Publications by authors named "Jiaqing Xiang"

86 Publications

Tectorigenin alleviates intrahepatic cholestasis by inhibiting hepatic inflammation and bile accumulation via activation of PPARγ.

Br J Pharmacol 2021 Mar 4. Epub 2021 Mar 4.

Department of Endocrinology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.

Background And Purpose: Increasing evidence suggests that human cholestasis is closely associated with the accumulation and activation of hepatic macrophages. Research indicates that activation of PPARγ exerts liver protective effects in cholestatic liver disease (CLD), particularly by ameliorating inflammation and fibrosis, thus limiting disease progression. However, existing PPARγ agonists, such as troglitazone and rosiglitazone, have significant side effects that prevent their clinical application in the treatment of CLD. In this study, we found that tectorigenin alleviates intrahepatic cholestasis in mice by activating PPARγ.

Experimental Approach: Wild-type mice were intragastrically administered α-naphthylisothiocyanate (ANIT) or fed a diet containing 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to simultaneously establish an experimental model of intrahepatic cholestasis and tectorigenin intervention, followed by determination of intrahepatic cholestasis and the mechanisms involved. In addition, PPARγ-deficient mice were administered ANIT and/or tectorigenin to determine whether tectorigenin exerts its liver protective effect by activating PPARγ.

Key Results: Treatment with tectorigenin alleviated intrahepatic cholestasis by inhibiting the recruitment and activation of hepatic macrophages and by promoting the expression of bile transporters via activation of PPARγ. Furthermore, tectorigenin increased expression of the bile salt export pump (BSEP) through enhanced PPARγ binding to the BSEP promoter. In PPARγ-deficient mice, the hepatoprotective effect of tectorigenin during cholestasis was blocked.

Conclusion And Implications: In conclusion, tectorigenin reduced the recruitment and activation of hepatic macrophages and enhanced the export of bile acids by activating PPARγ. Taken together, our results suggest that tectorigenin is a candidate compound for cholestasis treatment.
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http://dx.doi.org/10.1111/bph.15429DOI Listing
March 2021

Local therapy for oligometastatic esophageal squamous cell carcinoma: a prospective, randomized, Phase II clinical trial.

Future Oncol 2021 Apr 25;17(11):1285-1293. Epub 2021 Feb 25.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.

For patients with oligometastatic esophageal squamous cell carcinoma, the efficacy of local therapy is still controversial because of patient selection and lack of adequate controls in most studies. Here the authors design the ESO-Shanghai 13 trial, a prospective, multicenter, randomized, Phase II trial, to assess the impact of combined local therapy and systemic therapy on progression and survival compared with systemic therapy alone for patients with four or less metastases. A total of 102 patients will be recruited over 3 years from approximately five centers and randomized in a 1:1 ratio to receive either systemic therapy alone or systemic therapy and local therapy, such as radiation, surgery and thermal ablation. The primary endpoint is progression-free survival. The secondary endpoints are overall survival, local control, toxicity and quality of life. Clinical trial registration: NCT03904927 (ClinicalTrials.gov).
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http://dx.doi.org/10.2217/fon-2020-0873DOI Listing
April 2021

Impact of Lymph Node Dissection on Survival after Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: From the Results of NEOCRTEC5010, a Randomized Multicenter Study.

Ann Surg 2021 Feb 10. Epub 2021 Feb 10.

Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China Sun Yat-sen University Cancer Center, Guangzhou, China Cancer Hospital of Shantou University Medical College, Shantou, China Taizhou Hospital, Wenzhou Medical University, Taizhou, China Tianjin Medical University Cancer Hospital, Tianjin, China Sichuan Cancer Hospital & Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, China Zhejiang Cancer Hospital, Hangzhou, China Fudan University Shanghai Cancer Center, Shanghai, China The University of Hong Kong-Shenzhen Hospital, Hong Kong, China.

Objective: To clarify whether systemic lymph node dissection (LND) influences the safety of surgery and the survival of patients with locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (nCRT).

Summary Background Data: Prognostic impact of systemic lymphadenectomy during surgery after nCRT for ESCC is still uncertain and requires clarification.

Methods: This is a secondary analysis of NEOCRTEC5010 trial which compared nCRT followed by surgery versus surgery alone for locally advanced ESCC. Relationship between number of LND and perioperative, recurrence and survival outcomes were analyzed in the nCRT group.

Results: Three-year overall survival was significantly better in the nCRT group than the S group (75.2% vs 61.5%; P=0.011). In the nCRT group, greater number of LND was associated with significantly better overall survival (HR, 0.358; P < 0.001) and disease-free survival (HR, 0.415; P=0.001), but without any negative impact on postoperative complications. Less LND (< 20 vs ≥ 20) was significantly associated with increased local recurrence (18.8% vs 5.2%, P=0.004) and total recurrence rates (41.2% vs 25.8%, P=0.027). Compared to patients with persistent nodal disease, significantly better survival was seen in patients with complete response and with LND ≥ 20, but not in those with LND < 20.

Conclusions: Systemic lymph node dissection does not increase surgical risks after nCRT in ESCC patients. And it is associated with better survival and local disease control. Therefore, systemic lymphadenectomy should still be considered as an integrated part of surgery after nCRT for ESCC.
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http://dx.doi.org/10.1097/SLA.0000000000004798DOI Listing
February 2021

Preoperative Folate Receptor-Positive Circulating Tumor Cell Level Is a Prognostic Factor of Long Term Outcome in Non-Small Cell Lung Cancer Patients.

Front Oncol 2020 28;10:621435. Epub 2021 Jan 28.

Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Surgical resection is often the preferred treatment for non-small cell lung cancer (NSCLC) patients. Predictive biomarkers after surgery can help monitoring and treating patients promptly, so as to improve the clinical outcome. In this study, we evaluated one potential candidate biomarker, the folate receptor-positive circulating tumor cell (FRCTC), by investigating its prognostic and predictive significance in NSCLC patients who underwent surgery.

Methods: In this prospective, observational study, we enrolled NSCLC patients who were eligible to receive surgery. Prior to operation, peripheral blood was collected from each patient for an FRCTC analysis. FRCTCs were isolated by negative enrichment using immunomagnetic beads to deplete leukocytes and then quantitatively detected by a ligand-targeted polymerase chain reaction (PCR) method. These patients were then given standard care and were actively followed up for seven years. At the end of the follow-up period, the association between the FRCTC level and the prognosis in these patients was evaluated.

Results: Overall, preoperative FRCTC level was not significantly different among NSCLC patients with adenocarcinoma or non-adenocarcinoma subtypes ( = 0.24). However, between patients with low- and high-risk pathological adenocarcinoma subtypes, the preoperative FRCTC level was significantly different ( = 0.028). Further, patients with lower preoperative FRCTC level had longer relapse-free survival (RFS) and overall survival (OS) than those with higher preoperative FRCTC level (RFS: not reached vs. 33.3 months, = 0.018; OS: not reached vs. 72.0 months, = 0.13). In a multivariate COX regression analysis, FRCTC level (HR = 4.10; 95% CI, 1.23-13.64; =0.022) and pathological stage (HR = 3.16; 95% CI, 1.79-10.14; = 0.0011) were independent prognostic factors of RFS. Moreover, FRCTC level together with adenocarcinoma subtypes provided additional information on risk for disease recurrence compared with FRCTC or adenocarcinoma subtype alone.

