Long-Term Survival After Surgical Treatment of Thymic Carcinoma: A Retrospective Analysis from the Chinese Alliance for Research of Thymoma Database.

BACKGROUND: Thymic carcinoma is a type of rare and highly malignant tumor that originates from the thymic epithelium. Treatment and prognosis of thymic carcinoma remain controversial. We retrospectively analyzed survival data from a large-sample multicenter database in China. METHODS: The Chinese Alliance for Research of Thymoma constructed a retrospective database of patients with thymic epithelial tumors, which enrolled 1930 patients from January 1996 to August 2013, including 329 with thymic carcinomas. In this study, we analyzed clinical, pathologic, and treatment information, measured long-term survival rates, and identified relevant prognostic factors. RESULTS: Of 329 patients, R0 resection was performed in 211 (57.7 %), R1 in 34 (9.2 %), and R2 in 84 (22.5 %).The 3-, 5-, and 10-year survival rates were 78.3, 67.1, and 47.9 %, respectively. In univariate analysis, early Masaoka-Koga stage, R0 resection, and postoperative radiotherapy were associated with better overall survival.Early Masaoka-Koga stage and postoperative radiotherapy were also associated with disease-free survival. In multivariate analyses, R0 resection, Masaoka-Koga stage, and postoperative radiotherapy were significant prognostic factors of survival. CONCLUSIONS: Complete resection is the preferred primary treatment for thymic carcinoma. R0 resection, early Masaoka-Koga stage, and postoperative radiotherapy are significant predictors of improved survival.

[Comparison of surgical approaches for thymic disorders: feasibility of VATS thymectomy and comparison with small incision and median sternotomy].

OBJECTIVES: To evaluate the feasibility and safety of video-assisted thoracoscopic surgery (VATS), and to compare surgical results of VATS with standard median sternotomy (MS) and other minimal invasive approaches through various small incisions (SI). METHODS: Totally 111 patients underwent surgery for thymic disorders (maximun diameter ≤ 5 cm, clinical stage I-II for thymic tumors) during March 2010 to June 2012 was retrospectively reviewed. There were 46 male and 65 female patients with a mean age of (51 ± 15) years.Resection via VATS was carried out in 47 patients, via SI in 26 patients, and via MS in 38 patients. Demographic characteristics, operation time, number and cause of conversion, blood loss during operation, duration and amount of chest tube drainage, transfusion, morbidity, and length of hospital stay (LHS) were compared between the three groups. RESULTS: Of the 111 patients, 79 patients had thymic epithelia tumors (stage I 32 patients, stage II 39 patients, stage III 8 patients), 31 patients had benign cysts and 1 patient had tuberculosis.In the VATS group, there were 3 conversions among 38 patients through right-side approach, and 4 conversions among 9 patients through left-side approach. The causes for conversion included dense pleura adhesion, invasion of tumor into adjacent structures (pericardium, lung, or great vessels), and injury of the left inominate vein. There was no significant difference in operative time, blood loss or transfusion during operation, duration or amount of postoperative chest tube drainage among the 3 groups (P > 0.05). Average LHS was significantly shorter in the VATS group (5.7 ± 1.7) days than in the SI group (7.5 ± 2.2) days and the MS group (8.2 ± 1.9) days (F = 3.759, P = 0.002). Total thymectomy was performed in 74 patients, 25 patients (53.2%, 25/47) in VATS group, 11 patients (42.3%, 11/26) in SI group, and 38 patients (100%, 38/38) in MS group. The reset of the patients received tumor resection and partial thymectomy. Among all the subgroups, LHS was the shortest in VATS total thymectomy patients (5.0 ± 1.4) days (F = 5.844, P = 0.001). There was no perioperative mortality. The only major morbidity was a postoperative bleeding necessitating reintervention in SI group. CONCLUSIONS: VATS for benign thymic lesions and early-stage thymic tumors is safe and feasible.It is associated with shorter hospital stay compared with other minimal invasive approaches or standard sternotomy.

[Recurrence pattern of histological node-negative squamous cell carcinoma of the thoracic esophagus after extended radical esophagectomy with lymphadenectomy].

