likelihood of HHBPE. Based on these findings we do not recommend operation for HHBPE unless symptoms are severe or progressive. We do however follow patients indefinitely if they are found to have HHBPE, or if they have had a transhiatal esophagectomy without thoracotomy, or if they have received neoadjuvant treatment. This constitutes the majority of our esophagectomy population, all of whom have CT scan of chest and abdomen within the first year post esophagectomy. Follow up includes patient and family education about symptoms which may indicate incarceration or strangulation of herniated transhiatal intestine. The incidence of HHBPE found in our study is higher than any published series, as summarized in Table 4 and Table 5 (2-8,15-20). Though our follow up is longer than some studies, this is probably not a major reason for this finding. Our higher incidence of HHBPE is likely due to several factors. Firstly, we looked for HHBPE in every patient included in our series with postoperative imaging and if imaging findings were equivocal for HHBPE, we considered the patients to have had HHBPE. Analysis of published studies clearly shows that the occurrence of postesophagectomy hiatal hernia is significantly more common in studies that utilized and scrutinized postop imaging in the study population. As with so many things in
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surgery, if you do not look for it you will not find it. For example, Price et al reported on 15 patients reoperated on at the Mayo Clinic for hiatal herniation of abdominal contents at a median of 1.75 years after esophagectomy at that facility (4). These patients were accumulated over many years, and represented only 0.69% of the 2,182 esophagectomies performed during that time at Mayo Rochester, most of which were Ivor Lewis operations. While the authors concluded that HHBPE is unusual, the lack of routine imaging makes this conclusion suspect and an incidence of less than 1% is likely a substantial underestimation of the true incidence of HHBPE. Similarly, Kent et al from Pittsburgh reported a 2% incidence of HHBPE in 1075 patients without routine review of postop imaging (2). Other large series which included postoperative imaging show a much higher likelihood of post esophagectomy hiatal herniation. Ganeshan et al from MD Anderson reported 67 diaphragmatic hernias (67/440=15%) at a median 2 years after esophagectomy; there were 33 patients with HHBPE (33/440=7.5%). (4) At a median follow up of 8 months, Crespin et al at the University of Washington found postoperative hiatal herniation in 22 of 192 esophagectomy patients (22/192=11%) (6). Similarly, from Europe Brenkman et al reported 45 postoperative hiatal hernias in 488 esophagectomy patients followed for a median of 18 months (45/488=9%) (7). These studies which look for HHBPE with postoperative imaging identify this complication much more commonly than those which rely on symptoms. This observation is consistent with our belief that most patients with HHBPE have minimal symptoms. Secondly, most of the patients in our series were treated with transhiatal esophagectomy and a laparoscopic assisted approach. It has been suggested in the literature that both factors increase the likelihood of HHBPE. Gooszen et al from Amsterdam applied multivariate analysis to a large series of patients (n=851) and found that minimally invasive Ivor Lewis was associated
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with increased risk of HHBPE (15). Matthews et al from UK found significantly more postoperative hiatal hernias in patients having minimally invasive esophagectomy (27/285=10%) compared to those having an open operation (4/221=2%) (21). However, on multivariate analysis, the minimally invasive approach was not a significant predictor of HHBPE in our study. When comparing publications where most of the esophagectomies were done minimally invasively to those where most were done open, the incidence of HHBPE is about the same. Whether a minimally invasive approach conclusively increases the risk of hiatal hernia is still therefore open to debate. We think that the data favoring transhiatal resection without thoracotomy as a risk factor for HHBPE is much stronger. In the current series it was by far the strongest risk factor. Ganeshan et al also found that transhiatal esophagectomy was a significant risk factor in their study population of 440 patients (4). Also when the literature is scrutinized, publications where transhiatal esophagectomy is performed most commonly have a higher incidence of HHBPE than those that use the transhiatal approach less frequently. It is likely that our heavy reliance on transhiatal esophagectomy without thoracotomy, and perhaps our now routine use of a laparoscopic assisted approach, contributed substantially to our high incidence of HHBPE. We also noted a significantly higher rate of HHBPE in patients treated with neoadjuvant chemoradiation, a significant risk factor on multivariate analysis. It is possible that chemoradiation slows the development of postoperative adhesions and favors transhiatal migration of bowel into the chest and mediastinum. It is also possible that it defines more advanced tumor stage requiring more substantial perihiatal resection which favors postoperative herniation.