Conclusion: Our study demonstrated that the preoperative FRCTC level was a potential predictor for the prognosis of NSCLC patients underwent surgery. Further, when preoperative FRCTC level is considered together with primary tumor proliferation characteristics, its prognostic value supplements that of these conventional pathological features.
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http://dx.doi.org/10.3389/fonc.2020.621435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876466PMC
January 2021

Immunoscore Signature Predicts Postoperative Survival and Adjuvant Chemotherapeutic Benefits in Esophageal Squamous Cell Carcinoma.

Cancer Manag Res 2020 15;12:12885-12894. Epub 2020 Dec 15.

Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

Objective: The aim of this study was to construct the immunoscore (IS) to facilitate the prediction of postoperative survival and benefit from adjuvant chemotherapy (ACT) in esophageal squamous cell carcinoma (ESCC).

Methods: A total of 249 patients who received radical esophagectomy at Fudan University Shanghai Cancer Center were divided into training set and testing set. Eighty-nine patients with ESCC from TCGA database were enrolled into the validation set. Myeloid cells in tumor microenvironment were evaluated by immunohistochemistry or CIBERSORT, and then were included into a LASSO Cox regression model to construct the immunoscore. The predictive value of the immunoscore for prognosis after surgery or ACT was analyzed.

Results: The immunoscore was constructed by four types of myeloid cells including macrophages, neutrophils, mast cells, and dendritic cells and was demonstrated as IS=2^(0.527719*Mφ -0.2604269*MC-0.4812935*DC-0.4519706*Neu). The overall survival was significantly different between two immunotypes, which were divided according to the immunoscore, in all sets (<0.001, =0.005, and =0.002, respectively). Immunotype A was identified as an independent predictor for survival benefit in all three sets (HR=2.068, =0.005; HR=2.028, =0.007; HR=6.474, =0.007; respectively). In patients who received ACT, immunotype A was significantly related to longer overall survival both in the training set (<0.001) and in the testing set (=0.011). The nomogram based on immunotype and other clinicopathological factors showed good efficiency of predicting response to ACT. Finally, several important cytokines and pathways were highly enriched in immunoscore A subgroup.

Conclusion: The immunoscore was an effective prognostic predictor in ESCC for patients undergoing surgical resection and receiving ACT.
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http://dx.doi.org/10.2147/CMAR.S279684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751312PMC
December 2020

Esophagectomy With Three-Field Versus Two-Field Lymphadenectomy for Middle and Lower Thoracic Esophageal Cancer: Long-Term Outcomes of a Randomized Clinical Trial.

J Thorac Oncol 2021 02 8;16(2):310-317. Epub 2020 Dec 8.

Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Institute of Thoracic Oncology, Fudan University, Shanghai, People's Republic of China. Electronic address:

Introduction: The optimal extent of lymphadenectomy during esophagectomy remains unclear. In this trial, we aim to clarify whether three-field (cervical-thoracic-abdominal) lymphadenectomy improved patient survival over two-field (thoracic-abdominal) lymphadenectomy for esophageal cancer.

Methods: Between March 2013 and November 2016, a total of 400 patients with middle and lower thoracic esophageal cancer were included and randomly assigned to undergo esophagectomy with either three- or two-field lymphadenectomy at a 1:1 ratio. Analyses were done according to the intention-to-treat principle. The primary end point was overall survival (OS), calculated from the date of randomization to the date of death from any cause.

Results: Demographic characteristics were similar in the two arms. The median follow-up time was 55 months (95% confidence interval [CI]: 52-58). OS (hazard ratio [HR] = 1.019, 95% CI: 0.727-1.428, p = 0.912) and the disease-free survival (DFS) (HR = 0.868, 95% CI: 0.636-1.184, p = 0.371) were comparable between the two arms. The cumulative 5-year OS was 63% in the three-field arm, as compared with 63% in the two-field arm; 5-year DFS was 59% and 53%, respectively. On the basis of whether the patients had mediastinal or abdominal lymph node metastasis or not, OS was also comparable between the two arms. In this cohort, only advanced tumor stage (pathologic TNM stages III-IV) was identified as the risk factor associated with reduced OS (HR = 3.330, 95% CI: 2.140-5.183, p < 0.001).

Conclusions: For patients with middle and lower thoracic esophageal cancer, there was no improvement in OS or DFS after esophagectomy with three-field lymphadenectomy over two-field lymphadenectomy.
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http://dx.doi.org/10.1016/j.jtho.2020.10.157DOI Listing
February 2021

Is Tc bone scintigraphy necessary in the preoperative workup for patients with cT1N0 subsolid lung cancer? A prospective multicenter cohort study.

Thorac Cancer 2021 02 19;12(4):415-419. Epub 2020 Nov 19.

Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Tc bone scintigraphy (BS) is still the most common approach for the evaluation of bone metastasis in China. The purpose of this study was to investigate the necessity of BS as part of a routine preoperative workup for patients with cT1N0 subsolid lung cancer.

Methods: This was a prospective multicenter clinical trial (NCT03689439). Patients with cT1N0 subsolid nodules who were candidates for surgical resection were consecutively enrolled into the study. BS was performed preoperatively. The surgical plan could be changed if a positive result was detected. The primary endpoint was the incidence rate of the surgical plan being changed because of positive BS results. The secondary endpoint was the rate of positive BS findings and the rate of related complications.

Results: From November 2018 to July 2019, 691 patients were enrolled into the study. None of the patients had positive BS results and no surgical plans were changed by BS findings. There were 222 male and 469 female patients. The average age was 54.8 ± 3.7 years old. The average tumor diameter was 14.9 ± 4.2 mm. There were 282 patients with pure GGO nodules and 409 with part-solid nodules. A total of 470 patients had a single nodule, while 221 patients had multifocal lesions. The number of patients whose pathological diagnosis was invasive adenocarcinoma, minimally invasive adenocarcinoma, adenocarcinoma in situ and mucinous adenocarcinoma was 357, 293, 32 and nine, respectively. The number of patients who underwent lobectomy, segmentectomy and wedge resection was 234, 199 and 258, respectively.

Conclusions: Tc bone scintigraphy is unnecessary in the preoperative workup for patients with cT1N0 subsolid lung cancer.

Key Points: SIGNIFICANT FINDINGS OF THE STUDY: In this prospective study of 691 patients with cT1N0 subsolid lung cancer, no surgical plans were affected by positive bone scan findings.

What This Study Adds: We suggest physicians consider canceling BS from preoperative workup for cT1 subsolid lung cancer patients. Clinical trial registry number: NCT03689439.
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http://dx.doi.org/10.1111/1759-7714.13752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882389PMC
February 2021

Impact of post-operative serum albumin level on anastomotic leakage after transthoracic oesophagectomy for oesophageal squamous cell carcinoma.

ANZ J Surg 2021 01 5;91(1-2):E7-E13. Epub 2020 Nov 5.

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: The correlation of post-operative serum albumin level with the occurrence of anastomotic leakage (AL) in oesophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to evaluate the impact of post-operative serum albumin level on AL after transthoracic oesophagectomy.

Methods: Patients with ESCC who underwent transthoracic oesophagectomy between 2013 and 2017 in Fudan University Shanghai Cancer Center were included. The correlation of post-operative serum albumin level with the occurrence and short-term outcomes of AL was analysed.