OBJECTIVE: To analyze the clinical and pathologic influencing factors of early recurrence in patients with histological node-negative (pN0 stage) esophageal squamous cell carcinoma after radical esophagectomy. METHODS: A retrospective study on 112 consecutive pN0 stage esophageal squamous cell carcinoma patients who underwent esophagectomy with lymphadenectomy by the same surgical team from January 2004 to December 2010. There were 92 male and 20 female patients, aging from 36 to 80 years with a mean age of 60.3 years. The Cox proportional hazards model was used to determine the independent risk factors for recurrence within 3 years after the operation. RESULTS: Recurrence was recognized in 45 patients (40.2%) within 3 years after operation. The median time to tumor recurrence was 17.4 months. Locoregional recurrence was found in 38 patients (33.9%), and hematogenous metastasis in 7 patients (6.3%). Recurrence closely correlated with tumor location, grade of differentiation, pT stage and pathologic stage (χ(2) = 6.380 to 18.837, P < 0.05). The Cox multivariate analysis showed that tumor location (RR = 1.092, P = 0.049) and pT3-4a stage (RR = 3.296, P = 0.017) were independent risk factors for postoperative locoregional recurrence. CONCLUSIONS: The most common recurrence pattern of patients with pN0 esophageal squamous cell carcinoma would develop recurrence within 3 years after operation is locoregional recurrence. Upper/middle thoracic location and pT3-4a stage are independent risk factors for locoregional recurrence of pN0 esophageal squamous cell carcinoma after operation.

Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas.

Thymic carcinoma (TC) is the most aggressive thymic epithelial neoplasm. TC patients with microsatellite instability, whole-genome doubling, or alternative tumor-specific antigens from gene fusion are most likely to benefit from immunotherapies. However, due to the rarity of this disease, how to prioritize the putative biomarkers and what constitutes an optimal treatment regimen remains largely unknown. Therefore, we integrated genomic and transcriptomic analyses from TC patients and revealed that frameshift indels in KMT2C and CYLD frequently produce neoantigens. Moreover, a median of 3 fusion-derived neoantigens was predicted across affected patients, especially the CATSPERB-TC2N neoantigens that were recurrently predicted in TC patients. Lastly, potentially actionable alterations with early levels of evidence were uncovered and could be used for designing clinical trials. In summary, this study shed light on our understanding of tumorigenesis and presented new avenues for molecular characterization and immunotherapy in TC.

Increased expression of the long non-coding RNA ANRIL promotes lung cancer cell metastasis and correlates with poor prognosis.

BACKGROUND: Emerging evidences indicate that dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression. LncRNA ANRIL has been shown to promote the progression of gastric cancer. However, the role of lncRNA ANRIL in human non-small cell lung cancer (NSCLC) remains unclear. METHODS: Expression of lncRNA ANRIL was analyzed in 87 NSCLC tissues and three lung cancer cell lines by quantitative real-time PCR (qRT-PCR). The correlation of lncRNA ANRIL with clinicopathological features and prognosis was analyzed. Suppression of lncRNA ANRIL using siRNA treatment was performed in order to explore its role in tumor progression. RESULTS: The expression level of lncRNA ANRIL was higher in NSCLC tissues and lung cancer cells than in adjacent non-tumor tissues and normal human bronchial epithelial cells. Higher expression of lncRNA ANRIL in NSCLC tissues was associated with higher TNM stage and advanced lymph node metastasis. Patients with high lncRNA ANRIL expression had poorer overall survival compared with low lncRNA ANRIL group. Univariate and multivariate analyses suggested that high expression of lncRNA ANRIL was an independent poor prognostic indicator for NSCLC patients. Moreover, knockdown of lncRNA ANRIL expression could inhibit lung cancer cell proliferation, migration and invasion in vitro. CONCLUSIONS: Our results suggested that lncRNA ANRIL was a potential biomarker for NSCLC prognosis, and the dysregulation of lncRNA ANRIL may play an important role in NSCLC progression. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1707061287149690 .

Comparison of video-assisted thoracoscopic surgery and median sternotomy approaches for thymic tumor resections at a single institution.

PURPOSE: This study was designed to evaluate the feasibility and safety of video-assisted thoracoscopic surgery (VATS), and to compare the surgical results of VATS with the standard median sternotomy (MS) approach. MATERIALS AND METHODS: Between April 2010 and April 2012, the data of 245 patients who underwent thymectomy for thymic tumors were prospectively collected. Among them, 93 patients with clinical stage I-II disease were retrospectively reviewed. RESULTS: Resection was planned for VATS in 49 cases, and for MS in 44 cases. During operation, there were 3 conversions to open surgery because of local invasion (conversion to thoracotomy in 1 patient, and sternotomy in 2). No transfusion was required in any patient. There was no significant difference in duration or amount of postoperative chest tube drainage between the 2 groups (P>0.05). Operative time, blood loss during operation, average length of the intensive care unit stay, and length of hospital stay were significantly less in the VATS group than the MS group (P<0.05). There were no major perioperative complications or mortality. No recurrence was detected during a median follow-up of 27 months (range, 12 to 36 mo). CONCLUSIONS: VATS thymectomy for early-stage thymic tumors is safe and feasible. In comparison with standard MS, the VATS approach was associated with a shorter intensive care unit stay and hospital stay. Prospective randomized multi-institutional trials with long-term follow-up are needed to compare the oncological outcomes.

Clinical study on postoperative recurrence in patients with pN0 esophageal squamous cell carcinoma.

