1.Rethinking of neoadjuvant therapy for patients with initially resectable colorectal cancer liver metastases
Gong CHEN ; Yuhong LI ; Rongxin ZHANG ; Binkui LI ; Fulong WANG ; Yunfei YUAN ; Zhizhong PAN ; Desen WAN
Chinese Journal of Hepatobiliary Surgery 2020;26(7):488-492
Surgical resection is the best method for patients with colorectal cancer liver metastases. However, tumor recurrence rate is still high after surgery. Preoperative chemotherapy can help shrink the tumor, test biological behavior, and reduce recurrence rate; but it may also cause liver injury and delay surgery. There is still controversy whether neoadjuvant chemotherapy should be performed and how to select patients from chemotherapy before surgery. Thus, in this article, combined the research progress and the clinical experience of author's center, we discuss this issue in 4 aspects: the development of neoadjuvant chemotherapy; the indications and guideline recommendation for neoadjuvant chemotherapy; the selection of neoadjuvant chemotherapy regimens; common problems in neoadjuvant chemotherapy.
2.Surgical treatment and prognostic analysis for 57 patients with gastrointestinal lymphoma.
Jianhong PENG ; Binyi XIAO ; Yixin ZHAO ; Cong LI ; Rongxin ZHANG ; Gong CHEN ; Liren LI ; Zhenhai LU ; Peirong DING ; Desen WAN ; Zhizhong PAN ; Xiaojun WU ;
Chinese Journal of Gastrointestinal Surgery 2017;20(9):1040-1044
OBJECTIVETo explore clinicopathologic characteristics, surgical features and prognostic factors in patients with primary gastrointestinal lymphoma(PGIL) in order to provide evidence for optimizing surgical treatment.
METHODSClinicopathological data of 57 PGIL patients undergoing abdominal surgery in Sun Yat-sen University Cancer Center between October 1990 and January 2015 were retrospectively collected. The survival rates were compared among patients with different clinicopathologic characteristics by Kaplan-Meier method, while Cox regression model was employed to analyze the prognostic factors.
RESULTSAmong 57 patients, 43 were male and 14 were female, with a median age of 48 (range 16 to 80) years. Seventeen (29.8%) cases were classified as Musshoff I( stage, 19 (33.3%) cases as II( stage, 9 (15.8%) cases as III( stage, and 12(21.1%) cases as IIII( stage. Forty-four (77.2%) cases underwent selective operation, 13(22.8%) cases underwent emergent operation due to acute abdomen. Thirty-two(56.1%) cases had radical resection, 18 (31.6%) cases had partial resection and the rest 7(12.3%) cases failed to perform resection. Four (7.0%) cases received simple surgical operation, and 53 (93.0%) cases received comprehensive treatment, including 5(8.8%) cases with preoperative chemotherapy and surgery, 40 (70.2%) cases with surgery and postoperative chemotherapy, and 8 (14.0%) cases with surgery and perioperative chemotherapy. Stage III( and IIII( accounted for 76.9%(10/13) in patients undergoing emergent operation and accounted for 25.0%(11/44) in patients undergoing selective operation, whose difference was statistically significant (χ=9.503, P=0.002). Univariate prognostic analysis showed that T lymphocyte source pathological cell phenotype (P=0.000), clinical Musshoff stage III( and IIII((P=0.001), emergent operation (P=0.000) and incomplete tumor resection(P=0.007) had worse 5-year overall survival. Multivariate Cox regression analysis indicated that tumor pathological cell phenotype (HR=13.75, 95%CI:3.546-53.308, P=0.000) and surgical timing (HR=7.497, 95%CI:1.163-48.313, P=0.034) were independent prognostic risk factors of patients with stage I( and II(.
CONCLUSIONSSurgical operation is an important part of comprehensive treatment for PGIL. T lymphocyte source and ulcerative lymphoma indicates poorer prognosis.