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Finally, there are undoubtedly technical factors associated with HHBPE but many of these are hard to measure. We do not routinely suture the conduit to the crural diaphragm nor do we routinely attempt to reconstruct the crura. While some surgeons maintain that these are important steps to prevent hiatal herniation after esophagectomy, conclusive evidence in this regard is wanting. Orringer routinely sutures the gastric conduit to the crural diaphragm (22). Careful review of the literature suggests that the incidence of HHBPE is about the same whether or not the conduit is sutured to the crural diaphragm. Brenkman et al and Severino et al in two European series with good imaging follow up specifically state that surgeons do not fix the conduit to the diaphragm, and they report an incidence of HHBPE of 9% and 8% respectively (7, 8). In the US, Bronson et al from OHSU and Crespin et al from University of Washington report HHBPE in 8% and 11% of their patients, respectively, when the conduit is routinely sutured to the crura (5,6). Thus it is not clear whether the lack of crural fixation contributed to our high rate of HHBPE. Our experience and review of the literature suggest that HHBPE is usually not dangerous. Many patients with this complication have minimal symptoms. In the absence of worsening symptoms, the risk of bowel strangulation is very low, quite analogous to paraesophageal hernia (PEH). We had no deaths or bowel strangulation in our series. Perusal of the articles summarized in Table 4 and Table 5 shows only seven deaths and seven bowel resections related to HHBPE out of thousands of esophagectomy patients. Recurrence after repair is quite common (also analogous to PEH). Injudicious repair of asymptomatic HHPBE should be avoided. CONCLUSIONS We found HHBPE in 31% of our current series of esophagectomy patients. Transhiatal resection and preoperative chemoradiation were significant risk factors for HHBPE on
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multivariate analysis, and the fact that the majority of our patients had both factors may have contributed to our high incidence of postoperative herniation. Whether the now routine use of the laparoscopic assisted approach and/or the lack of fixation of the conduit to the crura increased the risk of postoperative herniation in our series is unclear. Currently we ensure that all esophagectomy patients have a CT scan within the first year postop. We recommend repair of HHBPE in patients with severe or progressive symptoms. Most of the time HHBPE follows a benign course and does not require operation. All patients with HHBPE are followed indefinitely. A prospective randomized trial of conduit fixation to the crural diaphragm in patients undergoing transhiatal esophagectomy should be considered.