BACKGROUND: Despite increasingly radical surgery for esophageal carcinoma, many patients still develop tumor recurrence after operation. This study was designed to analyze the clinical and pathologic influencing factors of early recurrence in patients with histological node-negative (pN0 stage) esophageal squamous cell carcinoma (ESCC) after radical esophagectomy. METHODS: A retrospective study on 112 consecutive pN0 stage ESCC patients who underwent esophagectomy with lymphadenectomy by the same surgical team from January 2004 to December 2010. There were 92 male and 20 female patients, aging from 36 to 80 years with a mean age of 60.3 years. The Cox proportional hazards model was used to determine the independent risk factors for recurrence within 3 years after the operation. RESULTS: Recurrence was recognized in 45 patients (40.2%) within 3 years after operation. The median time to tumor recurrence was 17.4 months. Locoregional recurrence was found in 38 patients (33.9%) and hematogenous metastasis in 7 patients (6.3%). However, locoregional recurrence accounted for 84.4% of all relapse patients. Recurrence closely correlated with tumor location, grade of differentiation, primary tumor stage (pT) and pathologic stage (χ2 = 6.380 to 18.837, p < 0.05). The Cox multivariate analysis showed that upper/middle thoracic location (OR = 1.092, p = 0.049) and pT3-4a stage (OR = 3.296, p = 0.017) were independent risk factors for postoperative locoregional recurrence. CONCLUSION: Locoregional recurrence was the most common recurrence pattern of patients with pN0 ESCC within 3 years after operation. Upper/middle thoracic location and pT3-4a stage were independent risk factors for locoregional recurrence of pN0 ESCC after radical esophagectomy.

[Risk factors of recurrence and metastasis in pN1 stage squamous cell carcinoma of the thoracic esophagus after radical esophagectomy with lymphadenectomy].

OBJECTIVE: To analyze the clinical and pathologic risk factors of early recurrence in patients with pathological N1 (pN1) stage esophageal squamous cell carcinoma after radical esophagectomy. METHODS: A retrospective study was carried out on 95 consecutive pN1 stage esophageal squamous cell carcinoma patients undergoing esophagectomy with lymphadenectomy by the same surgical team from January 2004 to December 2010 was performed. The Cox proportional hazards model was used to determine the independent risk factors for recurrence and metastasis within 3 years after the operation. RESULTS: Recurrence was identified in 52 patients (54.7%) within 3 years after operation. Local recurrence was found in 42 patients (44.2%), and distant metastasis in 10 patients (10.5%). The Cox multivariate analysis showed that pT3-4a stage (RR=3.604, P=0.027), positive lymph node metastasis in two stations (RR=4.834, P=0.009) or two fields (RR=5.689, P=0.003), and postoperative adjuvant chemotherapy (RR=1.594, P=0.048) were independent risk factors for postoperative recurrence. CONCLUSIONS: Postoperative adjuvant chemotherapy can decrease the probability of postoperative recurrence and metastasis of pN1 esophageal squamous cell carcinoma. As for patients who are identified as multi-station or multi-field lymph node metastasis, preoperative induced therapy maybe further improve treatment outcomes.

Adenoid cystic carcinoma of the esophagus: report of two cases and review of the Chinese literature.

Squamous cell carcinoma is the major pathology type of esophageal cancer in China, where adenocarcinoma is rare and adenoid cystic carcinoma (ACC) is more rare comparing to the western countries. We report the surgical and pathologic findings of two cases of primary ACC of the esophagus, and review of the Chinese literature of this tumor. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1507582238843246.

Proteome analysis and tissue array for profiling protein markers associated with type B thymoma subclassification.

BACKGROUND: The prognostic relevance of World Health Organization (WHO) subtypes within type B thymomas is still controversial. Understanding of the molecular characteristics of the different histologic types of thymomas will provide meaningful information for diagnosis and therapeutic management in type B thymoma. METHODS: Proteins extracted from twelve type B thymoma tissue specimens (six type B1 and six type B2) were analyzed by two-dimensional electrophoresis (2-DE) coupled with MALDI-TOF-MS. Differentially expressed proteins were then assayed in sixty-nine type B thymoma tissues (including B1, B2 and B3) by tissue array analysis with immunohistochemistry staining. The relationship of their expression with clinicopathological parameters, such as tumor stage or WHO classification, was estimated by Spearman's Rank Correlation Test. RESULTS: Sixteen differentially expressed proteins between type B1 and B2 thymoma tissues were identified. The differential levels of ezrin and glutathione S-transferase pi (GSTP1) were validated using immunohistochemistry staining. A statistically significant difference was observed in the positive rate of ezrin expression between type B1 thymoma and type B3 thymoma (Z = -2.963, P < 0.01). Ezrin showed a tendency to be expressed in higher classification tumors from type B1 to B3. A statistical analysis demonstrated that type B2 and B3 tumors had significantly higher positive expression of GSTP1 than the B1 group (type B2 vs. B1: Z = -2.582, P = 0.01; type B3 vs. B1: Z = -4.012, P ≤ 0.001). The results also showed a strong correlation between GSTP1 and WHO type staging of B1 to B3 tumors (Spearman's correlation coefficient: 0.633, P ≤ 0.001). Statistical analysis showed that there was close correlation between GSTP1 and ezrin expression with the clinical stage (Spearman's correlation coefficients, ezrin: 0.481, P < 0.05; GSTP1: 0.484, P < 0.01). CONCLUSIONS: Differentially expressed proteins between type B1 and B2 thymoma tissues were analyzed by comparative proteomic analysis. The techniques of proteomic analysis and tissue array provide a potential tool for screening of key molecules in type B thymoma histological sub-classifications. The statistical analysis of ezrin and GSTP1 expression by immunohistochemistry, especially GSTP1, may be a useful approach for type B thymoma classification.