3.Mid-term outcomes of a prospective phase Ⅱ trial of preoperative sandwich-like neoadjuvant chemoradiotherapy for locally advanced rectal cancer
Jiawang WEI ; Rong ZHANG ; Weiwei XIAO ; Xin YU ; Suping GUO ; Zhifan ZENG ; Gong CHEN ; Zhizhong PAN ; Desen WAN ; Peirong DING ; Yuanhong GAO
Chinese Journal of Radiation Oncology 2017;26(7):759-762
Objective To evaluate the mid-to long-term survival benefits of preoperative sandwich-like neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC).Methods A total of 45 LARC patients who underwent neoadjuvant sandwich CRT in the form of XELOX regimen prior to,concurrently with,and following volumetric modulated arc radiotherapy (VMAT) in 2012 were enrolled in this study.VMAT was given at a gross tumor volume dose of 50 Gy in 25 fractions,and a clinical target volume dose of 45-46 Gy in 25 fractions.Total mesorectal excision was performed 6 to 8 weeks after completion of VMAT.The overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method,and survival comparison and univariate prognostic analysis were performed using the log-rank test.Results The median follow-up time was 46.7 months.There was no local recurrence detected among the patients.The 3-year distant metastasis (DM) rate was 18%,and the 3-year OS and DFS were 96% and 84%,respectively.Univariate analysis indicated that perineural invasion,N1-N2 pathology (pathological stage Ⅲ),and Ca-199>35 U/ml before treatment were risk factors for DM (P=0.000,0.000,and 0.013,respectively).Conclusions The significant short-term efficacy of preoperative sandwich-like neoadjuvant CRT can be extended to a positive mid-term survival in LARC patients.However,further phase Ⅲ clinical studies will be needed to confirm this finding.
4.Prognostic value of preoperative prognostic nutritional index and its associations with systemic inflammatory response markers in patients with stage Ⅲ colon cancer
Peng JIANHONG ; Zhang RONGXIN ; Zhao YIXIN ; Wu XIAOJUN ; Chen GONG ; Wan DESEN ; Lu ZHENHAI ; Pan ZHIZHONG
Chinese Journal of Cancer 2017;36(11):635-646
Background: The prognostic nutritional index (PNI) has been widely applied for predicting survival outcomes of patients with various malignant tumors. Although a low PNI predicts poor prognosis in patients with colorectal cancer after tumor resection, the prognostic value remains unknown in patients with stage Ⅲ colon cancer undergoing cura-tive tumor resection followed by adjuvant chemotherapy. This study aimed to investigate the prognostic value of PNI in patients with stageⅢ colon cancer. Methods: Medical records of 274 consecutive patients with stage Ⅲ colon cancer undergoing curative tumor resec-tion followed by adjuvant chemotherapy with oxaliplatin and capecitabine between December 2007 and December 2013 were reviewed. The optimal PNI cutoff value was determined using receiver operating characteristic (ROC) curve analysis. The associations of PNI with systemic inflammatory response markers, including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) level, and clinicopathologic characteristics were assessed using the Chi square or Fisher's exact test. Correlation analysis was performed using Spearman's correlation confficient. Disease-free survival (DFS) and overall survival (OS) stratified by PNI were analyzed using Kaplan–Meier method and log-rank test, and prognostic factors were identified by Cox regression analyses. Results: The preoperative PNI was positively correlated with LMR (r= 0.483,P < 0.001) and negatively correlated with NLR (r=? 0.441,P < 0.001), PLR (r=? 0.607,P < 0.001), and CRP level (r=? 0.333,P < 0.001). A low PNI (≤ 49.22) was significantly associated with short OS and DFS in patients with stage IIIC colon cancer but not in patients with stage IIIA/IIIB colon cancer. In addition, patients with a low PNI achieved a longer OS and DFS after being treated with 6–8 cycles of adjuvant chemotherapy than did those with < 6 cycles. Multivariate analyses revealed that PNI was inde-pendently associated with DFS (hazard ratios 2.001; 95% confidence interval 1.157–3.462;P= 0.013). Conclusion: The present study identified preoperative PNI as a valuable predictor for survival outcomes in patients with stage Ⅲ colon cancer receiving curative tumor resection followed by adjuvant chemotherapy.