Results: Patients with serum albumin level of <35 g/L on the first post-operative day were identified with higher frequency of AL in the whole study population (10.3% versus 6.1%; P < 0.001), intrathoracic anastomosis subgroup (7.1% versus 3.9%; P = 0.002) and cervical anastomosis subgroup (24.1% versus 16.0%; P = 0.042). Multivariate analysis showed that low albumin level was an independent risk factor of AL in the overall population (odds ratio (OR) 1.842; P < 0.001), intrathoracic anastomosis subgroup (OR 1.815; P = 0.006) and cervical anastomosis subgroup (OR 1.946; P = 0.013). In patients with AL, low albumin level was associated with poorer short-term outcomes. For patients with low albumin level on the first post-operative day, the probability of AL was significantly reduced if the level in the first post-operative week was improved to the normal range (5.9% versus 14.9%; P < 0.001).

Conclusion: Serum albumin level on the first post-operative day was an independent predictor of AL in patients with ESCC receiving transthoracic oesophagectomy. Increase of albumin level to the normal range post-operatively could reduce the risk of AL.
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http://dx.doi.org/10.1111/ans.16406DOI Listing
January 2021

Recurrence patterns after neoadjuvant chemoradiotherapy compared with surgery alone in oesophageal squamous cell carcinoma: results from the multicenter phase III trial NEOCRTEC5010.

Eur J Cancer 2020 10 30;138:113-121. Epub 2020 Aug 30.

State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address:

Background: The aim of this study was to compare recurrence patterns and prognostic factors for developing recurrences in patients with oesophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiotherapy (CRT) followed by surgery or surgery alone from a multicenter phase III trial NEOCRTEC5010.

Patients And Methods: Patients with locally advanced ESCC were randomly assigned in a 1:1 ratio to receive neoadjuvant CRT plus surgery (CRT + S group) or surgery alone (S group). CRT consisted of two cycles of vinorelbine and cisplatin with concurrent radiotherapy of 40.0 Gy in 20 fractions. Recurrence patterns, sites, frequency, and timing and potential prognostic factors were compared.

Results: Of the 451 patients enrolled from 2007 to 2014, 411 patients who underwent resection were analysed. After a median follow-up of 51.9 months, 62 patients (33.7%) in the CRT + S group versus 104 patients (45.8%) in the S group experienced recurrences (P = 0.013). The CRT + S group demonstrated a significantly better locoregional failure-free survival (P = 0.012) and a more favourable distant metastasis-free survival (P = 0.028) than the S group. Recurrences occurred earlier in the S group (P = 0.053), and late relapses were much more frequent in the CRT + S group (P = 0.029). On multivariate analysis, R1 resection and surgery alone were adverse factors for developing locoregional recurrences, whereas R1 resection was the only independent factor associated with distant metastases.

Conclusions: The neoadjuvant CRT regimen was associated with significantly reduced locoregional and distant recurrences compared with surgery alone. Recurrence patterns, sites and frequency were different between groups. TRIAL REGISTRATION CLINICALTRIALS.

Gov Identifier: NCT01216527.
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http://dx.doi.org/10.1016/j.ejca.2020.08.002DOI Listing
October 2020

Evolutionary Action Score of TP53 Enhances the Prognostic Prediction for Stage I Lung Adenocarcinoma.

Semin Thorac Cardiovasc Surg 2021 Spring;33(1):221-229. Epub 2020 May 23.

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Institute of Thoracic Oncology, Fudan University, Shanghai, China; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address:

Stage I lung adenocarcinoma usually has a good prognosis after surgery. However, some patients do suffer disease recurrence during follow-up. Here, we report the prognostic value of evolutionary action score of TP53, which calculates the functional prediction of TP53, in patients with stage I lung adenocarcinoma. From January 2011 to August 2013, 83 patients with a complete follow-up history (36 with a disease recurrence and 47 without recurrence during follow-up) who were pathologically confirmed stage I lung adenocarcinoma were included. Whole-exome sequencing were performed on those paired tumor-normal specimens. Evolutionary action score of TP53 (EAp53) was calculated and patients were divided into groups according to their TP53 mutational status. Tumor mutational burden and survival analyses were performed to assess the prognostic value of EAp53. TP53 mutation was identified in 31 patients (37.3%). Of them, 11 were high-risk point mutations, 9 were low-risk point mutations, and 11 were truncating mutations. The high-risk group showed a poorer recurrence-free survival compared with the low-risk group (P = 0.046) and the wild-type group (P = 0.007). In multivariable analysis, the high-risk/truncating group showed a poorer recurrence-free survival (P = 0.007) and overall survival (P = 0.009) compared with the low-risk/wild-type group. Moreover, tumor mutational burden was higher in the high-risk/truncating group (P < 0.001). EAp53 is of prognostic value in patients with stage I lung adenocarcinoma. The mutational type of TP53 should be paid attention to when predicting the prognosis of patients with stage I lung adenocarcinoma.
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http://dx.doi.org/10.1053/j.semtcvs.2020.04.005DOI Listing
May 2020

EGFR-mutant lung adenocarcinoma harboring co-mutational tumor suppressor genes predicts poor prognosis.

J Cancer Res Clin Oncol 2020 Jul 2;146(7):1781-1789. Epub 2020 May 2.

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.

Introduction: EGFR mutations occur most frequently in patients with lung adenocarcinoma in East Asia. However, the prognostic and therapeutic impact of co-mutational status of EGFR and tumor suppressor genes is not fully understood. This study aims to provide a deeper understanding of lung adenocarcinoma patients with co-mutation of EGFR and tumor suppressor genes.

Methods: From November 2009 to May 2016, 675 patients with lung adenocarcinoma who underwent complete surgery were included in this study. Samples were collected and pathologically examined. Whole-exome sequencing was performed on 197 samples, while direct sequencing of major driver genes, including EGFR, KRAS, ERBB2 and BRAF and Ion-torrent targeted sequencing of tumor suppressor genes, including TP53, KEAP1, MGA, NF1, RB1, SMARCA4 and STK11, were performed on 478 samples. Tumor mutational burden was calculated and survival analyses were performed.

Results: The frequency of EGFR and TP53 mutation was 409 (60.6%) and 215 (31.9%), respectively. Co-mutation of EGFR and TP53 occured in 151 patients (22.4%), while co-mutation of EGFR and at least one tumor suppressor gene occured in 184 patients (27.3%). Compared with patients with only EGFR mutations, patients with co-mutations of EGFR and TP53 had a higher tumor mutational burden (p = 0.007) and worse recurrence-free survival (p = 0.010), while patients with co-mutations of EGFR and at least one tumor suppressor gene had a higher tumor mutational burden (p = 0.007), worse recurrence-free survival (p = 0.016) and worse overall survival (p = 0.018).

Conclusions: Lung adenocarcinoma patients harboring EGFR and co-mutational tumor suppressor genes should be regarded as a unique subgroup.
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http://dx.doi.org/10.1007/s00432-020-03237-3DOI Listing
July 2020

Aging Attenuates Cardiac Contractility and Affects Therapeutic Consequences for Myocardial Infarction.

Aging Dis 2020 Apr 9;11(2):365-376. Epub 2020 Mar 9.

1Department of Pathophysiology, Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Guangdong, China.

