[Clinical value of routine contrast esophagram in the diagnosis of anastomotic leakage for three-incision esophagectomy with cervical anastomosis].

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.

[Current status and prognosis of immune checkpoint inhibitors for esophageal cancer].

Programmed cell death protein 1 (PD-1/CD279) and cytotoxic T Lymphocyte Antigen-4 (CTLA-4) are important immune checkpoints, through the role of the corresponding ligands and inhibit T cell activation and production of cytokines, in maintaining the body's vital role in peripheral tolerance. The use of anti-CTLA-4/PD-1 /PD-L1 monoclonal antibodies to block the tumor signaling pathway has shown excellent anti-tumor efficacy in a variety of solid tumors, and it is expected that immunotherapy will be available for the treatment of 60% advanced tumors in the next decade. Esophageal cancer is one of the major causes of cancer-related deaths worldwide, and its 5-year survival rate is generally low. Currently, radiotherapy, chemotherapy, and surgery are the standard treatments for esophageal cancer, and there is no effective treatment scheme for patients with esophageal cancer who fail to respond to standard treatment. Due to the diversity of somatic cell gene mutations and the generation of neo-antigens in esophageal cancer, immunotherapy has become a feasible treatment scheme to improve the prognosis of esophageal cancer. In this situation, the application of immunotherapy for esophageal cancer or more specific immune checkpoint inhibitors has gradually become the focus of the treatment of esophageal cancer. Nowadays, the research of immune checkpoint inhibitors, such as ipilimumab, tremelimumab, pembrolizumab, nivolumab and avelumab on esophageal cancer is proceeding at an amazing speed. The phase Ⅰ b clinical study of immunotherapy for esophageal cancer, which previously attracted great interest, has been replaced by the phase Ⅲ clinical study, and the results of the relevant studies also show a good prospect for the application of immune checkpoint inhibitors for esophageal cancer. However, the prediction of therapeutic effect and the selection of the best candidates still need to be further studied.

[Comparison of the effect of lymph node dissection performed by Ivor-Lewis or left-sided thoracic esophagogastrectomy for Siewert type â ¡ adenocarcinoma of the esophagogastric junction].

Objective: To compare the extent of lymphadenectomy and postoperative complications between Ivor-Lewis procedure and left sided thoracotomy in patients with Siewert type Ⅱ adenocarcinoma of the esophagogastric junction (AEG). Methods: The clinical data of 101 patients with Siewert type Ⅱ EG who received surgical treatment between January 2014 and September 2015 in the Department of Esophageal Cancer, Tianjin Medical University Cancer Hospital were analyzed retrospectively. These patients were divided into Ivor-Lewis group (IL, n=38) and left- sided thoracotomy group (LT, n=63) according to the operation mode. The number and extent of dissected lymph nodes and postoperative complications were compared between the two groups. Results: The surgical blood loss, length of postoperative stay, anastomotic leakage, pulmonary infection, respiratory failure and complications of incision of the two groups showed no significant differences (P>0.05 of all). The operation time of IL group was 200 min, significantly longer than the LT group (120 min, P<0.05). The number of resected lymph nodes in the IL and LT groups were (20±9) and (13±7), respectively, with a statistically significant difference (P<0.001). Significantly more thoracic lymph nodes (7±5) were harvested in the IL group than in the LT group (2±2, P<0.001), and the number of resected abdominal lymph nodes in the IL and LT groups were (13±8) and (11±7), with a non-significant difference (P=0.157). As regarding the lymph node dissection rate, the IL approach was obviously better than the LT approach in the following lymph node stations: superior mediastinal nodes, subcarinal nodes, left hilar nodes, right hilar nodes, middle thoracic paraesophageal nodes, lower thoracic paraesophageal nodes, lymph nodes along the common hepatic artery, and lymph nodes along the splenic artery(P<0.05 for all). Conclusions: The Ivor-Lewis procedure achieves better thoracic and abdominal lymph node dissection, and does not cause more postoperative complications than the left-sided thoracotomy in patients with Siewert type Ⅱ AEG. However, these findings need to be confirmed by large-scale randomized clinical trial in the future.

[Lymph node metastasis and prognostic factors for T1 esophageal cancer].