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REFERENCES 1) Oor JE, Wiezer MJ, Hazebroek EJ. Hiatal Hernia after Open versus Minimally Invasive Esophagectomy: A Systematic Review and Meta-analysis. Ann Surg Oncol 2016; 23:269098. doi: 10.1245/s10434-016-5155-x 2) Kent MS, Luketich JD, Tsai W, et al. Revisional surgery after esophagectomy: an analysis of 43 patients. Ann Thorac Surg 2008; 86:975-983. doi: 10.1016/j.athoracsur.2008.04.098 3) Price, T. N., Allen, M. S., Nichols, F. C., et al. Hiatal Hernia After Esophagectomy: Analysis of 2,182 Esophagectomies From a Single Institution. The Ann Thorac Surg 2011; 92(6), 2041-45. doi: 10.1016/j.athoracsur.2011.08.013 4) Ganeshan DM, Correa AM, Bhosale P, et al. Diaphragmatic Hernia After Esophagectomy in 440 Patients With Long-Term Follow-Up. Ann Thorac Surg 2013; 96:1138–45. doi: 10.1016/j.athoracsur.2013.04.076 5) Bronson NW, Luna RA, Hunter JG, and Dolan JP. The incidence of Hiatal Hernia after Minimally Invasive Esophagectomy. J Gastrointest Surg 2014; 18:889-93. doi: 10.1007/s11605-014-2481-9 6) Crespin OM, Farjah F, Cuevas C, et al. Hiatal Herniation After Transhiatal Esophagectomy: An Underreported Complication. J Gastrointest Surg 2016; 20:231–236. doi: 10.1007/s11605-015-3033-7 7) Brenkman HJ, Parry K, Noble F, et al. Hiatal Hernia After Esophagectomy for Cancer. Ann Thorac Surg 2017; 103:1055–62. doi: 10.1016/j.athoracsur.2017.01.026 8) Severino BU, Fuks D, Christidis C, et al: Laparoscopic repair of hiatal hernia after minimally invasive esophagectomy. Surg Endosc 2016; 30:1068-1072. doi: 10.1007/s00464-015-4299-2
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9) Ferlay J, Soerjomataram I, Ervik, M, et al. GLOBOCAN 2012v1.0, Cancer Incidence and Mortality Worldwide. IARC Cancer Base No. 11. Lyon, France: International Agency for Research on Cancer 2013. doi: 10.1002/ijc.29210 10) Wong, MC, Hamilton W, Whiteman, et al. Global Incidence and mortality of oesophageal cancer and their correlation with socioeconomic indicators temporal patterns and trends in 41 countries. Scientific Reports 2018; 8(1). doi:10.1038/s41598-018-19819-8 11) Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet 2013; 381, 400–412. doi: 10.1016/S0140-6736(12)60643-6 12) Mao WM, Zheng WH, Long, ZQ. Epidemiologic risk factors for esophageal cancer development. Asian Pac J Cancer Prev 2011; 12, 2461–2466. doi: 10.3748/wjg.v19.i34.5598 13) Tepper JE, O’Neil B. Transition in biology and philosophy in the treatment of gastroesophageal junction adenocarcinoma. J Clin Oncol 2009; 27(6):836. doi: 10.1200/JCO.2008.19.5982 14) Shapiro J, Lanschot JJ, Hulshof MC, Hagen, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Onc 2015; 16(9), 1090-1098. doi: 10.1016/S1470-2045(15)00040-6 15) Gooszen JAH, Slaman AE, van Dieren S, et al. Incidence and Treatment of Symptomatic Diaphragmatic Hernia After Esophagectomy. Ann Thorac Surg 2018; 106:199–206. doi: 10.1016/j.athoracsur.2018.02.034 16) Benjamin G, Ashfaq A, Chang YH, et al. Diaphragmatic hernia post-minimally invasive esophagectomy: a discussion and review of the literature. Hernia 2015; 19:635-43. doi: 10.1007/s10029-015-1363-8