[Comparison of outcomes after surgery between adenocarcinoma of the esophagogastric junction and lower thoracic esophageal squamous cell cancer].

OBJECTIVE: To compare the differences in biological behavior and clinical features between adenocarcinoma of the esophagogastric junction (AEG) and lower thoracic esophageal squamous cell cancer (LESC), and to explore reasonable procedures for each cancer. METHODS: Clinical data of 111 patients with AEG and 126 patients with LESC who underwent surgery from January 2004 to April 2012 were retrospectively reviewed. Data pertaining to resection rate, lymph node metastasis, and postoperative complication rate were analyzed. RESULTS: The resection rate was 94.6% for AEG and 97.6% for LESC, and the difference was not statistically significant (P<0.05). The rate of lymph node metastasis in the mediastinum in patients with AEG was significantly lower [6.3%(7/111) vs. 32.5%(41/126), P<0.01], while the rate of lymph node metastasis in the abdomen was significantly higher [57.7%(64/111) vs. 34.1%(43/126), P<0.01]. The rate of lymph node metastasis in mediastinum of AEG was 12.5%(4/32) for Siewert I and 4.7%(3/64) for Siewert II, and there was no lymph node metastasis in Siewert III (n=15). For AEG patients who underwent trans-abdominal surgery, the rate of positive lymph node in the middle and lower mediastinum was significantly lower than trans-thoracic surgery [0/22 vs. 7.9% (7/89), P<0.05]. LESC via right thorax with two-field or three-field lymph node dissection was associated with a significantly higher rate of positive lymph node metastasis in the upper mediastinum than that of single incision via left thorax [17.9%(12/67) vs. 0/59, P<0.01]. The postoperative complication rates were 23.4%(26/111) and 27.0%(34/126) respectively, and the difference was not statistically significant(P>0.05). CONCLUSIONS: AEG and LESC show different lymph node metastasis pattern and should be operated differently. Lymphadenectomy in mid-lower mediastinum should be emphasized in Siewert I and Siewert II type cancers.

[Comparative study of perioperative complications and lymphadenectomy between minimally invasive esophagectomy and open procedure].

OBJECTIVE: To analyze the differences in perioperative morbidity and lymph node dissection between minimally invasive esophageal carcinoma resection and open procedure. METHODS: From January to December 2011, 72 patients with esophageal cancer underwent surgery. Thirty-four patients underwent video-assisted esophagectomy, and 38 underwent open procedure. In the minimally invasive group, there were 7 thoraco-laparoscopic cases, 16 thoracoscopic cases, and 11 laparoscopic cases. RESULTS: The early cases (T1-T2) were more common in the minimally invasive group than that in the open group [79.4%(27/34) vs. 55.3%(21/38), P<0.05]. The complication rate was 41.2%(11/34) in the open group and 42.1%(16/38) in the minimally invasive group, and the difference was not statistically significant (P>0.05). However, the functional complication in minimally invasive group was significantly lower than that in open group [2.9%(1/34) vs. 28.9%(11/38), P<0.01], while technical complications (anastomotic leak and recurrent laryngeal nerve injury) were significantly more common( 38.2% vs. 10.5%, P<0.05). Lymph node group number in minimally invasive group was comparable with the open group (9.1 vs. 11.2, P>0.05), but the number of node in minimally invasive group was significantly lower (13.5±5.9 vs. 17.8±5.2, P<0.05). When stratified by time period, early 17 cases were associated with similar technical complication rate with the late 17 cases (P>0.05), while thoracic lymph node group number, number of node, and positive node were improved in the late phase (all P>0.05). CONCLUSIONS: Minimally invasive esophagectomy reduces functional morbidity, while technical complication including anastomotic leak and recurrent laryngeal nerve injury may be increased. Endoscopic lymph node dissection may be comparable to open surgery.