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Mixed large and small cell neuroendocrine carcinoma of the stomach:A case report and review of literature

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World Journal of Clinical Cases 2022年第16期10卷 5502-5509页

作者： Ze-Feng Li hai-zhen lu Ying-Tai Chen Xiao-Feng Bai Tong-Bo Wang He Fei Dong-Bing Zhao Department of Pancreatic and Gastric Surgical Oncology National Cancer Center/National Clinical Research for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Pathology National Cancer Center/National Clinical Research for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND Gastric neuroendocrine carcinoma(GNEC)is a rare histological subtype of gastric cancer,which is categorized into small cell and large cell neuroendocrine *** is characterized by strong invasiveness and poor *** large and small cell neuroendocrine carcinoma(L/SCNEC)is an extremely rare pathological type of gastric cancer,and there have been no reports on this situation until *** SUMMARY Herein,we first present a 57-year-old patient diagnosed with L/SCNEC of the stomach.A 57-year-old Chinese male presented with epigastric *** gastroscopic biopsy was performed,and pathological examination revealed that the cardia was invaded by *** patient underwent laparoscopic-assisted radical proximal subtotal gastrectomy and was diagnosed with L/*** refused adjuvant treatment and was followed up every 3 *** months after the operation,the patient showed no evidence of local recurrence or distant *** We advocate conducting further genomic studies to explore the origin of gastric large cell and small cell neuroendocrine carcinoma and using different chemotherapy schemes according to large or small cell neuroendocrine carcinoma of the stomach for clinical research to clarify the heterogeneity of GNEC and improve the prognosis of patients with GNEC.

关键词： Gastric cancer Neuroendocrine carcinoma Subtypes Tumorigenesis Treatments Case report

Programmed death-ligand 1 expression in the tumour stroma of colorectal liver oligometastases and its association with prognosis after liver resection

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Gastroenterology Report 2021年第5期9卷 443-450,I0002页

作者： Jian-Hong Peng Yi Tai Yi-Xin Zhao Bao-Jia luo Qing-Jian Ou Zhi-Zhong Pan Lin Zhang zhen-hai lu Department of Colorectal Surgery Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine GuangzhouGuangdongP.R.China Department of Clinical Laboratory Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China

Background The clinical value of programmed death-ligand 1(PD-L1)expression in colorectal liver oligometastases(CLOs)remains *** study aimed to detect PD-L1 in the microenvironment of CLOs and determine its association with patient *** We collected 126 liver-resection specimens from CLO patients who underwent curative liver resection between June 1999 and December ***(IHC)was performed to assess PD-L1 expression in paraffinembedded *** survival(OS)and recurrence-free survival(RFS)were analysed using the Kaplan–Meier method and log-rank *** PD-L1 was mainly expressed in the stroma of liver *** with high PD-L1 expression had a higher proportion of clinical-risk scores(CRSs)of 2–4(67.7%vs 40.4%;P=0.004).With a median 58-month follow-up,patients with high PD-L1 expression had a significantly lower 3-year OS rate(65.5%vs 92.7%;P=0.001)and 3-year RFS rate(34.7%vs 83.8%;P<0.001)than patients with low PD-L1 *** Cox analysis demonstrated that high PD-L1 expression(hazard ratio[HR]=3.581;95%confidence interval[CI]2.301–9.972;P=0.015),CRS 2–4(HR=6.960;95%CI 1.135–42.689;P=0.036)and increased preoperative CA19-9(HR=2.843;95%CI 1.229–6.576;P=0.015)were independent risk factors for *** PD-L1 expression(HR=4.815;95%CI 2.139–10.837;P<0.001)and lymph-node metastasis(HR=2.115;95%CI 1.041–4.297;P=0.038)were independent risk factors for *** This study found that PD-L1 was commonly expressed in the tumour stroma of CLOs and high PD-L1 expression was associated with poor prognosis.

关键词： PD-L1 colorectal liver oligometastases expression prognosis

The loss-of-function mutations and down-regulated expression of ASB3 gene promote the growth and metastasis of colorectal cancer cells

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Chinese Journal of Cancer 2017年第1期36卷 11-25页

作者： Wu-Ying Du zhen-hai lu Wen Ye Xiang Fu Yi Zhou Chun-Mei Kuang Jiang-Xue Wu Zhi-Zhong Pan Shuai Chen Ran-Yi Liu Wen-Lin Huang State Key Laboratory of Oncology in South China Collaborative Innovation Center of Cancer Medicine Sun Yat-sen University Cancer Center Department of Radiation Oncology University of Arkansas for Medical Sciences Department of Oncology The First Affiliated Hospital Sun Yat-sen University Department of Radio-chemotherapy Shangrao People’s Hospital Guangdong Provincial Key Laboratory of Tumor-targeted Drug and Guangzhou Enterprise Key Laboratory of Gene Medicine Guangzhou Doublle Bioproducts Co. Ltd.

Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses. However, its effects on oncogenesis are unclear. This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer(CRC).Methods: We used next?generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines, and used real?time quantitative polymerase chain reaction, Western blotting, and immunohistochemical or immunofluorescence assay to determine gene expression. We evaluated cell proliferation by MTT and colony for?mation assays, tested cell cycle distribution by flow cytometry, and assessed cell migration and invasion by transwell and wound healing assays. We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor ***: We found that ASB3 gene was frequently mutated(5.3%) and down?regulated(70.4%) in CRC cases. Knock?down of endogenous ASB3 expression promoted CRC cell proliferation, migration, and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo. Conversely, the ectopic overexpression of wild?type ASB3, but not that of ASB3 mutants that occurred in clinical CRC tissues, inhibited tumor growth and metastasis. Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial?mesenchymal transition, which was characterized by the up?regulation of β?catenin and E?cadherin and the down?regulation of transcription factor 8, N?cadherin, and ***: ASB3 dysfunction resulted from gene mutations or down?regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.

关键词： Ankyrin repeat and SOCS box protein 3(ASB3) Colorectal cancer Epithelial-mesenchymal transition Cell proliferation Tumor metastasis

Oxaliplatin-containing adjuvant chemotherapy improves the survival of locally advanced rectal cancer patients with pathological complete response after pre-operative chemoradiotherapy

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Gastroenterology Report 2018年第3期6卷 195-201,I0002页

作者： Jian-Hong Peng Jun-Zhong Lin Yu-Ming Rong Ying Zhu Yu-Xiang Deng Yu-Jie Zhao zhen-hai lu Xiao-Jun Wu Zhi-Zhong Pan Department of Colorectal Surgery Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine651 Dongfeng Road EastGuangzhouGuangdong 510060P.R.China VIP Region Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine651 Dongfeng Road EastGuangzhouGuangdong 510060P.R.China

Background:The necessity for adjuvant chemotherapy(ACT)in locally advanced rectal cancer(LARC)patients who achieve pathological complete response(pCR)after pre-operative chemoradiotherapy(CRT)is still not *** aimed to investigate the therapeutic value of ACT in these ***:Clinical data were retrospectively collected from 105 consecutive LARC patients who achieved pCR after pre-operative CRT and underwent radical tumor resection between December 2008 and April 2014 in a comprehensive cancer *** chemotherapy(CT)was administered by combining oxaliplatin with capecitabine(XELOX regimen).Disease-free survival(DFS)and overall survival(OS)rates of patients with or without ACT were ***:Eighty-three(79.0%)patients received ACT and 22(21.0%)did *** a median follow-up of 49 months,the ACT group had a significantly higher 3-year DFS rate(92.8 vs 86.4%,p=0.029)and 3-year OS rate(95.1 vs 86.1%,p=0.026)than the non-ACT *** multivariable analyses,the presence of ACT was an independent prognostic factor for DFS(hazard ratio[HR]:0.271;95%confidence interval(CI):0.080–0.916;p=0.036)but not for *** benefit was more obvious in patients younger than 60 years via subgroup analysis(adjusted HR:0.106;95%CI:0.019–0.606;p=0.012).Conclusions:Oxaliplatin-containing ACT may confer survival benefits to patients with pCR,particularly younger ***,the routine use of ACT in patients with pCR needs further validation.

关键词： Adjuvant chemotherapy rectal cancer pre-operative chemoradiotherapy pathological complete response survival

New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma:a retrospective study

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Chinese Journal of Cancer 2016年第12期35卷 713-724页

作者： Qing-Qing Cai Li-Yang Hu Qi-Rong Geng Jie Chen zhen-hai lu Hui-Lan Rao Qing Liu Wen-Qi Jiang Hui-Qiang Huang Tong-Yu Lin Zhong-Jun Xia State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuang-zhou 510060GuangdongP.R.China. Department of Medical Oncology Sun Yat-sen University Cancer Center651 Dongfeng Road EastGuang-zhou 510060GuangdongP.R.China. Department of Hematology Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China. Guangdong Province Key Laboratory of Arrhythmia and Elec-trophysiology Guangzhou 510120GuangdongP.R.China. Department of Radiotherapy Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityGuangzhou 510120GuangdongP.R.China. Department of Colorectal Carci-noma Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China. Department of Pathology Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China. Department of Cancer Preven-tion Research Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China.