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17) Narayanan S, Sanders RL, Herlitz G, et al. Treatment of Diaphragmatic Hernia Occurring After Transhiatal Esophagectomy. Ann Surg Oncol 2015 Oct;22(11):3681-6. doi: 10.1245/s10434-015-4366-x 18) Sutherland J, Banerji N, Morphew J, et al. Postoperative incidence of incarcerated hiatal hernia and its prevention after robotic transhiatal esophagectomy. Surg Endosc.2011 May;25(5):1526-30. doi: 10.1007/s00464-010-1429-8 19) Willer BL, Worrell SG, Fitzgibbons RJ, Mittal SK. Incidence of diaphragmatic hernias following minimally invasive versus open transthoracic Ivor Lewis McKeown esophagectomy. Hernia 2012; 16:185-190. doi: 10.1007/s10029-011-0884-z 20) Messenger DE, Higgs SM, Dwerryhouse SJ, et al. Symptomatic diaphragmatic herniation following open and minimally invasive oesophagectomy: experience from a UK specialist unit. Surg Endosc 2015 Feb;29(2):417-24. doi: 10.1007/s00464-014-3689-1 21) Matthews J, Bhanderi S, Mitchell H, et. al. Diaphragmatic herniation following esophagogastric resectional surgery: an increasing problem with minimally invasive techniques? Surg Endosc 2016; 30:5419-27. doi: 10.1007/s00464-016-4899-5 22) Orringer MB. Transhiatal esophagectomy: how I teach it. Ann Thorac Surg 2016; 102:14321437. doi: 10.1016/j.athoracsur.2016.09.044
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Table 1. Baseline Patient Characteristics Variable
No HHBPE (n = 179) 145 (81) 63.5
HHBPE (n = 79) 66 (84) 62.4
p Value
Male, n (%) 0.73 Mean age, y 0.38 Pre-procedure BMI, n (%) 0.51 < 18.5 53 (30) 23 (29) 18.5 to 24.9 70 (39) 25 (32) 25 to 29.9 50 (28) 29 (37) ≥ 30 6 (3) 2 (2) Smoker, n (%) 135 (75) 54 (68) 0.29 Neoadjuvant therapy, n (%) 114 (64) 62 (78) 0.02 Neoplastic pathology, n (%) 172 (96) 75 (96) 0.74 Site of cancer, n (%) 0.46 Upper third 1 (1) 0 (0) Middle third 7 (4) 2 (3) Lower third 20 (11) 4 (5) Gastroesophageal junction 144 (80) 69 (87) NA* 7 (4) 4 (5) Clinical T Stage: T0 or T1, n (%) 57 (33) 11 (15) 0.003 Nodal disease, n (%) 80 (45) 46 (58) 0.04 Clinical stage > II, n (%) 117 (65) 63 (80) 0.01 Preop hiatal hernia, n (%) 61 (34) 23 (30) 0.47 MIS, n (%) 95 (53) 59 (75) 0.001 Surgery type, n (%) < 0.001 Ivor-Lewis 46 (26) 6 (8) McKeown 14 (8) 3 (4) Transhiatal 119 (66) 70 (88) Adjuvant therapy, n (%) 61 (34) 27 (34) 1.0 Follow up, months, median (IQR) 22.7 (16 – 36) 31.2 (21 – 44) 0.002 *Patients who underwent esophagectomy for benign indication HHBPE, hiatal herniation of bowel post esophagectomy; MIS, minimally invasive surgery; IQR, inter-quartile range; NA, not applicable
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Table 2. Multivariate Predictors of Hiatal Herniation of Bowel Post Esophagectomy Full model Variable
Odds ratio
95% CI
Reduced model p Value
Odds ratio
95% CI
p Value
Sex Female Reference N/A N/A Male 1.22 0.54 – 2.75 0.63 Age, 10 y 0.95 0.70 – 1.34 0.74 Pre-procedure BMI, 1.14 0.95 - 1.31 0.21 kg/m2 < 18.5 Reference N/A N/A 18.5 to 24.9 0.99 0.16 – 6.1 0.99 25 to 29.9 0.57 0.28 – 1.2 0.14 ≥ 30 1.12 0.55 – 2.4 0.71 Smoker 0.68 0.28 - 1.71 0.42 Neoadjuvant therapy 1.61 1.09 – 2.44 0.04 2.14 1.17 – 3.94 0.01 Nodal disease 0.95 0.45 – 2.0 0.89 Preop hiatal hernia 1.93 0.99 – 3.78 0.06 MIS 1.48 0.74 - 2.99 0.27 Transhiatal approach 3.1 1.27 – 7.43 0.01 3.4 1.61 – 7.27 0.001 HHBPE, hiatal herniation of bowel post esophagectomy; MIS, minimally invasive surgery; N/A, not applicable
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Table 3. Patients Undergoing Repair of Hiatal Herniation of Bowel Post Esophagectomy Patient
Months after esophagectomy
Elective?
Hernia content
Repair type
Recurred?