Objective: To evaluate the lymph node metastasis (LNM) pattern and related prognostic factors for T1 esophageal cancer. Methods: Clinical data of 143 cases of pT1 esophageal cancer patients (120 male and 23 female patients with median age of 60 years) who underwent esophagectomy and lymph node resection during January 2011 and July 2016 at the Department of Esophageal Cancer of Tianjin Medical University Cancer Institute and Hospital were reviewed, including 50 cases of T1a patients and 93 cases of T1b patients. The LNM pattern was analyzed and the prognostic factors related to LNM were assessed by χ2 test and Logistic regression analysis. Results: Of 143 patients, 25 patients had LNM. The LNM rates were 17.5% for pT1 tumors, 16.0%(8/50) for pT1a tumors, and 22.6%(21/93) for T1b tumors. Of 25 patients with LNM, one patient had cervical metastasis, 15 patients with thoracic metastasis, and 17 patients with abdominal metastasis. The relatively highest LNM sites were laryngeal recurrent nerve (8 cases), left gastric artery (8 cases), right and left cardiac (6 cases) and thoracic paraesophageal (5 cases). Logistic regression analysis showed that the depth of tumor infiltration (OR=4.641, 95%CI: 1.279 to 16.836, P=0.020), tumor size (OR=5.301, 95%CI: 1.779 to 15.792, P=0.003), tumor location (OR=3.238, 95% CI: 1.248 to 8.401, P=0.016), and tumor differentiation (OR=5.301, 95%CI: 1.719 to 16.347, P=0.004) were independent prognostic factors related to LNM for T1 esophageal cancer. Tumor size (OR=4.117, 95% CI: 1.228 to 13.806, P=0.022) was an independent risk factor related to thoracic LNM, and the vessel invasion (OR=6.058, 95% CI: 1.228 to 29.876, P=0.027) and tumor location (OR=8.113, 95% CI: 1.785-36.872, P=0.007) were independent prognostic factors related to abdominal LNM. Conclusions: T1 esophageal cancer has a relatively high LNM rate, and the depth of tumor infiltration, tumor size, tumor location and tumor differentiation are correlated with LNM. The LNM risk and extent must be considered comprehensively in decision-making of a better surgical treatment and lymph node resection strategy.

[Association between chronicity of HBV infection and host immunity].

The prognosis of hepatitis B virus (HBV) infection is determined by innate immunity, adaptive immunity, and a variety of regulatory factors in the host. Controversy still exists over the role of innate immunity in the progression of HBV infection. Adaptive immunity, especially the immune response mediated by CD8+ T cells, plays an important role in HBV clearance. However, in patients with chronic infection, such CD8+ T cells are often exhausted and associated with various regulatory factors including programmed cell death 1 and T-cell immunoglobulin mucin-3. This article elaborates on the association of chronicity of HBV infection with host immune system and various regulating factors.

Effect of miR-223 on thrombophlebitis rats through regulating Toll-like receptor signaling pathway.

OBJECTIVE: To explore the effect of the micro ribonucleic acid (miR)-223 on the thrombophlebitis rats by regulating the Toll-like receptor (TLR) signaling pathway. MATERIALS AND METHODS: The rat model of thrombophlebitis was established, and miR-223 was silenced or overexpressed through lentiviral transfection. The rats were divided into miR-223 inhibitors group (Inhibitors group), miR-223 mimics group (Mimics group), and normal group (Control group). The transfection efficiency of miR-223 in venous tissues was detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR), the hemorheological indexes plasma viscosity (PV) and hematocrit (HCT) were observed, and the content of the serum inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-ß (TNF-ß) were detected via enzyme-linked immunosorbent assay (ELISA). Moreover, the fibrinolytic indexes plasminogen activator inhibitor (PAI) and the tissue-type plasminogen activator (t-PA) were detected, the morphological changes in the venous tissues were observed via hematoxylin-eosin (HE) staining, and the gene and protein expressions of the TLR signaling pathway were detected via RT-PCR and Western blotting. RESULTS: The expression of miR-223 was significantly increased in the Mimics group (p<0.05) and significantly decreased in the Inhibitors group (p<0.05). The high-shear and low-shear whole blood viscosity and HCT in the Inhibitors group were significantly higher than those in the Mimics group (p<0.05). The levels of serum IL-6, IL-1ß, and TNF-ß in the Inhibitors group were remarkably higher than those in the Mimics group (p<0.05). The Inhibitors group had a remarkably lower level of t-PA (p<0.05) and a remarkably higher level of PAI than the Mimics group (p<0.05). Besides, the inferior vena cava wall shed and disappeared due to complete necrosis in the Inhibitors group. In the Mimics group, the vascular lumen was slightly expanded, and the vascular wall had intact contour. It was found in the gene detection that the mRNA levels of TLR2, myeloid differential protein-88 (MyD88) and c-Jun N-terminal kinase (JNK) were evidently increased in the Inhibitors group, and the significant increases in the protein levels of TLR2 and MyD88 were also observed in the protein detection. CONCLUSIONS: The overexpression of miR-223 can inhibit the TLR signaling pathway, thereby promoting the recovery of thrombophlebitis rats.