Background: In patients with difuse large B?cell lymphoma(DLBCL), central nervous system(CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the eicacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse ***: A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat?sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R?CHOP regimen(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen(cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathe?cal chemotherapy prophylaxis(methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R?CHOP set in particular, the Kaplan–Meier method coupled with the log?rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Diferences were evaluated using a two?tailed test, and P 110 U/L(HR = 3.59, 95% CI 1.25–10.34), serum albumin(ALB) <35 g/L(HR = 3.63, 95% CI 1.25–10.51), treatment with rituxi?mab(HR = 0.34, 95% CI 0.12–0.96), and a time to complete remission ≤ 108 days(HR = 0.22, 95% CI 0.06–0.78) were independent p

关键词： Diffuse large B?cell lymphoma Central nervous system relapse Risk factor Rituximab Intrathecal chemotherapy prophylaxis

Surgery with versus without preoperative concurrent chemoradiotherapy for mid/low rectal cancer: an interim analysis of a prospective, randomized trial

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Chinese Journal of Cancer 2015年第9期34卷 26-35页

作者： Wen-Hua Fan Fu-Long Wang zhen-hai lu Zhi-Zhong Pan Li-Ren Li Yuan-Hong Gao Gong Chen Xiao-Jun Wu Pei-Rong Ding Zhi-Fan Zeng De-Sen Wan State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat-sen University Cancer Center Department of Colorectal Surgery Sun Yat-sen University Cancer Center Department of Radiation Oncology Sun Yat-sen University Cancer Center

Introduction: Multimodality therapy, including preoperative chemoradiotherapy(CRT) and total mesorectal excision(TME), has effectively reduced local recurrence rates of rectal cancer over the past decade. However, the benefits and risks of the addition of neoadjuvant CRT to surgery need to be evaluated. This study was to compare the efficacy of TME with versus without preoperative concurrent chemoradiotherapy(CCRT) involving XELOX regimen(oxaliplatin plus capecitabine) in Chinese patients with stages II and III mid/low rectal ***: We randomly assigned patients to the TME group(TME without preoperative CCRT) or CCRT + TME group(TME with preoperative CCRT). The primary endpoint was disease-free survival(DFS); the secondary endpoints were overall survival(OS), local and distant recurrence, tumor response to CRT, toxicity, sphincter preservation, and surgical complications. An interim analysis of the potential inferiority of DFS in the CCRT + TME group was planned when the first 180 patients had been followed up for at least 6 ***: A total of 94 patients in the TME group and 90 patients in the CCRT + TME group were able to be evaluated. The 3-year DFS and OS rates were 86.3 % and 91.5 % in the whole cohort, respectively. The 3-year DFS rates of the TME and CCRT + TME groups were 85.7% and 87.9 %(P = 0.766), respectively, and the 3-year OS rates were 90.7 % and 92.3 %(P = 0.855), respectively. The functional sphincter preservation rates of the TME and CCRT +TME groups were 71.3 % and 70.0 %(P = 0.849), respectively. In the TME group, 16(17.0 %) patients were proven to have p TNM stage I disease after surgery. In the CCRT + TME group, 32(35.6 %) patients achieved a pathologic complete response(p CR).Conclusions: Preliminary results indicated no significant differences in the DFS, OS, or functional sphincter preservation rates between the TME and CCRT + TME groups. However, preoperative CCRT with XELOX yielded a high p CR rate. Newer technique

关键词： Rectal cancer, Total mesorectal excision, Chemoradiotherapy, Oxaliplatin, Capecitabine

Identification of biomarkers for hepatocellular carcinoma by semiquantitative immunocytochemistry

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World Journal of Gastroenterology 2014年第19期20卷 5826-5838页

作者： Hong Mu Kai-Xuan Lin Hong Zhao Shu Xing Cong Li Fang Liu hai-zhen lu Ze Zhang Yu-Lin Sun Xi-Yun Yan Jian-Qiang Cai Xiao-Hang Zhao State Key Laboratory of Molecular Oncology Cancer Institute HospitalChinese Academy of Medical Sciences and Peking Union Medical College Center of Basic Medical Sciences Navy General Hospital of Chinese PLA Department of Abdominal Surgery Cancer Institute HospitalChinese Academy of Medical Science and Peking Union Medical College Key Laboratory of Protein and Peptide Pharmaceutical National Laboratory of BiomacromoleculesInstitute of BiophysicsChinese Academy of Sciences Department of Pathology Cancer Institute HospitalChinese Academy of Medical Sciences and Peking Union Medical College

AIM: To investigate the expression of key biomarkers in hepatoma cell lines, tumor cells from patients’ blood samples, and tumor tissues.