Cardiac function of the human heart changes with age. The age-related change of systolic function is subtle under normal conditions, but abrupt under stress or in a pathogenesis state. Aging decreases the cardiac tolerance to stress and increases susceptibility to ischemia, which caused by aging-induced Ca transient impairment and metabolic dysfunction. The changes of contractility proteins and the relative molecules are in a non-linear fashion. Specifically, the expression and activation of cMLCK increase first then fall during ischemia and reperfusion (I/R). This change is responsible for the nonmonotonic contractility alteration in I/R which the underlying mechanism is still unclear. Contractility recovery in I/R is also attenuated by age. The age-related change in cardiac contractility influences the therapeutic effect and intervention timepoint. For most cardiac ischemia therapies, the therapeutic result in the elderly is not identical to the young. Anti-aging treatment has the potential to prevent the development of ischemic injury and improves cardiac function. In this review we discuss the mechanism underlying the contractility changes in the aged heart and age-induced ischemic injury. The potential mechanism underlying the increased susceptibility to ischemic injury in advanced age is highlighted. Furthermore, we discuss the effect of age and the administration time for intervention in cardiac ischemia therapies.
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http://dx.doi.org/10.14336/AD.2019.0522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069457PMC
April 2020

Does [18F] fluorodeoxyglucose-positron emission tomography/computed tomography have a role in cervical nodal staging for esophageal squamous cell carcinoma?

J Thorac Cardiovasc Surg 2020 Aug 11;160(2):544-550. Epub 2019 Dec 11.

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address:

Objective: Accurate nodal staging is crucial for esophageal cancer. A prospective study was performed to assess the value of [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for diagnosing cervical lymph node metastasis (LNM) of esophageal squamous cell carcinoma.

Methods: From June 2018 to November 2018, 110 patients with resectable esophageal cancer were prospectively enrolled. Esophagectomy with 3-field lymphadenectomy was performed after FDG-PET/CT scanning. The primary end point was cervical LNM determined via postoperative histologic examination. The sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy (AC) of FDG-PET/CT for the assessment of LNM were determined using histologic results as reference standards.

Results: Positive lymph nodes as determined via FDG-PET/CT were detected in 61 patients (55.5%), of whom 13 (11.8%) had positive cervical lymph nodes. After surgery, 59 patients (53.6%) exhibited pathologic LNM, of whom 20 (18.2%) had cervical LNM. SE, SP, PPV, NPV, and AC were 65.6%, 61.2%, 67.8%, 58.8%, and 63.6%, respectively, with regards to diagnosing overall LNM, and were 45.0%, 95.6%, 69.2%, 88.7%, and 86.4%, respectively, for diagnosing cervical LNM. Of the 110 patients, 90 underwent both FDG-PET/CT scanning and ultrasonography in the neck, and there were no significant differences in SE, SP, PPV, NPV, or AC with respect to cervical LNM diagnosis between FDG-PET/CT and ultrasonography.

Conclusions: For cervical LNM of esophageal squamous cell carcinoma, FDG-PET/CT scanning exhibited high specificity but low sensitivity, suggesting that it is of limited value for this purpose.
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http://dx.doi.org/10.1016/j.jtcvs.2019.11.046DOI Listing
August 2020

Imaging Features Suggestive of Multiple Primary Lung Adenocarcinomas.

Ann Surg Oncol 2020 Jun 20;27(6):2061-2070. Epub 2019 Dec 20.

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: The tumor-node-metastasis classification system has proposed that lung cancers presenting as multifocal ground-glass nodules (multi-GGN) on computed tomography scan should be staged as multiple primaries instead of intrapulmonary metastases. However, the problem still exists for those synchronous multiple lung adenocarcinomas (SMLA) involving solid lesions. This study aimed to explore the distinct features of SMLA to better define the diagnosis and staging of this disease.

Methods: Between 2008 and 2016, consecutive patients with complete resection of SMLA were prospectively enrolled in the study. The patients were divided into three groups based on CT images as follows: multi-GGN, one solid nodule plus one or more GGNs (solid-GGN), and multiple solid lesions with or without GGN (multi-solid). Clinicopathologic features and survival outcomes were compared between these groups. Multivariate Cox proportional hazards analyses using bootstrap internal validation were performed to identify independent predictors for recurrence-free survival (RFS) and overall survival (OS).

Results: Of the 695 patients who met the inclusion criteria, 486 (69.9%) presented with multi-GGN tumor, 124 (17.9%) with solid-GGN tumor, and 85 (12.2%) with multi-solid tumor. The three groups had distinguished clinicopathologic features of gender, smoking history, nodal metastases, tumor size, subtype, and location (all P < 0.001). Multivariate analyses demonstrated that multi-solid tumor was an independent predictor for both decreased RFS [hazard ratio (HR) 2.941; 95% confidence interval (CI) 1.07-8.08; P = 0.036] and poor OS (HR 6.13; 95% CI 1.15-32.63; P = 0.034), but neither RFS (P = 0.384) nor OS (P = 0.811) differed between solid-GGN and multi-GGN tumors.

Conclusions: Both multi-GGN and solid-GGN tumors should be staged as multiple primaries, whereas multi-solid tumor was indicated to be advanced disease.
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http://dx.doi.org/10.1245/s10434-019-08109-wDOI Listing
June 2020

Prognostic Impact of Postoperative Lymph Node Metastases After Neoadjuvant Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of Esophagus: From the Results of NEOCRTEC5010, a Randomized Multicenter Study.

Ann Surg 2019 Dec 17. Epub 2019 Dec 17.

Sichuan Cancer Hospital & Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, China.

Objective: To determine the prognostic impact of pathologic lymph node (LN) status and investigate risk factors of recurrence in esophageal squamous cell carcinoma (ESCC) patients with pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT).

Summary Background Data: There are no large-scale prospective study data regarding ypN status and recurrence after pCR in ESCC patients receiving NCRT.

Methods: The NEOCRTEC5010 trial was a prospective multicenter trial that compared the survival and safety of NCRT plus surgery (S) with S in patients with locally advanced ESCC. The relationships between survival and cN, pN, and ypN status were assessed. Potential prognostic factors in patients with ypN+ and pCR were identified.

Results: A total of 389 ESCC patients (NCRT: 182; S: 207) were included. Patients with pN+ in the S group and ypN+ in the NCRT group had decreased overall survival (OS) and disease-free survival (DFS) compared with pN0 and ypN0 patients, respectively. Partial response at the primary site [hazard ratio (HR), 2.09] and stable disease in the LNs (HR, 3.26) were independent risk factors for lower DFS, but not OS. For patients with pCR, the recurrence rate was 13.9%. Patients with distant LN metastasis had a median OS and DFS of 16.1 months and 14.4 months, respectively. Failure to achieve the median total dose of chemotherapy was a significant risk factor of recurrence and metastasis after pCR (HR, 44.27).

Conclusions: Persistent pathologic LN metastasis after NCRT is a strong poor prognostic factor in ESCC. Additionally, pCR does not guarantee a cure; patients with pCR should undergo an active strategy of surveillance and adjuvant therapy.
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http://dx.doi.org/10.1097/SLA.0000000000003727DOI Listing
December 2019

Genomic and immune profiling of pre-invasive lung adenocarcinoma.

Nat Commun 2019 11 29;10(1):5472. Epub 2019 Nov 29.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.
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http://dx.doi.org/10.1038/s41467-019-13460-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884501PMC
November 2019

Distinct Prognostic Factors in Patients with Stage I Non-Small Cell Lung Cancer with Radiologic Part-Solid or Solid Lesions.

J Thorac Oncol 2019 12 19;14(12):2133-2142. Epub 2019 Aug 19.