5.Expression of voltage-gated sodium channel Nav1.5 in non-metastatic colon cancer and its associations with estrogen receptor(ER)-βexpression and clinical outcomes
Peng JIANHONG ; Ou QINGJIAN ; Wu XIAOJUN ; Zhang RONGXIN ; Zhao QIAN ; Jiang WU ; Lu ZHENHAI ; Wan DESEN ; Pan ZHIZHONG ; Fang YUJING
Chinese Journal of Cancer 2017;36(12):694-703
Background: Voltage-gated sodium channel 1.5 (Nav1.5) potentially promotes the migratory and invasive behaviors of colon cancer cells. Hitherto, the prognostic significance of Nav1.5 expression remains undetermined. The present study aimed to explore the associations of Nav1.5 expression with clinical outcomes and estrogen receptor-β (ER-β) expression in non-metastatic colon cancer patients receiving radical resection. Methods: A total of 269 consecutive patients with pathologically confirmed stages Ⅰ–Ⅲ colon cancer who under-went radical resection were selected. Nav1.5 and ER-β expression was detected by using immunohistochemistry (IHC) on tissue microarray constructed from paraffin-embedded specimens. IHC score was determined according to the percentage and intensity of positively stained cells. Statistical analysis was performed with the X-tile method, k coef-ficient, Chi square test or Fisher's exact test, logistic regression, log-rank test, and Cox proportional hazards models. Results: We found that Nav1.5 was commonly expressed in tumor tissues with higher mean IHC score as compared with matched tumor-adjacent normal tissues (5.1 ± 3.5 vs. 3.5 ± 2.7, P < 0.001). The high expression of Nav1.5 in colon cancer tissues was associated with high preoperative carcinoembryonic antigen level [odds ratio (OR) = 2.980;95% confidential interval (CI) 1.163–7.632; P = 0.023] and high ER-β expression (OR = 2.808; 95% CI 1.243–6.343;P = 0.013). Log-rank test results showed that high Nav1.5 expression contributed to a low 5-year disease-free survival (DFS) rate in colon cancer patients (77.2% vs. 92.1%, P = 0.048), especially in patients with high ER-β expression tumor (76.2% vs. 91.3%, P = 0.032). Analysis with Cox proportional hazards model demonstrated that high Nav1.5 expression [hazard ratio (HR) = 2.738; 95% CI 1.100–6.819; P = 0.030] and lymph node metastasis (HR = 2.633; 95% CI 1.632–4.248; P < 0.001) were prognostic factors for unfavorable DFS in colon cancer patients. Conclusions: High expression of Nav1.5 was associated with high expression of ER-β and indicated unfavorable oncologic prognosis in patients with non-metastatic colon cancer.
6.Clinical study on locally advanced rectal cancer patients with pathological complete response after neoadjuvant chemoradiotherapy.
Gong CHEN ; Rongxin ZHANG ; Xiaojun WU ; Zhenhai LU ; Peirong DING ; Zhizhong PAN ; Desen WAN
Chinese Journal of Gastrointestinal Surgery 2016;19(6):664-667
OBJECTIVETo explore the efficacy prediction of the locally advanced rectal cancer patients, especially those with pathological complete response(pCR), receiving neoadjuvant chemoradiotherapy in order to execute precise preoperative neoadjuvant chemoradiotherapy.
