Jianhua Fu

Outcome of elderly patients with oesophageal squamous cell carcinoma after surgery

Oesophagectomy may have morbidity and mortality rates that severely compromise long‐term survival in elderly patients. The aim of this study was to compare clinical outcomes in elderly patients with oesophageal squamous cell carcinoma (SCC) with those of younger controls.

Identification and Validation of Lymphovascular Invasion as a Prognostic and Staging Factor in Node-Negative Esophageal Squamous Cell Carcinoma

Introduction: Lymphovascular invasion (LVI) is a histopathological feature that is associated with an increased risk for micrometastasis. The aim of this study was to determine the prognostic and staging value of LVI among patients with esophageal squamous cell carcinoma (ESCC) undergoing esophagectomy. Methods: A prospective database of patients with ESCC was used to retrospectively analyze 666 cases to identify the relationship between LVI and survival, and to evaluate predictive accuracy of prognosis after combining LVI and the tumor, node, and metastasis (TNM) system. Pathological slides were reassessed by gastrointestinal pathologists according to the strict criteria; 1000‐bootstrap resampling was used for internal validation, and 222 cases from an independent multicenter database were used for external validation. Results: LVI was present in 33.8% of patients, and the proportion increased with advancing T and N classification. LVI was an independent predictor of unfavorable disease‐specific survival (DSS) (hazard ratio = 1.59, 95% confidence interval: 1.30–1.94) and disease‐free survival (DFS) (hazard ratio = 1.62, 95% confidence interval: 1.32–1.98) after T classification. Among node‐negative patients, LVI and T classification were two independent predictors of DSS and DFS (p < 0.001). The risk score model combing LVI and T classification improved the predictive accuracy of the TNM system for DSS and DFS by 3.5% and 4.8%, respectively (p < 0.001). The external validation showed congruent results. The DSS of TxN0MO disease with LVI was similar to the DSS of TxN1M0 (both p > 0.05). In contrast, LVI was not associated with DSS or DFS among node‐positive patients. Conclusions: The independent prognostic significance of LVI existed only in node‐negative patients with ESCC, and the combination of LVI and the TNM system enhanced the predictive accuracy of prognosis. After confirmation, node‐negative patients with LVI might be considered for upstaging in pathological staging.

Prognostic significance of the pN classification supplemented by body mass index for esophageal squamous cell carcinoma.

Body mass index (BMI) has been associated with the risk of esophageal cancer. But the influence of BMI on postoperative complications and prognosis has always been controversial.

Management of Thymic Tumors - Consensus Based on the Chinese Alliance for Research in Thymomas Multi-institutional Retrospective Studies

Thymic tumors are relatively rare malignancies comparing to other solid tumors in the chest (1). Its incidence is estimated to be at 3.93 per 1,000,000, which is about 1/00 of lung cancer and 1/25 of esophageal cancer in China. And it appears to be higher than that reported from North America, which is only 2.14 per 1,000,000 according to the SEER database. However, in the SEER database, the incidence rate was much higher in Asians (3.74 per 1,000,000) than in Caucasians (1.89 per 1,000,000) and close to the data from China. This implicates that there might be some ethnical and generic difference in thymic tumors. In the meantime, both these two registrations record only ‘malignant tumors’ that are clinically advanced diseases. A large part of early stage, low grade lesions are considered ‘benign tumors’ and thus, not registered. Therefore, the actual incidence of thymic tumors is much under-estimated. With the increasing use of screening for other malignancies such as lung cancer, it can be expected that more early stage thymic tumors would be discovered.

Comparison of the Masaoka-Koga staging and the International Association for the Study of Lung Cancer/the International Thymic Malignancies Interest Group proposal for the TNM staging systems based on the Chinese Alliance for Research in Thymomas retrospective database.

BACKGROUNDnTo compare the predictive effect of the Masaoka-Koga staging system and the International Association for the Study of Lung Cancer (IASLC)/the International Thymic Malignancies Interest Group (ITMIG) proposal for the new TNM staging on prognosis of thymic malignancies using the Chinese Alliance for Research in Thymomas (ChART) retrospective database.nnnMETHODSnFrom 1992 to 2012, 2,370 patients in ChART database were retrospectively reviewed. Of these, 1,198 patients with complete information on TNM stage, Masaoka-Koga stage, and survival were used for analysis. Cumulative incidence of recurrence (CIR) was assessed in R0 patients. Overall survival (OS) was evaluated both in an R0 resected cohort, as well as in all patients (any R status). CIR and OS were first analyzed according to the Masaoka-Koga staging system. Then, they were compared using the new TNM staging proposal.nnnRESULTSnBased on Masaoka-Koga staging system, significant difference was detected in CIR among all stages. However, no survival difference was revealed between stage I and II, or between stage II and III. Stage IV carried the highest risk of recurrence and worst survival. According to the new TNM staging proposal, CIR in T1a was significantly lower comparing to all other T categories (P<0.05) and there is a significant difference in OS between T1a and T1b (P=0.004). T4 had the worst OS comparing to all other T categories. CIR and OS were significantly worse in N (+) than in N0 patients. Significant difference in CIR and OS was detected between M0 and M1b, but not between M0 and M1a. OS was almost always statistically different when comparison was made between stages I-IIIa and stages IIIb-IVb. However, no statistical difference could be detected among stages IIIb to IVb.nnnCONCLUSIONSnCompared with Masaoka-Koga staging, the IASLC/ITMIG TNM staging proposal not only describes the extent of tumor invasion but also provides information on lymphatic involvement and tumor dissemination. Further study using prospectively recorded information on the proposed TNM categories would be helpful to better grouping thymic tumors for predicting prognosis and guiding clinical management.

