Jie Yue

Lymph node dissection for Siewert II esophagogastric junction adenocarcinoma: A retrospective study of 3 surgical procedures

Abstract The present study was aimed to investigate the application of right thansthoracic Ivor–Lewis (IL), left transthoracic (LTT), and left thoracoabdominal (LTA) approach in Siewert type II adenocarcinoma of esophagogastric junction (AEG). The data of 196 patients with Siewert type II AEG received surgical resection in our cancer center between January 2014 and April 2016 was retrospectively analyzed. Finally, 136 patients met the inclusion criteria were enrolled in the study and divided into the IL (47 cases), LTT (51 cases), and LTA group (38 cases). Clinical and short-term treatment effects were compared among the 3 groups. The patients with weight loss, diabetes, and heart disease increased in the LTT group (P = 0.054, P = 0.075, and P = 0.063, respectively). Operation time was significantly longest in the IL group (P < 0.001), but the amount of bleeding and tumor size did not significantly differ among the 3 groups (P = 0.176 and P = 0.228, respectively). The IL group had the significantly longest proximal surgical margin (P < 0.001) and most number of total (P < 0.001) and thoracic lymph nodes (P < 0.001) dissected. Both the IL and LTA groups had more abdominal lymph nodes dissected than the LTT group (P < 0.001). In general, the IL and LTT groups had the highest dissection rates of every station of thoracic (P < 0.05) and lower mediastinal lymph nodes (P < 0.05), respectively. The dissection rate of the paracardial, left gastric artery, and gastric lesser curvature lymph nodes did not differ significantly among the 3 groups (P > 0.05), but the dissection rate of the hepatic artery, splenic artery, and celiac trunk lymph nodes was significantly highest in the IL group (P < 0.05). Postoperative hospital stay, perioperative complications, and mortality did not differ significantly among the 3 groups (P > 0.05). Compared with the traditional left transthoracic approach, the Ivor–Lewis approach did not increase the perioperative mortality and complication rates in Siewert type II AEG, but obtained satisfactory length of the proximal surgical margin, and was better than the left transthoracic approach in thoracic and abdominal lymph node dissection. However, the advantages of Ivor–Lewis procedure requires further follow-up and validation through prospective randomized controlled trials.

Lymph node metastasis in thymic malignancies: A Chinese multicenter prospective observational study

Objectives To study the incidence and pattern of lymph node metastases in thymic malignancies. Methods This multicenter prospective observational trial with intentional lymph node dissection was carried out by the Chinese Alliance for Research in Thymomas (ChART). Data on patients with thymic tumors without pretreatment were collected prospectively. Results from this prospective study were then compared with those from a previously reported ChART retrospective study. Results Among 275 patients, metastasis was detected in 41 nodes (3.04%) in 15 patients (5.5%). The rate of lymph node metastasis was 2.1% (5/238) in patients with thymomas, 25% (6/24) in those with thymic carcinomas, and 50% (4/8) in those with neuroendocrine tumors (P < .001). The rate of lymph node metastasis in category T1 to T4 tumors was 2.7% (6/222) in T1, 7.7% (1/13) in T2, 18.4% (7/38) in T3, and 50% (1/2) in T4 (P < .001). Nodal involvement was significantly higher compared with the ChART retrospective study (5.5% vs 2.2%; P = .002), although the 2 groups were comparable in terms of tumor stage and histology. Metastasis was found in N1 nodes in 13 patients (86.7%) and in N2 nodes in 8 patients (53.3%); 6 patients (40%) had simultaneous N1/N2 diseases and 6 (40%) had multistation involvement. Based on World Health Organization histological classification and Union for International Cancer Control T category, patients were divided into a low‐risk group (1/192; 0.5%) with T1‐2 and type A‐B2 diseases and a high‐risk group (14/83; 16.9%) of category T3 and above or histology B3 and above tumors for nodal metastasis (P < .001). On multivariate analysis, type B3/thymic carcinoma/neuroendocrine tumors, category T3 or above, and N2 dissection predicted a greater likelihood of finding nodal metastasis. Conclusions Lymph node involvement in thymic malignancies is more common than previously recognized, especially in tumors with aggressive histology and advanced T category. Intentional lymph node dissection increases the detection of nodal involvement and improves accuracy of staging. In selected high‐risk patients, systemic dissection of both N1and N2 nodes should be considered for accurate tumor staging.

High expression of glucose-regulated protein 78 (GRP78) is associated with metastasis and poor prognosis in patients with esophageal squamous cell carcinoma

Background Glucose-regulated protein 78 (GRP78) plays an important role in the invasion and metastasis of many human cancers. However, the role of this protein in the progression of invasion and metastasis in esophageal squamous cell carcinoma (ESCC) remains elusive. Patients and methods Immunohistochemistry and Western blot were performed to analyze GRP78 expression in 92 patients with primary ESCC. The correlation of GRP78 expression with clinicopathological factors was analyzed. In vitro, the expression levels of GRP78 were downregulated by small interfering RNA transfection in TE-1 and CaEs-17 ESCC lines. Cell invasion and migration assays were applied to determine the invasion and migratory abilities of ESCC cells. Results Compared with GRP78 in adjacent normal esophageal tissues, GRP78 was overexpressed in ESCC tissues. High GRP78 expression was significantly correlated with positive lymph node metastasis (P=0.035) and advanced tumor stage (P=0.017). Survival analysis revealed that high GRP78 expression was significantly associated with shorter overall survival (P=0.037). In multivariate analysis, GRP78 overexpression was identified as an independent prognostic factor for overall survival (P=0.011). si-GRP78 can significantly decrease the GRP78 expression level and reverse the invasion and migratory abilities of ESCC cells in TE-1 and CaEs-17 cell lines. Conclusion These findings demonstrated that high expression of GRP78 was associated with disease progression and metastasis in ESCC and might serve as a novel prognostic marker for patients with ESCC.