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People's Republic of China. Electronic address:

Introduction: Recent studies have indicated that the presence of ground-glass opacity (GGO) components is associated with favorable survival. The purpose of this study was to reveal the prognostic value of GGO components and differences in prognostic factors for part-solid and solid lesions in invasive stage I NSCLC.

Methods: The cases of 2010 patients with completely resected invasive pathological stage I NSCLC were reviewed according to the eighth edition of the TNM classification. Patients were categorized into the pure-GGO, part-solid, and solid groups based on consolidation-to-tumor ratio. Cox multivariate proportional hazard analyses were conducted to identify independent prognostic factors in each group.

Results: Of the 2010 patients, 146 (7.3%) were in the pure-GGO group, 732 (36.4%) were in the part-solid group, and 1132 (56.3%) were in the solid group. Cox multivariate analyses revealed that GGO absence was a strong independent risk factor for worse recurrence-free survival (p < 0.001). For the pure-GGO group, there was no recurrence in spite of the invasive stage. For the part-solid group, visceral pleural invasion could not predict recurrence-free survival in general (p = 0.514) or in each tumor size group (for tumors size ≤1 cm, p = 0.664; for tumors size >1 to 2 cm, p = 0.456; for tumors size >2 to 3 cm, p = 0.900; and for tumors size >3 to 4 cm, p = 0.397). For the solid group, adenocarcinoma subtype was not a prognostic factor for recurrence-free survival in general (p = 0.162) or in each tumor size group (for tumors size ≤ 2 cm, p = 0.092; for tumors size >2 to 3 cm, p = 0.330; and for tumors size >3 to 4 cm, p = 0.885).

Conclusions: The presence of GGO components was a strong predictor in patients with invasive pathological stage I NSCLC. Risk factors were distinct in the part-solid and solid groups. There was no prognostic value of visceral pleural invasion in the part-solid group. Adenocarcinoma subtype did not have prognostic value in the solid group.
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http://dx.doi.org/10.1016/j.jtho.2019.08.002DOI Listing
December 2019

Role of IL-37 in Cardiovascular Disease Inflammation.

Can J Cardiol 2019 07 16;35(7):923-930. Epub 2019 Apr 16.

Department of Pathophysiology, Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, Guangdong, China. Electronic address:

Inflammation is closely related to the pathogenesis and prognosis of cardiovascular disease (CVD). Interleukin-37 (IL-37), an anti-inflammatory IL-1 family cytokine, shifts cytokine expression from pro- to anti-inflammation via regulation of macrophage polarization and lipid metabolism. In macrophages, IL-37 functions through both intracellular and extracellular pathways to regulate the activity of NF-kB and PTEN as well as the expression of cytokines, including IL-1β, IL-6, and IL-10. Moreover, IL-37 levels are increased in the serum of patients with heart failure, atherosclerosis, and acute coronary syndrome with no evidence of anti-inflammatory effects. However, transgenic overexpression of IL-37 improves cardiac infarct and attenuates atherosclerosis plaque expansion. Hence, it is worthwhile to investigate the precise mechanism and role of IL-37 in the pathogenesis of CVD, which may provide deeper understanding of the inflammatory response in this context. This review summarizes the regulatory role of IL-37 in systematic inflammation induced by CVD and highlights recent advancements in the clinical application of IL-37 as a therapeutic agent or biomarker for diagnosis of CVD.
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http://dx.doi.org/10.1016/j.cjca.2019.04.007DOI Listing
July 2019

Predicting the Value of Adjuvant Therapy in Esophageal Squamous Cell Carcinoma by Combining the Total Number of Examined Lymph Nodes with the Positive Lymph Node Ratio.

Ann Surg Oncol 2019 Aug 11;26(8):2367-2374. Epub 2019 Jun 11.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: The value of adjuvant therapy for esophageal squamous cell carcinoma (ESCC) has been controversial, at least partially due to the lack of efficient criteria for selecting suitable patients. This study aimed to explore the existence of parameters related to lymph node (LN) status that can predict the value of adjuvant therapy in ESCC.

Methods: The study included 298 patients with ESCC who had undergone radical esophagectomy with lymphadenectomy. Adjuvant therapy was defined as reception of adjuvant chemotherapy, radiotherapy, or chemoradiotherapy. For the study, LN ratio (LNR), total number of resected LNs (TLNs), and pN stage were selected for Cox regression analyses, including their correlations and prognostic values for survival. Log-rank tests were used to compare the survival rates of the patients with and without adjuvant therapy stratified by pN stage, TLNs, LNR, or their combinations.

Results: The independent prognostic factors for survival were TLNs, LNR, and pN stage. Whereas pN stage was significantly related to TLNs and LNR, TLNs were not correlated with LNR. The survival rates between the patients with and those without adjuvant therapy stratified by pN stage, TLNs, or LNR did not differ significantly. We used the median values of TLNs and LNR to group the patients into four groups. The patients in the group with fewer TLNs and higher LNR who had undergone adjuvant therapy showed a significantly better survival than those without adjuvant therapy (p = 0.030).

Conclusions: In contrast to TLNs, LNR, and pN stage as single factors, the combination of TLNs and LNR can predict the value of adjuvant therapy.
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http://dx.doi.org/10.1245/s10434-019-07489-3DOI Listing
August 2019

Outcomes comparison between neoadjuvant chemotherapy and adjuvant chemotherapy in stage IIIA non-small cell lung cancer patients.

J Thorac Dis 2019 Apr;11(4):1443-1455

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Background: A neoadjuvant chemotherapy (NCT) is a feasible second-option other than an adjuvant chemotherapy (ACT); however, no definite conclusions have been drawn about whether or not a NCT is associated with better clinical outcomes for IIIA non-small cell lung cancer (NSCLC) patients.

Methods: We reviewed 68 clinical IIIA NSCLC patients who received preoperative chemotherapy (NCT group), and 535 pathological IIIA NSCLC patients who received ACT after surgery (ACT group). After a 1:1 propensity score matching (PSM), we compared the relapse-free survival (RFS) and overall survival (OS) rates as the long-term clinical outcomes, and hospital stay, surgery duration, postoperative complications as the short-term clinical outcomes. To evaluate the predictive value of the NCT response, we also assessed the response evaluation criteria in solid tumors (RECIST) response to NCT.

Results: There was no significant difference in RFS or OS between the NCT group and ACT group (RFS: P=0.1138; OS: P=0.4234). On multivariate analysis, large cell lung carcinoma (P=0.0264), bilobectomy (P=0.0039) and clinical N2 stage (P=0.0309) were independent predictive factors of a worse OS. Short-term clinical outcomes including the hospital stay and postoperative complications had no statistically distinct difference between the ACT and NCT groups. Meanwhile, the OS of the partial response (PR) patients group was better than the stable disease/progressive disease (SD/PD) (P=0.0205) and ACT (P=0.0442) group, but none of the clinical features we tested was found to be a predictive factor for a PR response.

Conclusions: There was a non-significant difference between the long-term and short-term clinical outcomes of both NCT and ACT. The OS of PR patients was better than SD/PD and ACT, indicating that NCT response acts as a predictor for a higher long-term survival rate.
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http://dx.doi.org/10.21037/jtd.2019.03.42DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531706PMC
April 2019

A prognostic score system with lymph node ratio in stage IIIA-N2 NSCLC patients after surgery and adjuvant chemotherapy.

