Clinical Impact of Upper Extremity Deep Vein Thrombosis in the Retrosternal Reconstruction After Esophagectomy

Upper extremity deep vein thrombosis (UEDVT) is relatively rare but cannot be 27 negligible because it can cause fatal complications. Although it is reported that 28 the occurrence rate of UEDVT has increased due to central venous catheter 29 (CVC), cancer, and surgical invasion, there are still limited information for 30 esophagectomy. The aim of this study was to evaluate the clinical factors, 31 including CVC placement and thromboprophylaxis approach, as well as 32 retrosternal space’s width as a predictive factor for UEDVT in patients receiving 33 esophagectomy.


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Background 26 Upper extremity deep vein thrombosis (UEDVT) is relatively rare but cannot be 27 negligible because it can cause fatal complications. Although it is reported that 28 the occurrence rate of UEDVT has increased due to central venous catheter 29 (CVC), cancer, and surgical invasion, there are still limited information for 30 esophagectomy. The aim of this study was to evaluate the clinical factors, 31 including CVC placement and thromboprophylaxis approach, as well as 32 retrosternal space's width as a predictive factor for UEDVT in patients receiving 33 esophagectomy.

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This study included 66 patients who underwent esophagectomy with retrosternal 36 reconstruction using a gastric tube. All patients routinely underwent contrast- were measured by preoperative CT, and the ratio of (a) to (b) was defined as the 42 width of retrosternal space.

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Among all patients, 11(16.7%) suffered from UEDVT, and none was 45 preoperatively received CVC placement, while 7 were inserted in non-UEDVT 46 cases. Retrosternal space's width in patients with UEDVT was significantly 47 smaller than that in patients without UEDVT (0.17 vs. 0.26; P < 0.0001). A cutoff value of the width was 0.21, which has high sensitivity (87%) and specificity (82%) 49 for UEDVT prediction,respectively. 50 Conclusion 51 The existence of CVC may not affect the development of UEDVT, but 52 preoperative evaluation of retrosternal ratio may predict the occurrence of UEDVT.

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It is generally accepted that VTE is a concerning matter, which has been 83 reported to be 2.9 to 7.3% and could lead to pulmonary embolism (PE) and other 84 respiratory sequelae (5) (6). As well as lower extremity deep vein thrombosis 85 (LEDVT), upper extremity deep vein thrombosis (UEDVT), which occurs in the 86 subclavian, axillary, internal jugular, and/or brachial veins, cannot be negligible, 87 accounting for up to 10% of all documented DVTs (7). Its incidence has increased, 88 and the presence of central venous catheter (CVC) has been described as the 89 most significant risk factor of UEDVT, at least 50%, followed by cancer and major 90 surgery within 30days. Compared with patients with LEDVT, patients with UEDVT 91 tend to be younger and more common in cancer, and less likely to have acquired 92 or hereditary thrombophilia (7). The frequency of acute PE, a fatal complication 93 of UEDVT, is approximately 6-36% and 2-5% for recurrence at 12 months, which 94 should be identified in the early phase (7) (8) (9) (10). Therefore, early detection 95 by routine examination is crucial, and it is worth investigating the usefulness of 96 various diagnostic tools, including Computed Tomography (CT) (7).

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In esophageal cancer patients who underwent esophagectomy followed by factor for UEDVT (11). However, in the previous study, all the participants 105 received CVC before esophagectomy, and it has not been described whether 106 CVC placement increases the UEDVT occurrence. In addition, the efficacy of 107 postoperative thromboprophylaxis, low-molecular-weight heparin (LMWH), has 108 not been estimated.

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In the present study, we confirmed the effectiveness of retrosternal space    The data were analyzed using Prism version 9.0.0 (86) (GraphPad Software 164 LLC, San Diego, CA, USA). Continuous data were compared between the two 165 groups using the Mann-Whitney U test or Student's t test. Categorical data were compared using the Chi-square test. To identify risk factors related to UEDVT, 167 univariate analyses were performed using the Chi-square test. Those variables 168 remaining in the logistics equation at the last step were considered as 169 independent risk factors. P value <0.05 was considered statistically significant.

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The optimal cutoff point of the width of the retrosternal space for the prediction of 171 UEDVT was determined so that the Youden index (sensitivity + specificity -1) 172 would be maximized using receiver operating characteristic (ROC) curve analysis. 176 All the esophagectomies were conducted with retrosternal reconstruction.  (Table 1). Also, there was no significant difference 181 between 2-field and 3-field lymph node dissection(p=0.46). Among the 11 UEDVT 182 patients (Table 2) (Table 3). This result indicated the importance of 203 evaluating the retrosternal space as a predictive risk factor before 204 esophagectomy.