METHODSFrom January 2000 to January 2011, 125 patients diagnosed as locally advanced rectal cancer receiving preoperative neoadjuvant chemoradiotherapy in our department with complete data were enrolled in this study, including 85 males and 40 females with mean age of 54(15 to 77) years old. All the patients received radiotherapy with 46 Gy(23 times) and administered XELOX regimen (oxaliplatin 100 mg/m(2) plus capecitabine 2 000 mg/m(2)) for 2 courses simultaneously, and underwent radical operation 6 to 8 weeks after chemoradiotherapy. The data of these patients were analyzed retrospectively. Pathological remission was divided into 4 grades. Patients achieving grade 4 were defined as pCR, and those achieving above grade 2 were defined as better response. Logistic regression analysis was used to identify significant predictors of pCR.
RESULTSAmong 125 patients, 16(12.8%) achieved pCR status, and 90(72.0%) had better response to the neoadjuvant chemoradiotherapy. Logistic regression analysis showed that age(OR:1.060, P=0.037) and preoperative positive lymph nodes detected by endorectal ultrasonography (OR:0.059, P=0.006) were independent predictors of pCR after neoadjuvant chemoradiotherapy.
CONCLUSIONSPreoperative existence of lymph node metastasis around bowel indicates the poor response to neoadjuvant chemoradiotherapy. Age is associated with pCR in patients receiving neoadjuvant chemoradiotherapy.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Capecitabine ; therapeutic use ; Chemoradiotherapy ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Female ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Rectal Neoplasms ; therapy ; Retrospective Studies ; Treatment Outcome ; Young Adult
7.Clinical study of bevacizumab combined with preoperative chemotherapy for colorectal cancer patients with liver metastases
Zhenhai LU ; Fulong WANG ; Jianhong PENG ; Yunfei YUAN ; Wu JIANG ; Yuhong LI ; Xiaojun WU ; Gong CHEN ; Peirong DING ; Liren LI ; Desen WAN ; Zhizhong PAN
Chinese Journal of Hepatic Surgery(Electronic Edition) 2016;5(3):181-185
ObjectiveTo explore the efficacy and safety of bevacizumab combined with preoperative chemotherapy for colorectal cancer patients with liver metastases.MethodsClinical data of 89 colorectal cancer patients with liver metastases admitted and treated in Sun Yat-sen University Cancer Center between May 2009 and August 2013 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. According to the first-line chemotherapy regimens, the patients were divided into the bevacizumab combined with preoperative chemotherapy group (bevacizumab group,n=32) and the simple preoperative chemotherapy group (the chemotherapy group,n=57). Among the patients in the bevacizumab group, 24 were males and 8 were females with the age ranging from 29 to 74 years old and the median of 59 years old, 22 were with colon cancer and 10 were with rectal cancer. Among the patients in the chemotherapy group, 42 were males and 15 were females with the age ranging from 28 to 74 years old and the median of 57 years old, 42 were with colon cancer and 15 were with rectal cancer. The progression-free survival, response rate, resection rate and conversion rate of liver metastases and adverse effect incidence of preoperative therapy in two groups were observed and compared. The rates were compared using Chi-square test, and the survival analysis was conducted using Kaplan-Meier method and Log-rank test.ResultsThe median progression-free survival was 16 months in the bevacizumab group and 13 months in the chemotherapy group, and no significant difference was observed in the progression-free survival rate between two groups (χ2=0.030,P>0.05). The response rate, resection rate and conversion rate of liver metastases were respectively 59%(19/32), 69%(22/32) and 53%(17/32) in the bevacizumab group and 39%(22/57), 54%(31/57) and 40%(23/57) in the chemotherapy group, and no signiifcant differences were observed (χ2=3.561, 1.755, 0.983;P>0.05). The overall incidence of adverse events was 12%(4/32) in the bevacizumab group with 2 cases of neutropenia, 1 case of hand-foot syndrome and 1 case of gradeⅢ gums bleeding, while the overall incidence of adverse events was 9%(5/57) in the chemotherapy group with 3 cases of thrombocytopenia, 1 case of neutropenia and 1 case of liver function impairment. And no signiifcant difference was observed between two groups (χ2=0.313, P>0.05).ConclusionsBevacizumab combined with preoperative chemotherapy is safe and has potential curative effect to prolong the disease-free survival for colorectal cancer patients with liver metastases.