J Cancer Res Clin Oncol 2019 Aug 7;145(8):2115-2122. Epub 2019 Jun 7.

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.

Purpose: The survival of patients with IIIA-N2 non-small cell lung cancer after surgery followed by adjuvant chemotherapy is heterogeneous. The aim of this study is to form a prognostic system and a heat map method to visualize the overall survival rates in those patients.

Methods: Univariate and multivariate Cox hazards regression models and the associated Wald Chi square coefficient were used to form the prognostic score system. Recursive partitioning analysis was used to determine the cutoff values of lymph node ratio and prognostic score in SEER cohort and validated in FDUSCC cohort. Meanwhile, a heat map method was used to visualize the overall survival probabilities of 3, 5 and 10 years for individual patient of both cohorts.

Results: Lymph node ratio (with cutoff of 0.36) significantly correlates with overall survival of these patients. In addition, in patients with the same level of N2 disease, lymph node ratio still significantly affects survival. Also, after the multivariate analysis in SEER cohort, six factors were independent prognostic factors including age, sex, type of surgery, size, lymph node ratio and differentiation. A prognostic sore system with these factors (with cutoff of 12) was validated as a predictor for overall survival in FDUSCC cohort.

Conclusions: This prognostic score system including lymph node ratio can predict the survival rates of IIIA-N2 patient after surgery and post-operative chemotherapy. Lymph node ratio could be a useful supplementation in TNM stage classification for IIIA-N2 patients. The heat map method can visualize the predicted overall survival of an individual patient.
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http://dx.doi.org/10.1007/s00432-019-02952-wDOI Listing
August 2019

tRNA-based prognostic score in predicting survival outcomes of lung adenocarcinomas.

Int J Cancer 2019 10 21;145(7):1982-1990. Epub 2019 Mar 21.

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

As the most abundant noncoding RNA in cells, tRNA plays an important role in tumorigenesis and development. The report of tRNA on the pathogenesis of lung adenocarcinoma is rare. It is of great clinical significance to explore the relationship between tRNA expression and prognosis of lung adenocarcinoma. The expression level of tRNAs in lung adenocarcinoma tissues and paracarcinoma tissues was detected using a tRNA RT-qPCR array. A total of 104 lung adenocarcinomas were included in the analysis of the correlation between candidate tRNAs expression and prognosis. A tRNA-based prognostic model was constructed and validated using Cox proportional hazards regression. A nomogram was built to help clinicians develop treatment strategies. We screened a series of differentially expressed tRNAs between lung adenocarcinoma tissues and paracarcinoma tissues. Among these tRNAs, tRNA , tRNA , tRNA , mt-tRNA , mt-tRNA , tRNA , tRNA and tRNA were associated with the clinicopathological characteristics of lung adenocarcinoma. tRNA , mt-tRNA and tRNA were associated with cancer-specific survival. We constructed a prognostic model for lung adenocarcinoma using specific tRNA expression levels as reference factors. Multivariate analyses showed that tRNA-based prognostic score was a significant and important prognostic factor. The prognostic model based on the tRNAs expression signatures can help predict the prognosis of patients with lung adenocarcinoma.
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http://dx.doi.org/10.1002/ijc.32250DOI Listing
October 2019

Esophageal squamous cell carcinoma patients with positive lymph nodes benefit from extended radical lymphadenectomy.

J Thorac Cardiovasc Surg 2019 Mar 12;157(3):1275-1283.e1. Epub 2018 Dec 12.

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address:

Background: The usefulness of lymphadenectomy for advanced esophageal cancer is unclear. A post-hoc subgroup analysis involving a randomized controlled trial was performed to compare the long-term survival of patients with esophageal cancer and lymph nodes metastasis (LNM) after extended lymphadenectomy via the right thoracic approach with that of those undergoing limited lymphadenectomy via the left thoracic approach.

Methods: Between May 2010 and July 2012, 300 patients with thoracic esophageal cancer were randomized to undergo esophagectomy through either the right or left thoracic approach. Of these patients, 129 with esophageal squamous cell carcinoma and LNM by postoperative pathology were included in this analysis. Disease-free survival and overall survival (OS) were compared between the extended (n = 64) and limited (n = 65) lymphadenectomy groups after 5 years' follow-up. Cox regression analysis was used to identify the factors associated with OS.

Results: The 5-year disease-free survival rates were 40% and 26% in the extended and limited lymphadenectomy groups, respectively (hazard ratio [HR], 1.542; 95% confidence interval [CI], 1.018-2.335; P = .037), and the 5-year OS rates were 51% and 31%, respectively (HR, 1.719; 95% CI, 1.111-2.660; P = .013). The extended lymphadenectomy group had less locoregional recurrence (HR, 0.583; 95% CI, 0.375-0.908; P = .015) and delayed distant metastasis (HR, 1.407; 95% CI, 0.914-2.167; P = .115). Reduced OS was associated with limited lymphadenectomy, R1/2 resection margins, TNM stage IV, and lack of postoperative adjuvant therapy, as per the Cox regression analysis.

Conclusions: Improved long-term survival was observed in patients with esophageal squamous cell carcinoma and LNM after extended lymphadenectomy via the right thoracic approach.
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http://dx.doi.org/10.1016/j.jtcvs.2018.11.094DOI Listing
March 2019

A model based on endoscopic morphology of submucosal esophageal squamous cell carcinoma for determining risk of metastasis on lymph nodes.

J Thorac Dis 2018 Dec;10(12):6846-6853

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Background: It is important to identify patients with esophageal squamous cell carcinoma (ESCC) in T1b stage that are the least likely to metastasize on the lymph nodes, to undergo endoscopic resection, especially for the patients unfit for esophagectomy. The relationship between endoscopic morphology and frequency of nodal metastasis has never been well studied. The aims of the study were to investigate the predictive value of endoscopic morphology for lymphatic metastasis, and to develop a risk stratification model in submucosal (T1b) ESCC.

Methods: Pathologic variables of patients with T1b ESCC who underwent esophagectomy from 2006 through 2016 were collected and divided into training sets (patients between 2006 and 2011) and validation sets (patients between 2012 and 2016). The endoscopic morphology of the tumor was determined by analyzing endoscopic reports according to the Paris classification. The correlation between the clinicopathological factors and nodal metastasis was examined. A prediction model was developed to estimate the risk of metastasis using these predictors.

Results: A total of 175 patients were included in this study. A tumor with an endoscopic shape of flat type (0-II type as Paris classification was defined) was significantly related to lower risk of lymphatic metastasis with the frequency of 15.5% (OR: 3.049, 95% CI: 1.363-6.819, P=0.005). The combination of endoscopic morphology with other pathologic characteristics including lymphovascular invasion, length of tumor, depth of tumor invasion into submucosa, and tumor differentiation improved the predictive value of the nodal metastasis. The risk stratification model was developed with a C-index of 0.726 (95% CI: 0.702-0.751), which identified a low risk subgroup with a lymph node rate of 7.2%.

Conclusions: Our results suggest that when a tumor is in flat shape (0-II type) it is related to a less lymphatic metastasis, and the combination of the endoscopic morphology with the other four pathologic variables can yield a more robust approach to predict the risk of lymphatic metastasis in submucosal ESCC.
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http://dx.doi.org/10.21037/jtd.2018.11.77DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344677PMC
December 2018

Comparative analysis of co-occurring mutations of specific tumor suppressor genes in lung adenocarcinoma between Asian and Caucasian populations.