Correlation between UEDVT and CVC after esophagectomy with
206 retrosternal reconstruction. 207 Among UEDVT cases, none was preoperatively received CVC placement, 208 while 7 were inserted in non-UEDVT cases (n=55), and there was no correlation 209 between UEDVT and CVC placement (Table 4, (Table 4). predominant cause of secondary UEDVT is a CVC placement, which occupies at 229 least two-thirds, followed by cancer and major surgery within 30days (7).

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Malignancy has been reported to increase the risk of UEDVT in 18-fold (17), and 231 the presence of CVC scored with an odds ratio of 9.7(CI=7.8 to 12.2) (18). In our 232 present study, the incidence of UEDVT was 16.7% in 66 consecutive patients 233 who underwent esophagectomy with retrosternal gastric tube reconstruction, 234 which is less frequent than the previous report that the incidence of UEDVT was 235 25.5% in retrosternal gastric tube reconstruction (11). All the UEDVTs in our stockings, but there are few references with regard to UEDVT; thus, it is generally 283 recommended to take the same approach as for LEDVT (21) (22). In all our cases, 284 LMWH was administered subcutaneously as postoperative thromboprophylaxis, 285 but the frequency of UEDVT was almost the same as previously reported.

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Although the preventive effect for UEDVT has not been clarified, the effectiveness 287 of low-molecular-weight-heparin has been reported for lower extremity deep vein 288 thrombosis, and it seems to be worthwhile to keep administering it. The definition of UEDVT was confirmed by routine CT scan at postoperative 299 4 th day (POD) in our study. CT scan has high sensitivity and specificity with 91% 300 and 93%, respectively (26). Based on that, we conducted our present study, 301 whereas it is worthwhile to evaluate the effectiveness of compression ultrasound 302 is often preferred as a less expensive and readily available alternative, which has 304 high sensitivity (97%) and specificity (96%) (26). However, the usefulness of 305 Ultrasonography is still controversial regarding clinical probability and objectivity, 306 and although there is a clinical decision score such as the Constans score for 307 UEDVT, the diagnostic accuracy is not high enough to justify using this score as 308 a standalone tool (27). D-dimer's sensitivity and specificity at the cutoff value of 309 500 μg/L were 92-100% and 14-60%, respectively. It indicates that the sensitivity 310 of D-dimer testing as high as in patients with suspected LEDVT, whereas the 311 accuracy of specificity remains to be discussed (10) (28). In the present study, 312 D-dimer's elevation was confirmed with almost all the cases receiving 313 esophagectomy, and it was not useful as a specificity marker by itself. Taken 314 together, we believed that CT scan in the early period after esophagectomy might 315 be superior to the other diagnostic tools.

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Limitations of this study are the retrospective data nature, the small number of 318 patients at a single institute. Comparison of usefulness for prevention with or 319 without anticoagulation was not validated. However, since this is the first study to 320 describe the evaluation of UEDVT with or without CVC placement and 321 postoperative thromboprophylaxis after esophagectomy, we believe that the 322 present study will provide useful information to clinicians, and further 323 accumulation of retrospective and prospective studies is required.

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In conclusion, the incidence of UEDVT detected by routine POD4 CT was 326 16.7% in patients who underwent esophagectomy with retrosternal gastric tube reconstruction. All UEDVT occurred in the proximal left-side veins. The existence 328 of CVC may not affect the generation of UEDVT, but preoperative evaluation of 329 retrosternal ratio may predict the occurrence of UEDVT.  The width of retrosternal space was defined by the ratio of (a) to (b).

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(a); the back of the sternum to the ventral part of the brachiocephalic artery.

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(b); the back of the sternum to the ventral part of the vertebra.

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To evaluate the retrosternal space, Contrast-enhanced CT was conducted 457 preoperatively within three months.   The width of retrosternal space was de ned by the ratio of (a) to (b). (a); the back of the sternum to the ventral part of the brachiocephalic artery. (b); the back of the sternum to the ventral part of the vertebra.
To evaluate the retrosternal space, Contrast-enhanced CT was conducted preoperatively within three months.

Figure 3
Non-UEDVT case after esophagectomy with gastric tube through the retrosternal reconstruction route.
Open arrows indicate the compression of the left brachiocephalic vein by gastric tube and brachiocephalic artery.

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