关键词： Hepatocellular carcinoma Biomarker Immunocytochemistry Semiquantitative analysis Three-dimensional reconstruction

Neoadjuvant oxaliplatin and capecitabine combined with bevacizumab plus radiotherapy for locally advanced rectal cancer: results of a single-institute phase II study

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Cancer Communications 2018年第1期38卷 263-271页

作者： Xin Yu Qiao-xuan Wang Wei-wei Xiao Hui Chang Zhi-fan Zeng zhen-hai lu Xiao-jun Wu Gong Chen Zhi-zhong Pan De-sen Wan Pei-rong Ding Yuan-hong Gao Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuang-zhouP.R.China Department of Radiation Oncology Sun Yat-sen University Cancer Center651 Dongfeng Rd EastGuangzhou 510060P.R.China Department of Colorectal Surgery Sun Yat-sen University Cancer Center651 Dongfeng Rd EastGuangzhou 510060P.R.China

Background:Neoadjuvant chemoradiotherapy followed by surgery is recommended as the standard of care for locally advanced rectal cancer,reducing local recurrence but not distant *** systemic therapy is warranted to reduce the risk of distant *** present study aimed to evaluate the safety and efficacy of neo-adjuvant oxaliplatin and capecitabine(XELOX)combined with bevacizumab plus radiotherapy for locally advanced rectal ***:Patients with stages II to III rectal cancer received one cycle of induction chemotherapy and concurrent chemoradiotherapy with XELOX plus *** was performed 6-8 weeks after completion of radiotherapy,and postoperative chemotherapy with three cycles of XELOX and two cycles of capecitabine were *** primary endpoints were pathologic complete response(pCR)rate and safety,and the secondary endpoints were 3-year overall survival and progression-free ***:Forty-five patients were enrolled between February 2013 and April *** completed the neoadjuvant *** patients(15.6%)refused subsequent surgical therapy for personal reasons,and the other 38 patients received radical resection,with a sphincter preservation rate of 84.2%and a pCR rate of 39.5%.Toxicity was acceptable,with grades 3-4 hematological toxicity and diarrhea observed in six and two patients,*** of anastomotic leak that required surgical intervention was 13.3%.After a median follow-up period of 37 months,five patients developed disease progression and two died of *** 3-year overall survival rate and 3-year progres-sion-free survival rate were 95.3%and 88.6%,***:The addition of bevacizumab to neoadjuvant chemoradiotherapy resulted in a satisfying pCR rate and 3-year survival,but also may increase the risk of anastomotic leak,thus this regimen is not suitable to be considered for regular recommendation for locally advanced rectal cancer.

关键词： Bevacizumab Neoadjuvant chemoradiotherapy Locally advanced rectal cancer Safety Efficacy

Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer

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Chinese Journal of Cancer 2016年第10期35卷 535-545页

作者： Bo Qiu Pei-Rong Ding Ling Cai Wei-Wei Xiao Zhi-Fan Zeng Gong Chen zhen-hai lu Li-Ren Li Xiao-Jun Wu Rene-Olivier Mirimanoff Zhi-Zhong Pan Rui-Hua Xu Yuan-Hong Gao State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat?sen University Cancer Center Department of Radiation Oncology Sun Yat?sen University Cancer Center Department of Colorectal Surgery Sun Yat?sen University Cancer Center Department of Radiation Oncology Centre Hospitalier Universitaire Vaudois Department of Medical Oncology Sun Yat?sen University Cancer Center

Background: Complete resection of locally advanced sigmoid colon cancer(LASCC) is sometimes difficult. Patients with LASCC have a dismal prognosis and poor quality of life, which has encouraged the evaluation of alternative multimodality treatments. This prospective study aimed to assess the feasibility and efficacy of neoadjuvant chemora?diotherapy(neo CRT) followed by surgery as treatment of selected patients with unresectable ***: We studied the patients with unresectable LASCC who received neo CRT followed by surgery between October 2010 and December 2012. The neoadjuvant regimen consisted of external?beam radiotherapy to 50 Gy and capecitabine?based chemotherapy every 3 weeks. Surgery was scheduled 6–8 weeks after ***: Twenty?one patients were included in this study. The median follow?up was 42 months(range, 17–57 months). All patients completed neo CRT and surgery. Resection with microscopically negative margins(R0 resection) was achieved in 20 patients(95.2%). Pathologic complete response was observed in 8 patients(38.1%). Multivisceral resection was necessary in only 7 patients(33.3%). Two patients(9.5%) experienced grade 2 postopera?tive complications. No patients died within 30 days after surgery. For 18 patients with pathologic M0(yp M0) disease, the cumulative probability of 3?year local recurrence?free survival, disease?free survival and overall survival was 100.0%, 88.9% and 100.0%, respectively. For all 21 patients, the cumulative probability of 3?year overall survival was 95.2% and bladder function was well ***: For patients with unresectable LASCC, preoperative chemoradiotherapy and surgery can be performed safely and may result in an increased survival rate.

关键词：手术切除结肠癌患者化疗晚期前放 CRT 生存率