J Cancer Res Clin Oncol 2019 Mar 23;145(3):747-757. Epub 2019 Jan 23.

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.

Introduction: Mutated tumor suppressor genes (TSG) such as TP53, STK11, and MGA are widely-reported. We hypothesized the presence of single mutation or co-occurring mutations in these specific genes may represent a significant therapeutic target for lung adenocarcinoma.

Methods: We sequenced lung adenocarcinoma samples from 677 East-Asian patients, combined them with those from cBioPortal public database (including TCGA) and performed a comparative analysis between Asian and Caucasian populations.

Results: East-Asian lung adenocarcinomas presented distinct driver-mutational distribution compared to that of Caucasians (79% vs 56%, p < 0.001). Similar results were observed in TSG mutations of TP53 (35% vs 46%, p = 0.150), STK11 (4% vs 17%, p = 0.006) and MGA (10% vs 4%, p = 0.166). Compared with none-mutational cases, the patients harboring TSG mutations are more likely to be male (p = 0.009), smokers (p < 0.001), and more advanced disease (p = 0.004). In addition, the TSG-mutated tumors had poorer differentiation (p < 0.001), and more likely to be solid or micropapillary-predominant adenocarcinomas (p < 0.001). Survival analysis showed that both overall survival (OS, p < 0.001) and post-recurrence survival (PRS, p < 0.001) became worse with the accumulation of TSG mutations. However, the prognostic variety was not found in Caucasian patients. Moreover, multivariate analysis proved the accumulation of TSG mutations independently predicts both unfavorable OS (HR = 0.435, 95% CI 0.245-0.774, p = 0.005) and PRS (HR = 0.491, 95% CI 0.269-0.894, p = 0.020) in East-Asian patients, adjusting all other survival-associated factors.

Conclusions: Co-occurring mutations of specific TSGs define unfavorable subgroups of lung adenocarcinoma, implying that the tumor promotion mechanisms contribute to the heterogeneity in tumor evolution. However, the Caucasian population did not show the same results, providing insights into the molecular basis underlying the striking racial disparities of this disease and evidence for different gene-panel designs for different population in the purpose of targeted therapy.
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http://dx.doi.org/10.1007/s00432-018-02828-5DOI Listing
March 2019

Lung Adenocarcinomas Manifesting as Radiological Part-Solid Nodules Define a Special Clinical Subtype.

J Thorac Oncol 2019 04 17;14(4):617-627. Epub 2019 Jan 17.

Department of Thoracic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; School of Life Sciences, Fudan University, Shanghai, People's Republic of China; Institutes of Biomedical Sciences, Fudan University, Shanghai, China. Electronic address:

Introduction: The clinicopathologic features and prognostic predictors of radiological part-solid lung adenocarcinomas were unclear.

Methods: We retrospectively compared the clinicopathologic features and survival times of part-solid tumors with those of pure ground glass nodules (pGGNs) and pure solid tumors treated with surgery at Fudan University Shanghai Cancer Center and evaluated the prognostic implications of consolidation-to-tumor ratio (CTR), solid component size, and tumor size for part-solid lung adenocarcinomas.

Results: A total of 911 patients and 988 pulmonary nodules (including 329 part-solid nodules [PSNs], 501 pGGNs, and 158 pure solid nodules) were analyzed. More female patients (p = 0.015) and nonsmokers (p = 0.003) were seen with PSNs than with pure solid nodules. The prevalence of lymphatic metastasis was lower in patients with PSNs than in those with pure solid tumors (2.2% versus 27% [p < 0.001]). The 5-year lung cancer-specific (LCS) recurrence-free survival and LCS overall survival of patients with PSNs were worse than those of patients with pGGNs (p < 0.001 and p = .042, respectively) but better than those of patients with pure solid tumors ([p < 0.001 and p < 0.0001, respectively]). CTR (OR = 12.90; 95% confidence interval [CI]: 1.85-90.04), solid component size (OR = 1.45; 95% CI: 1.28-1.64), and tumor size (OR = 1.23; 95% CI: 1.15-1.31) could predict pathologic invasive adenocarcinoma for patients with PSNs. None of them could predict the prognosis. Patients receiving sublobar resection had prognoses comparable to those of patients receiving lobectomy (p = .178 for 5-year LCS recurrence-free survival and p = .319 for 5-year LCS overall survival). The prognostic differences between patients with systemic lymph node dissection and those without systemic lymph node dissection were statistically insignificant.

Conclusions: Part-solid lung adenocarcinoma showed clinicopathologic features different from those of pure solid tumor. CTR, solid component size, and tumor size could not predict the prognosis. Part-solid lung adenocarcinomas define one special clinical subtype.
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http://dx.doi.org/10.1016/j.jtho.2018.12.030DOI Listing
April 2019

The lymph node status and histologic subtypes influenced the effect of postoperative radiotherapy on patients with N2 positive IIIA non-small cell lung cancer.

J Surg Oncol 2019 Mar 9;119(3):379-387. Epub 2018 Dec 9.

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Background And Objective: To investigate the role of postoperative radiotherapy (PORT) in IIIA-N2 non-small cell lung cancer (NSCLC) patients and subgroups which derived benefit from PORT.

Methods: A total of 576 patients with pathological IIIA-N2 NSCLC, who underwent complete resection, were identified. Propensity score matching (PSM) methods were used to balance the patients' characteristics between two groups. Overall survival (OS) and relapse-free survival (RFS) were compared between PORT and non-PORT patients.

Results: On multivariable analysis, improved OS remained correlated with younger age, single N2 station involvement, less positive lymph nodes, and chemotherapy. After PSM, 121 PROT patients and 242 non-PORT patients were matched. PORT was not associated improved patients' OS (P = 0.735) or RFS ( P = 0.483). For patients who underwent postoperative chemotherapy (POCT), PORT could improve OS in single N2 station involved patients (HR: 0.572, 95%CI: 0.312 to 1.05, P = 0.040). Patients with papillary predominant adenocarcinoma also benefited from PORT with an increase in OS (HR: 0.350, 95%CI: 0.126 to 0.972, P = 0.033).

Conclusions: For patients with completely resected IIIA-N2 NSCLC, mediastinal lymph node metastasis and histologic subtypes could influence the effect of PORT. Single N2 station involvement and papillary predominant subtype were predictors of benefit from PORT.
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http://dx.doi.org/10.1002/jso.25308DOI Listing
March 2019

Preoperative brain MRI for clinical stage IA lung cancer: is routine scanning rational?

J Cancer Res Clin Oncol 2019 Feb 7;145(2):503-509. Epub 2018 Dec 7.

Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.

Purpose: Early detection and control of lung cancer brain metastases (BMs) are important. However, several guideline recommendations are inconsistent with regard to routine preoperative brain MRI, especially in patients with clinical stage IA lung cancer. Our study evaluated the value of preoperative brain MRI in patients with clinical stage IA lung cancer.

Methods: A retrospective analysis of patients with lung cancer was performed using a prospectively collected database. Clinical data and the results of brain MRI were collected and analyzed.

Results: Patients with pathologically proved primary lung cancer who underwent an MRI at initial diagnosis were identified (3392 patients). In total, 170 patients (5.0%) were diagnosed with BMs. The increased frequency of BMs was significantly associated with advanced clinical stage (P = 0.000) and pathological type (P = 0.011). BMs were detected in 11 out of 1595 patients with clinical stage IA lung cancer (0.7%). BMs were more common in patients with clinical stage cT1c lung cancer (1.9%) than those with clinical stage cT1a or cT1b (0.1%, odds ratio = 21.30, 95% confidence interval: 2.7-166.9, P = 0.000). All patients with stage IA lung cancer and BMs had solid lung lesions (P = 0.002).