8.Impact of macroscopic enlarged lymph node on stage II colorectal cancer prognosis and its potential mechanism.
Wenhua FAN ; Ziyi HUANG ; Yujing FANG ; Desen WAN ; Zhizhong PAN ; Liren LI
Chinese Journal of Gastrointestinal Surgery 2015;18(6):558-562
OBJECTIVETo evaluate the impact of macroscopic enlarged lymph node on the clinicopathological characteristics of stage II colorectal cancer, and to explore the potential mechanism.
METHODSClinicopathological data of 116 consecutive patients with stage II colorectal cancer, who underwent colorectal radical resection and were identified as stage II colorectal cancer without mesenteric metastasis by postoperative pathology, in our department between December 2001 and December 2002 were analyzed retrospectively. All the patients were examined by the surgeons with gross appearance to decide the enlarged lymph nodes as metastasis during operation. There were 43 patients with macroscopic enlarged lymph nodes and 73 without such lymph nodes. Survival rate was compared between the two groups. Impact of macroscopic enlarged lymph node on the prognosis of stage II colorectal cancer was analyzed. Structure of macroscopic enlarged lymph node was observed. CK expression in 107 macroscopic enlarged lymph nodes from 43 cases was examined by immunohistochemistry.
RESULTSThe 10-year disease-free survival (DFS) of the whole group was 83.5%. The 10-year DFS of patients with macroscopic enlarged lymph nodes was 75.9%, which was significantly lower than 89.3% (P=0.038) of patients without macroscopic enlarged lymph nodes. Univariate analysis showed that macroscopical enlarged lymph node (P=0.038), perioperative blood transfusion (P=0.004), number of retrieved lymph nodes (P=0.016), concomitant disease (P=0.003), and preoperative serum carcinoembryonic antigen (CEA) level (P=0.050) were related to the prognosis of all the 116 patients. Multivariate analysis showed that macroscopical enlarged lymph node (P=0.044), number of retrieved lymph nodes (P=0.021), and perioperative blood transfusion (P=0.032) were independent prognostic factors. Haematoxylin and eosin (HE) staining indicated that enlarged lymph nodes had hyperplasia reaction. Immunohistochemistry showed that among 107 enlarged lymph nodes, 1 had macrometastases, 1 micrometastasis, 4 isolated tumor cell (ITC), and the rest 101 had no positive CK expression.
CONCLUSIONMacroscopic enlarged lymph node indicates a poor prognosis in patients with stage II colorectal cancer.
Carcinoembryonic Antigen ; Colorectal Neoplasms ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Lymph Nodes ; Lymphatic Metastasis ; Multivariate Analysis ; Neoplasm Micrometastasis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Rate
9.Impact of macroscopic enlarged lymph node on stage colorectal cancer prognosis and its potential mechanism
Wenhua FAN ; Ziyi HUANG ; Yujing FANG ; Desen WAN ; Zhizhong PAN ; Liren LI
Chinese Journal of Gastrointestinal Surgery 2015;(6):558-562
Objective To evaluate the impact of macroscopic enlarged lymph node on the clinicopathological characteristics of stage Ⅱ colorectal cancer, and to explore the potential mechanism. Methods Clinicopathological data of 116 consecutive patients with stage Ⅱ colorectal cancer, who underwent colorectal radical resection and were identified as stage Ⅱ colorectal cancer without mesenteric metastasis by postoperative pathology , in our department between December 2001 and December 2002 were analyzed retrospectively. All the patients were examined by the surgeons with gross appearance to decide the enlarged lymph nodes as metastasis during operation. There were 43 patients with macroscopic enlarged lymph nodes and 73 without such lymph nodes. Survival rate was compared between the two groups. Impact of macroscopic enlarged lymph node on the prognosis of stage Ⅱcolorectal cancer was analyzed. Structure