Lymph node metastases in thymic malignancies: a Chinese Alliance for Research in Thymomas retrospective database analysis

OBJECTIVESnLymphatic involvement is believed to be relatively rare in thymic epithelial tumours. The incidence and prognostic significance of nodal metastases are still unclear. The goal of this study was to define the incidence and prognostic relevance of nodal metastasis in patients with thymic epithelial tumours, using a nationwide retrospective database of the Chinese Alliance for Research in Thymomas.nnnMETHODSnPatients who underwent upfront surgical resection without preoperative therapy were enrolled for the study. The International Thymic Malignancies Interest Group proposal of a new staging system for thymic epithelial tumours was used to redefine the pathological stage. The incidence of nodal metastasis and its relationship with clinicopathological characteristics and its impact on survival were examined accordingly.nnnRESULTSnA total of 1617 patients were enrolled in this study. Lymph node metastasis was identified in 35 patients (2.2%). No nodal involvement was found in type A, AB or B1 thymomas. The incidence of nodal metastasis in thymoma (B2/B3) and thymic carcinoma was 1.3% and 7.9%, respectively, and it was most commonly seen in patients with neuroendocrine thymic tumours (16.7%, Pu2009<u20090.001). According to the primary tumour invasion stage, incidences of nodal metastasis were 0.2% in T1, 6.9% in T2, 8.5% in T3 and 7.4% in T4 tumours (Pu2009<u20090.001). Gender, pleural or distant metastasis and resection status were also correlated with nodal metastasis (Pu2009<u20090.05) in univariable analysis. Multivariable analysis revealed that patients with non-thymoma histological characteristics (Pu2009<u20090.001) and tumours in non-T1 stage (Pu2009<u20090.001) had significantly greater risk of developing nodal metastasis. The overall survival of patients without nodal metastasis was significantly higher than that of patients with nodal involvement (Pu2009<u20090.001). Disease-free survival of patients after R0 resection without nodal metastasis was also significantly higher than those with nodal metastasis (Pu2009<u20090.001). On multivariable analysis, overall survival was significantly associated with histology of the tumour (Pu2009=u20090.019) and complete resection (Pu2009=u20090.047), and there was a trend towards significance (Pu2009=u20090.052) in the association between overall survival and nodal involvement.nnnCONCLUSIONSnLymph node metastasis in low-grade, early stage thymic tumours is a rare phenomenon. However, it is not uncommon in tumours with a higher stage or a higher histological grade, especially in neuroendocrine thymic tumours. Nodal involvement as well as tumour invasion and histological grade may denote worse prognosis. Lymph node dissection may be warranted in selected high-risk patients.

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.

The application of postoperative chemotherapy in thymic tumors and its prognostic effect

BACKGROUNDnTo study the role of postoperative chemotherapy and its prognostic effect in Masaoka-Koga stage III and IV thymic tumors.nnnMETHODSnBetween 1994 and 2012, 1,700 patients with thymic tumors who underwent surgery without neoadjuvant therapy were enrolled for the study. Among them, 665 patients in Masaoka-Koga stage III and IV were further analyzed to evaluate the clinical value of postoperative chemotherapy. The Kaplan-Meier method was used to obtain the survival curve of the patients divided into different subgroups, and the Cox regression analysis was used to make multivariate analysis on the factors affecting prognosis. A Propensity-Matched Study was used to evaluate the clinical value of chemotherapy.nnnRESULTSnTwo-hundred and twenty-one patients were treated with postoperative chemotherapy, while the rest 444 cases were not. The two groups showed significant differences (P<0.05) regarding the incidence of myasthenia gravis, World Health Organization (WHO) histological subtypes, pathological staging, resection status and the use of postoperative radiotherapy. WHO type C tumors, incomplete resection, and postoperative radiotherapy were significantly related to increased recurrence and worse survival (P<0.05). Five-year and 10-year disease free survivals (DFS) and recurrence rates in patients who underwent surgery followed by postoperative chemotherapy were 51% and 30%, 46% and 68%, comparing with 73% and 58%, 26% and 40% in patients who had no adjuvant chemotherapy after surgery (P=0.001, P=0.001, respectively). In propensity-matched study, 158 pairs of patients with or without postoperative chemotherapy (316 patients in total) were selected and compared accordingly. Similar 5-year survival rates were detected between the two groups (P=0.332).nnnCONCLUSIONSnPathologically higher grade histology, incomplete resection, and postoperative radiotherapy were found to be associated with worse outcomes in advanced stage thymic tumors. At present, there is no evidence to show that postoperative chemotherapy may help improve prognosis in patients with Masaoka-Koga stage III and IV thymic tumors.

Lack of epidermal growth factor receptor gene mutations in exons 19 and 21 in primary lymphoepithelioma-like carcinoma of the lung

Primary lymphoepithelioma‐like carcinoma (LELC) of the lung is uncommon in non‐small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) targeted therapy has been applied in advanced common NSCLC. Whether EGFR‐targeted therapy is also suitable for LELC of the lung remains unclear. As we know, EGFR gene mutation is a predictive factor. Therefore, EGFR gene mutations in exons 19 and 21 in Chinese patients with LELC of the lung were investigated.

Chinese expert consensus on mediastinal lymph node dissection in esophagectomy for esophageal cancer (2017 edition)

Esophageal cancer is an aggressive malignancy and a major cause of cancer-related deaths globally. In 2012, about 460,000 new cases of esophageal cancer were diagnosed worldwide, with 400,000 deaths attributed to the disease (1).