Conclusions: Preoperative brain MRI might help identify BMs in patients with lung cancer that has progressed beyond stage IA. In patients with clinical stage IA lung cancer, we do not recommend preoperative brain MRI, but it may potentially be beneficial in those with solid T1c cancers.
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http://dx.doi.org/10.1007/s00432-018-2814-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373267PMC
February 2019

Predictors of Pathologic Tumor Invasion and Prognosis for Ground Glass Opacity Featured Lung Adenocarcinoma.

Ann Thorac Surg 2018 12 8;106(6):1682-1690. Epub 2018 Aug 8.

Department of Thoracic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address:

Background: We make surgical strategies for ground glass opacity (GGO) nodules currently based on thin-section (TS) computed tomography (CT) findings. Whether radiologic measurements could precisely predict tumor invasion and prognosis of GGO-featured lung adenocarcinoma is uncertain.

Methods: We retrospectively evaluated medical records of patients with radiologic GGO nodules undergoing a surgical procedure at Fudan University Shanghai Cancer Center. The study endpoints were the predictive value and prognostic significance of radiologic measurements (consolidation-to-tumor ratio value, consolidation size, and tumor size) for pathologic lung adenocarcinoma.

Results: In this study 736 patients and 841 GGO nodules were included. Five-year lung cancer-specific regression-free survival (LCS-RFS) rate was 95.76% (95% confidence interval [CI], 93.01% to 97.44%). The 5-year LCS overall survival (OS) rate was 98.99% (95% CI, 97.69% to 99.57%). Multivariable analysis showed that tumor invasion (invasive adenocarcinoma [IAD] vs adenocarcinoma in situ [AIS]/minimally invasive adenocarcinoma [MIA], p = 0.020) was the only independent predictor for 5-year LCS-RFS. IAD (hazard ratio, 15.98; 95% CI, 1.55 to 164.35) was correlated with a higher risk of recurrence. Kaplan-Meier analysis showed that only tumor invasion status (IAD vs AIS/MIA, p = 0.003) could predict 5-year lung cancer-specific overall survival (LCS-OS), and IAD had a worse LCS-OS than AIS and MIA. A part-solid component (odds ratio [OR], 9.09; 95% CI, 2.71 to 30.47; p = 0.000), large consolidation size (OR, 3.11; 95% CI, 1.03 to 9.40; p = 0.045), and large tumor size (OR, 5.48; 95% CI, 2.68 to 11.19; p = 0.000) were associated with pathologic IAD. For IAD ≤ 20 mm, segmentectomy and lobectomy had better 5-year LCS-RFS than wedge resection, although the difference was statistically insignificant (p = 0.367). The three types of surgeries provided the similar 5-year LCS-OS (p = 0.834).

Conclusions: Radiologic measurements could not precisely predict tumor invasion and prognosis. Making treatment strategies solely according to TS-CT findings for GGO tumor is inappropriate.
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http://dx.doi.org/10.1016/j.athoracsur.2018.06.058DOI Listing
December 2018

Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial.

J Clin Oncol 2018 09 8;36(27):2796-2803. Epub 2018 Aug 8.

Hong Yang, Hui Liu, Xu Zhang, Qun Li, Ting Lin, Mengzhong Liu, and Jianhua Fu, Sun Yat-sen University Cancer Center, Guangzhou; Yuping Chen, Zhijian Chen, and Geng Wang, Cancer Hospital of Shantou University Medical College, Shantou; Zhijian Chen, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province; Chengchu Zhu, Haihua Yang, Baofu Chen, and Min Kong, Taizhou Hospital, Wenzhou Medical University, Linhai; Weimin Mao and Xiao Zheng, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province; Wentao Fang, Jiaming Wang, Teng Mao, and Xufeng Guo, Shanghai Chest Hospital, Shanghai Jiaotong University; Jiaqing Xiang and Huanjun Yang, Fudan University Shanghai Cancer Center, Shanghai; Zhentao Yu and Qingsong Pang, Tianjin Medical University Cancer Hospital, Tianjin; Yongtao Han and Tao Li, Sichuan Cancer Hospital, Chengdu, Sichuan Province, China; Florian Lordick, University Cancer Center Leipzig, University Medicine Leipzig, Leipzig; Mahmoud Ismail, Academic Hospital of the Charité - Universitätsmedizin, Humboldt University Berlin, Berlin, Germany; Xavier Benoit D'Journo, Aix-Marseille University, Hôpital Nord, Chemin des Bourrely, Marseille Cedex, France; Robert J. Cerfolio, New York University Langone Health; Robert J. Korst, Icahn School of Medicine, Mount Sinai Health System, New York, NY; Robert J. Korst, Valley/Mount Sinai Comprehensive Cancer Care, Paramus, NJ; Nuria M. Novoa, University Hospital of Salamanca, Paseo de San Vicente, Salamanca, Spain; Scott J. Swanson, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Alessandro Brunelli, St James's University Hospital, Leeds, United Kingdom; and Hiran C. Fernando, Inova Fairfax Medical Center, Inova Schar Cancer Institute, Falls Church, VA.

Purpose The efficacy of neoadjuvant chemoradiotherapy (NCRT) plus surgery for locally advanced esophageal squamous cell carcinoma (ESCC) remains controversial. In this trial, we compared the survival and safety of NCRT plus surgery with surgery alone in patients with locally advanced ESCC. Patients and Methods From June 2007 to December 2014, 451 patients with potentially resectable thoracic ESCC, clinically staged as T1-4N1M0/T4N0M0, were randomly allocated to NCRT plus surgery (group CRT; n = 224) and surgery alone (group S; n = 227). In group CRT, patients received vinorelbine 25 mg/m intravenously (IV) on days 1 and 8 and cisplatin 75 mg/m IV day 1, or 25 mg/m IV on days 1 to 4 every 3 weeks for two cycles, with a total concurrent radiation dose of 40.0 Gy administered in 20 fractions of 2.0 Gy on 5 days per week. In both groups, patients underwent McKeown or Ivor Lewis esophagectomy. The primary end point was overall survival. Results The pathologic complete response rate was 43.2% in group CRT. Compared with group S, group CRT had a higher R0 resection rate (98.4% v 91.2%; P = .002), a better median overall survival (100.1 months v 66.5 months; hazard ratio, 0.71; 95% CI, 0.53 to 0.96; P = .025), and a prolonged disease-free survival (100.1 months v 41.7 months; hazard ratio, 0.58; 95% CI, 0.43 to 0.78; P < .001). Leukopenia (48.9%) and neutropenia (45.7%) were the most common grade 3 or 4 adverse events during chemoradiotherapy. Incidences of postoperative complications were similar between groups, with the exception of arrhythmia (group CRT: 13% v group S: 4.0%; P = .001). Peritreatment mortality was 2.2% in group CRT versus 0.4% in group S ( P = .212). Conclusion This trial shows that NCRT plus surgery improves survival over surgery alone among patients with locally advanced ESCC, with acceptable and manageable adverse events.
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http://dx.doi.org/10.1200/JCO.2018.79.1483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145832PMC
September 2018