1
<1
No
Colon
Primary
No
2
6
No
Small bowel
Mesh
No
3
3
No
Small bowel
Mesh
Yes
4
14
No
Small bowel
Primary
No
5
23
Yes
Small bowel and colon
Primary
Yes
6
9
Yes
Colon
Primary
No
7
<1
No
Small bowel
Mesh
No
8
21
Yes
Small bowel
Primary
Yes
9
10
Yes
Primary
No
10
39
Yes
Primary
No
11
23
No
Small bowel
Primary
Yes
12
12
Yes
Colon
Primary
No
13
11
Yes
Colon
Primary
No
14
7
No
Small bowel
Primary
No
15
5
No
Small bowel
Primary
Yes
16
18
Yes
Small bowel and colon
Primary
No
17
19
Yes
Small bowel
Primary
No
Small bowel and colon Small bowel and colon
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Table 4. Literature Describing Hiatal Hernia after Esophagectomy Study Price et al, 2011 Gooszen et al, 2018 Benjamin et al, 2015 Narayanan et al, 2015 Sutherland et al, 2011 Brenkman et al, 2017 Severino et al, 2016 Ganeshan et al, 2013 Messenger et al, 2015 Bronson et al, 2014 Crespin et al, 2016 Kent et al, 2008 Willer et al, 2012 Current study, 2020
Interval, y
Total esophagectomies
Patients in study, n
Follow-up months, median
Minimally invasive, %
THE, %
Crural fixation
Neoadjuvant therapy, %
Routine imaging
21
2182
2182
23
Unknown
Unknow n
Unknown
Unknown
No
11
851
851
Unknown
41
27
Some
62
No
7
Unknown
120
26
100
0
Unknown
71
Yes
13.5
199
199
26
Unknown
98
Unknown
54
Yes
2
Unknown
36*
Unknown
100
100
Unknown
44
No
14
657
488
18
66
17
No
66
Yes
13.4
390
390
Unknown
100
0
No
Unknown
No
7
554
440
52
7
23
Some
Unknown
Yes
16
273
273
Unknown
25
15
Some
62
No
8
Unknown
114
Unknown
100
94
Yes
Unknown
Yes
9
Unknown
192
8
100
100
Yes
67
Yes
12
1075
1075
Unknown
54
0
Yes
Unknown
No
6
133
39†
Unknown
49
0
Yes
69
Yes
6.5
310
258
24
60
73
No
68
Yes
3
* all esophagectomies performed robotically † all esophagectomies performed using Mckeown approach THE, transhiatal esophagectomy
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Table 5. Results from Prior Literature Describing Hiatal Hernia after Esophagectomy
Study
Price et al, 2011 Gooszen et al, 2018 Benjamin et al, 2015 Narayanan et al, 2015 Sutherland et al, 2011 Brenkman et al, 2017 Severino et al, 2016 Ganeshan et al, 2013 Messenger et al, 2015 Bronson et al, 2014 Crespin et al, 2016 Kent et al,
HH, postesophagectomy, n
Time to HH diagnosis, months, median
Symptomatic HH, n
HH repaired, n
HH mortality, n
HH requiring bowel resection, n
HH recurrence, n
Multivariable predictors of post esophagectomy HH
HH, n
15
21
15
13
15
0
2
2
NA
21
6
Unknown
21
21
1
Unknown
4
MIS; Ivor-Lewis
7
Unknown
7
5
6
0
0
1
NA
10
29
10
10
10
0
0
0
NA
7
Unknown
Unknown
7
7
1
3
Unknown
NA
45
20
Unknown
31
45
3
Unknown
4
BMI < 25
32
10
Unknown
22
32
0
1
6
NA
67
Unknown
33
8
9
1
Unknown
4
Male; BMI < 25; THE
11
Unknown
11
11
11
0
0
2
NA
9
14†
8
4
11*
0
1
3*
NA
22
Unknown
Unknown
7
7
0
0
1
NA
24
32†
24
20
22
1
Unknown
6
NA
3
2008 Willer et al, 2012 Current Study, 2020
5
14 †
4
0
3
Unknown
0
Unknown
NA
79
31
79
44
17
0
0
5
THE, NAT
* one patient had 2 recurrences † mean HH, hiatal hernia; NA, not analyzed; MIS, minimally invasive surgery; THE, transhiatal esophagectomy; NAT, neoadjuvant therapy
3
Figure Legend Figure 1. Comparing rates of hiatal herniation of small and/or large bowel post esophagectomy (HHBPE) in patients who satisfied both, only one, or none of the two significant predictors of HHBPE: neoadjuvant therapy and a transhiatal approach Figure 2. An example of hiatal herniation of colon into the left thorax post esophagectomy. Patient had primary repair of hiatal herniation of small and/or large bowel post esophagectomy and has not recurred.
3
Precis Hiatal hernia after esophagectomy is an increasingly recognized complication that can be seen weeks or years post-resection. Transhiatal approach and neoadjuvant therapy are significant risk factors for this complication. While most patients follow a benign course, some will develop severe symptoms that require surgical intervention.
3