Clinical value of routine contrast esophagram in the diagnosis of anastomotic leakage for three-incision esophagectomy with cervical anastomosis / 中华外科杂志

Objective: To examine the clinical value of routine contrast esophagram (RCE) for the diagnosis of anastomotic leakage (AL) after three-incision esophagectomy with cervical anastomosis. Methods: Clinical data of 1 022 patients with esophageal cancer who underwent McKeown three-incision esophagectomy with cervical anastomosis from January 2015 to December 2019 at Department of Minimally Invasive Esophageal Surgery, Tianjin Medical University Cancer Hospital and Institute were analyzed retrospectively. There were 876 males and 146 females, aging(M(IQR)) 48(16) years (range: 36 to 84 years). There were 253 patients (24.8%) with neoadjuvant therapy, and 817 patients (79.9%) with minimally invasive esophagectomy. According to the diagnosis and treatment habits of the attending surgeons, 333 patients were included in the RCE group, and RCE was performed on the 7th day postoperative, while 689 patients were included in the non-RCE group, and RCE was performed when the patients had suspicious symptoms. Taking clinical symptoms, RCE, CT, endoscopy and other methods as reference to the diagnosis of AL, the sensitivity and specificity were used to analyze and evaluate the efficacy of RCE for the diagnosis of AL. The data were compared by U test or χ² test between groups. Results: The incidence rate of AL after three-incision esophagectomy was 7.34% (75/1 022), including 30 cases in the RCE group and 45 cases in the non-RCE group (9.0%(30/333) vs. 6.5%(45/689), χ²=2.027, P=0.155). The diagnostic time of AL was 9(5) days postoperative (range: 4 to 30 days). Among them, 23 cases showed cervical leakages, 50 cases showed intro-thoracic leakages, and 2 cases both cervical and intro-thoracic leakages. The diagnostic time of patients with intro-thoracic leakages was longer than that of cervical leakages (10(4) days vs. 6(3) days, Z=-2.517, P=0.012). Among the 333 patients in the RCE group, 16 cases of RCE indicated leakages including 11 cases of true positive and 5 cases determined to be false positive, while 317 cases indicated no abnormalities including 19 cases developed leakages. The sensitivity and specificity of RCE to detect AL were 36.7%(11/30) and 98.3%(298/333), respectively. The Youden-index was 0.35, and the diagnostic accuracy was 92.8%(309/333). The positive and negative predictive value were 11/16 and 94.0%(298/317), respectively. Conclusions: Routine contrast esophagram after three-incision esophagectomy with cervical anastomosis has low sensitivity and high specificity in the diagnosis of AL. The diagnostic time of AL is the 9th day after surgery. It is necessary to prolong the observation time clinically, and combine RCE with CT, endoscopy and other inspection methods for diagnosis.

Clinical significance of serum high-mobility group box 1 detection in esophageal squamous cell carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the level of serum high-mobility group box 1 (HMGB1) in patients with esophageal squamous cell carcinoma (ESCC) and the feasibility of HMGB1 as a tumor marker.</p><p><b>METHODS</b>Serum HMGB1, carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen (Cyfra21-1) and squamous cell carcinoma antigen (SCC) were measured by enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence immunoassay (ECLIA) and microparticle enzyme immunoassay (MEIA) respectively in 78 patients with ESCC preoperatively as well as a month after esophagectomy. At the same time, serum HMGB1, CEA, Cyfra21-1 and SCC of 60 healthy adult volunteers were detected with the same method. The unilateral P95 value of serum HMGB1 (>96 μg/L) was defined as positive. According to the Roche kit diagnostic criteria, CEA>5.0 μg/L, Cyfra21-1>3.3 μg/L and SCC>1.5 μg/L were defined as positive.</p><p><b>RESULTS</b>The preoperative positive ratio of serum HMGB1 in 78 patients with ESCC was 84.6%, and the level of serum HMGB1 was associated with the tumor size, infiltration depth, lymph node metastasis and tumor stage (P<0.01 or P<0.05). One month after esophagectomy, the level of serum HMGB1 in ESCC declined significantly compared with the preoperative level (P<0.01), and the level of serum HMGB1 in T4, N1, stage III was higher compared to corresponding T, N and tumor stage (P<0.01 or P<0.05). The positive ratio of CEA, Cyfra21-1 and SCC was 10.3%, 25.6% and 42.3% respectively in 78 ESCC patients preoperatively, so the sensitivity of these tumor markers was lower. One month after esophagectomy, serum Cyfra21-1 and serum SCC were significantly decreased compared to the preoperative level (P<0.01). However, there was no significant difference of preoperative serum CEA compared to a month after esophagectomy in ESCC (P>0.05). The specificity of HMGB1, CEA, Cyfra21-1 and SCC were 93.3%, 88.3%, 90.0% and 93.3% respectively.</p><p><b>CONCLUSION</b>Compared to CEA, Cyfra21-1 and SCC, serum HMGB1 in ESCC patients is easier for detection and its sensitivity and specificity are higher, which may be used as a marker in diagnosis, prediction of prognosis and monitor of postoperative recurrence of ESCC.</p>

Effect of HMGB1 on the VEGF-C expression and proliferation of esophageal squamous cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the effect of HMGB1 on the VEGF-C expression and proliferation of esophageal squamous cancer cells as well as its possible mechanism.</p><p><b>METHODS</b>A cassette encoding siRNA targeting HMGB1 mediated by rAAV was constructed, the rAAV-siHMGB1-hrGFP, and a vector encoding siRNA mismatching HMGB1 was constructed, the rAAV-miHMGB1-hrGFP. This experiment in vitro included three groups, namely, the blank control group (group A) of KYSE150 cells transfected by rAAV-hrGFP, negative mismatch control group (group B) of KYSE150 cells transfected with rAAV-miHMGB1-hrGFP, and RNA interference group (group C) of KYSE150 cells transfected with rAAV-siHMGB1-hrGFP. We examined the expression of HMGB1 mRNA and protein in the three group cells by real-time PCR and Western blot after 24 h and 48 h, respectively. Then, VEGF-C expression and cell proliferation in the three group cells with or without sRAGE, as an inhibitor of RAGE signal pathway, were assayed by ELISA and MTT after 24 h.</p><p><b>RESULTS</b>The expression of HMGB1 mRNA and protein in KYSE150 cells in vitro in the group C transfected with rAAV-siHMGB1-hrGFP at the final concentration of 2×10(6) v.g/cell was significantly lower than that of the group A or B after 24 h and 48 h (P < 0.01). The VEGF-C expression of KYSE150 cells was (502.43 ± 13.10) pg/ml in the group C, significantly reduced in comparison with that of the group A (686.40 ± 10.94) pg/ml or group B (682.31 ± 9.61) pg/ml after 24 h (P < 0.05). At the same time, the proliferation of KYSE150 cells in the group C was significantly inhibited compared with that of groups A and B after 24 h (P < 0.01). Moreover, sRAGE at the final concentration of 0.2 µg/ml inhibited the VEGF-C expression and proliferation of KYSE150 cells compared with the corresponding group without sRAGE after 24 h (P < 0.01 or P < 0.05). However, there was no significant difference of the VEGF-C expression and proliferation of KYSE150 cells with sRAGE in the group C compared with that of cells with sRAGE of the group A or group B after 24 h (P > 0.05).</p><p><b>CONCLUSIONS</b>In esophageal squamous cell carcinoma, HMGB1 can promote the VEGF-C expression and proliferation of the cancer cells through RAGE signal pathway, and HMGB1-RAGE may become a potential target for cell proliferation and lymph node metastasis of this cancer.</p>