of macroscopic enlarged lymph node was observed. CK expression in 107 macroscopic enlarged lymph nodes from 43 cases was examined by immunohistochemistry. Results The 10-year disease-free survival(DFS) of the whole group was 83.5%. The 10-year DFS of patients with macroscopic enlarged lymph nodes was 75.9% , which was significantly lower than 89.3%(P=0.038) of patients without macroscopic enlarged lymph nodes. Univariate analysis showed that macroscopical enlarged lymph node (P=0.038), perioperative blood transfusion (P=0.004), number of retrieved lymph nodes (P=0.016), concomitant disease (P=0.003), and preoperative serum carcinoembryonic antigen (CEA) level (P=0.050) were related to the prognosis of all the 116 patients. Multivariate analysis showed that macroscopical enlarged lymph node (P=0.044), number of retrieved lymph nodes (P=0.021), and perioperative blood transfusion (P=0.032) were independent prognostic factors. Haematoxylin and eosin (HE) staining indicated that enlarged lymph nodes had hyperplasia reaction. Immunohistochemistry showed that among 107 enlarged lymph nodes, 1 had macrometastases, 1 micrometastasis, 4 isolated tumor cell (ITC), and the rest 101 had no positive CK expression. Conclusion Macroscopic enlarged lymph node indicates a poor prognosis in patients with stage Ⅱ colorectal cancer.
10.Impact of macroscopic enlarged lymph node on stage colorectal cancer prognosis and its potential mechanism
Wenhua FAN ; Ziyi HUANG ; Yujing FANG ; Desen WAN ; Zhizhong PAN ; Liren LI
Chinese Journal of Gastrointestinal Surgery 2015;(6):558-562
Objective To evaluate the impact of macroscopic enlarged lymph node on the clinicopathological characteristics of stage Ⅱ colorectal cancer, and to explore the potential mechanism. Methods Clinicopathological data of 116 consecutive patients with stage Ⅱ colorectal cancer, who underwent colorectal radical resection and were identified as stage Ⅱ colorectal cancer without mesenteric metastasis by postoperative pathology , in our department between December 2001 and December 2002 were analyzed retrospectively. All the patients were examined by the surgeons with gross appearance to decide the enlarged lymph nodes as metastasis during operation. There were 43 patients with macroscopic enlarged lymph nodes and 73 without such lymph nodes. Survival rate was compared between the two groups. Impact of macroscopic enlarged lymph node on the prognosis of stage Ⅱcolorectal cancer was analyzed. Structure of macroscopic enlarged lymph node was observed. CK expression in 107 macroscopic enlarged lymph nodes from 43 cases was examined by immunohistochemistry. Results The 10-year disease-free survival(DFS) of the whole group was 83.5%. The 10-year DFS of patients with macroscopic enlarged lymph nodes was 75.9% , which was significantly lower than 89.3%(P=0.038) of patients without macroscopic enlarged lymph nodes. Univariate analysis showed that macroscopical enlarged lymph node (P=0.038), perioperative blood transfusion (P=0.004), number of retrieved lymph nodes (P=0.016), concomitant disease (P=0.003), and preoperative serum carcinoembryonic antigen (CEA) level (P=0.050) were related to the prognosis of all the 116 patients. Multivariate analysis showed that macroscopical enlarged lymph node (P=0.044), number of retrieved lymph nodes (P=0.021), and perioperative blood transfusion (P=0.032) were independent prognostic factors. Haematoxylin and eosin (HE) staining indicated that enlarged lymph nodes had hyperplasia reaction. Immunohistochemistry showed that among 107 enlarged lymph nodes, 1 had macrometastases, 1 micrometastasis, 4 isolated tumor cell (ITC), and the rest 101 had no positive CK expression. Conclusion Macroscopic enlarged lymph node indicates a poor prognosis in patients with stage Ⅱ colorectal cancer.

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