Development of a novel biomarker model for predicting preoperative lymph node metastatic extent in esophageal squamous cell carcinoma 1

The number and range of lymph node metastasis (LNM) are critical prognostic factors in esophageal squamous cell carcinoma (ESCC). Preoperative serum biomarkers are reported to be associated with LNM. However, whether these markers can precisely predict the extent of LNM is not known. The aim of this study was to evaluate the predictive value of preoperative serum SCC-Ag, Cyfra21-1, CEA, CA19-9 and CA72-4 for LNM number and range by retrospectively investigating 577 ESCC patients undergone esophagectomy from 2007-2010. In this study, the positive rate of SCC-Ag and CA19-9 were associated with pN stage. Significant differences were found in CEA and CA19-9 between pN0-1 stage patients and pN2-3 stage patients. However, in subgroup analysis (patients with pN0-1), significant difference was found only in SCC-Ag between pN0 and pN1 stage patients (P=0.003). Middle thoracic ESCC patients were Chosen to analyze the correlation between the range of LNM and biomarkers. SCC-Ag was correlated with paraesophageal and paracardial lymph nodes, but not correlated with subcarinal and left gastric artery lymph nodes. Interestingly, the results of CEA were opposite to that of SCC-Ag. CA19-9 was associated with subcarinal and paracardial LNM (P=0.000, P=0.038). Based on the results, a model incorporated SCC-Ag, CEA and CA19-9 was constructed. The rate of patients with pN2-3 stage was 15.4% and 54.4% in group 1 and 4 of our model. In summary, SCC-Ag was associated with early lymph node metastatic stage, and CEA and CA19-9 have a close relationship with advanced lymph node metastatic stage. The model combining SCC-Ag, CEA and CA19-9 might help identify the preoperative extent of LNM for a subgroup of ESCC patients that can be benefited from neoadjuvant therapy.

Pretreatment biopsy for histological diagnosis and induction therapy in thymic tumors

BACKGROUND This study was to investigate the value of pretreatment biopsy for histological diagnosis and induction therapies in the management of locally advanced thymic malignancies. METHODS The clinical pathological data of patients with thymic tumors in the Chinese Alliance for Research in Thymomas (ChART) who underwent biopsy before treatment from 1994 to December 2012 were retrospectively reviewed. The application trend of preoperative histological diagnosis and its influence on treatment outcome were analyzed. RESULTS Of 1,902 cases of thymic tumors, 336 (17.1%) had undergone biopsy for histological diagnosis before therapeutic decision was decided. In recent years, percentage of pretreatment histological diagnosis significantly increased in the later ten years than the former during the study period (P=0.008). There was also a significant increase in thoracoscopy/mediastinoscopy/E-BUS biopsy as compared to open biopsy (P=0.029). Survival in Patients with preoperative biopsy for histology had significantly higher stage lesions (P=0.000) and higher grade malignancy (P=0.000), thus a significantly lower complete resection rate (P=0.000) and therefore a significantly worse survival than those without preoperative biopsy (P=0.000). In the biopsied 336 patients, those who received upfront surgery had significantly better survival than those received surgery after induction therapy (P=0.000). In stage III and IVa diseases, the R0 resection rate after induction therapies increased significantly as compared to the surgery upfront cases (65.5% vs. 46.2%, P=0.025). Tumors downstaged after induction had similar outcomes as those having upfront surgery (92.3% vs. 84.2%, P=0.51). However, tumors not downstaged by induction had significantly worse prognosis than those downstaged (P=0.004), and fared even worse than those having definitive chemoradiation without surgery (37.2% vs. 62.4%, P=0.216). CONCLUSIONS It is crucial to get histological diagnosis for thymoma before surgery or adjuvant treatment and minimally invasive biopsy should be undertaken. Although in our study we could not find the benefit of induction chemotherapy before surgery in survival and recurrence rate, it could increase the R0 resection rate compared with direct surgery in late stage (III and IVa).

Prognostic significance of preoperative and postoperative CK19 and CEA mRNA levels in peripheral blood of patients with gastric cardia cancer

AIM To evaluate the clinical and prognostic significance of preoperative and postoperative cytokeratin 19 (CK19) and carcinoembryonic antigen (CEA) mRNA levels in peripheral blood of patients with gastric cardia cancer (GCC). METHODS We detected the preoperative and postoperative mRNA levels of CK19 and CEA in peripheral blood of 129 GCC patients by using reverse transcription-polymerase chain reaction and evaluated their clinical and prognostic significance by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard analysis. A new prognostic model which stratified patients into three different risk groups was established based on the independent prognostic factors. RESULTS Elevated preoperative and postoperative CK19 and CEA mRNA levels in peripheral blood of GCC patients were associated with lymph node metastasis. Univariate analysis showed that tumor size, histological grade, depth of tumor invasion, lymph node metastasis, preoperative CK19 mRNA, and preoperative and postoperative CEA mRNA levels were correlated with the prognosis of GCC patients. The multivariate analysis showed that lymph node status (P = 0.018), preoperative CK19 (P = 0.035) and CEA (P = 0.011) mRNA levels were independent prognostic factors for overall survival (OS). The 5-year OS rates for the low-, intermediate-, and high-risk groups were 48.3%, 22.6%, and 4.6%, respectively (P < 0.001). CONCLUSION Elevated preoperative CK19 and CEA mRNA levels may be regarded as promising biomarkers for predicting lymph node metastasis and poor prognosis in patients with GCC. This new prognostic model may help us identify the subpopulations of GCC patients with the highest risk.