BACKGROUND:Neoadjuvant immune checkpoint blockade has shown remarkable activity in mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H), locally advanced colorectal cancer. Preclinical studies suggest that COX-2 inhibition might modulate the inflammatory tumour microenvironment and augment the effect of PD-1 blockade. We aimed to investigate whether the addition of the COX-2 inhibitor celecoxib to neoadjuvant toripalimab would increase the pathological complete response in this population. METHODS:PICC-2 was a multicentre, open-label, randomised, controlled, phase 2 trial conducted at three academic hospitals in China. Eligible patients were aged 18-75 years; had histologically confirmed dMMR or MSI-H colorectal cancer, of clinical stage T3-T4 or any clinical T stage with lymph node positivity (N+); had an Eastern Cooperative Oncology Group performance status score of 0 or 1; and had adequate haematological, hepatic, and renal function. Participants were randomly assigned (1:1) via an interactive web response system, stratified by tumour location and clinical T stage, to receive neoadjuvant toripalimab plus celecoxib or toripalimab monotherapy every 14 days for 12 cycles, followed by surgery. Toripalimab 3 mg/kg was administered intravenously on day 1 in both groups; patients in the toripalimab plus celecoxib group also received celecoxib 200 mg orally twice daily on days 1-14. The primary endpoint was the proportion of patients with pathological complete response, defined as no presence of residual viable tumour in the primary tumour and all sampled lymph nodes at surgery, assessed by central blinded independent pathological review in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03926338, and is ongoing. FINDINGS:Between May 5, 2022, and Jan 20, 2025, 110 patients were randomly assigned to toripalimab plus celecoxib (n=55) or toripalimab monotherapy (n=55). Overall, 65 (59%) patients were male, all patients were Chinese, 76 (69%) had cT4 tumours, and 105 (95%) had clinically node-positive disease. At the data cutoff date (Oct 10, 2025), median follow-up was 18·1 months (IQR 11·5-25·3). 49 (89%) of 55 patients in each group completed all 12 planned cycles of neoadjuvant therapy. Surgery was done in 53 (96%) of 55 patients in the toripalimab plus celecoxib group and 51 (93%) of 55 in the monotherapy group. Pathological complete response was observed in 49 of 55 patients (89% [95% CI 78-96]) in the toripalimab plus celecoxib group versus 38 of 55 (69% [55-81]) in the monotherapy group (between-group difference 19 percentage points [95% CI 4-34]; p=0·014). Grade 3 treatment-related adverse events occurred in three (5%) patients and four (7%) patients, respectively; grade 3 treatment-related adverse events were tumour perforation (two [4%]) and bowel obstruction (one [2%]) in the toripalimab plus celecoxib group, and rash (one [2%]), tumour perforation (one [2%]), increased aminotransferase (one [2%]), and hypothyroidism (one [2%]) in the monotherapy group. No grade 4 or 5 treatment-related adverse events occurred. INTERPRETATION:In patients with dMMR or MSI-H locally advanced colorectal cancer, neoadjuvant toripalimab plus celecoxib significantly increased the proportion of patients attaining pathological complete response compared with toripalimab monotherapy, with a similar safety profile. These findings support further investigation of this combination strategy in larger phase 3 trials. FUNDING:The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research, the National Key Clinical Discipline of China, the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases, and the Chinese Society of Clinical Oncology-Junshi Biosciences Oncology Immunity Research. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.
BACKGROUND:The efficacy of neoadjuvant chemotherapy combined with dual immune checkpoint blockade in proficient mismatch repair/microsatellite-stable (pMMR/MSS) locally advanced colorectal cancer (LACRC) remains uncertain. METHODS:In this open-label, randomized phase 2 trial (ClinicalTrials.gov: NCT05571644), eligible patients were randomly assigned (1:1:1) to receive 6 cycles of neoadjuvant mFOLFOXIRI plus cadonilimab, mFOLFOXIRI, or mFOLFOX6, followed by surgery and adjuvant chemotherapy. The primary endpoint was pathological complete response (pCR) in the intention-to-treat population. Secondary endpoints included major pathological response (MPR), safety, locoregional recurrence, disease-free survival, and overall survival. FINDINGS:Between July 2023 and August 2024, 123 patients were randomly assigned (41 per group). Neoadjuvant mFOLFOXIRI plus cadonilimab significantly improved pCR compared with mFOLFOX6 (26.8% versus 9.8%; odds ratio [OR], 3.4; 95% confidence interval [CI], 1.04 to 13.24; p = 0.046), whereas mFOLFOXIRI alone did not (14.6% versus 9.8%; OR, 1.6; 95% CI, 0.4 to 6.7; p = 0.50). MPR rates were 68.3%, 46.3%, and 43.9%, respectively, and were significantly higher with mFOLFOXIRI plus cadonilimab than with mFOLFOX6 (p = 0.026). Downstaging to ypStage 0-I occurred in 66%, 45%, and 41% of patients in the three groups, respectively, and was significantly higher in the mFOLFOXIRI plus cadonilimab group (p = 0.027). Grade ≥3 adverse events were manageable, with liver enzyme elevation and neutropenia being the most common. CONCLUSIONS:Neoadjuvant mFOLFOXIRI plus cadonilimab significantly improved pCR compared with mFOLFOX6 in LACRC, with a manageable safety profile, supporting further investigation. FUNDING:This work was funded by the National Science Fund for Distinguished Young Scholars (82425045) and the National Natural Science Foundation of China (82272800).
Intratumoral microbiota plays a crucial role in cancer progression. However, the relationship between host genetics and intratumoral microbiota, as well as their interaction in colorectal cancer (CRC) progression, remains unclear. With 748 Chinese CRC patients enrolled from three cohorts, we find that the single nucleotide polymorphism (SNP) rs2355016, located in the intron of ATP-sensitive inward rectifier potassium channel 11 (KCNJ11), is significantly associated with the abundance of Fusobacterium. Compared with the rs2355016 GG genotype, patients carrying the A allele exhibit downregulation of KCNJ11 and enrichment of Fusobacterium, which corresponds to accelerated proliferation and progression. Low expression of KCNJ11 can increase the level of galactose-N-acetyl-d-galactosamine (Gal-GalNAc) on the surface of CRC cells, thereby facilitating the binding of the Fap2 protein from F. nucleatum to Gal-GalNAc. This further enhances the adhesion and invasion of F. nucleatum and promotes CRC growth. Our study explores the interaction between intratumoral microbiota and SNPs in CRC patients, which will enhance our understanding of CRC proliferation.
Microwave ablation (MWA) is widely used to eliminate colorectal liver metastases (CRLM). However, the risk of tumor recurrence is difficult to predict due to lack of reliable clinical and biological markers. Elevation of gamma-glutamyl transferase (GGT) and aspartate transaminase (AST) provides signals for liver inflammation and cancer progression. The present study evaluated the association between pre-ablation GGT to AST ratio index (GSR) and hepatic recurrence in patients with CRLM after MWA. A retrospectively analyzed 192 CRLM patients who underwent MWA from January 2013 to December 2017. Pre-ablation GSR was classified into high (≤ 2.34) or low (> 2.34) using the upper quartile value. The prognostic value of GSR and other risk factors for liver progression-free survival (LPFS) and cancer-specific survival (CSS) were evaluated by univariate and multivariate analyses. High GSR was significantly associated with males (P = 0.041), the presence of cholelithiasis (P = 0.012), but not pre-ablation chemotherapy (P = 0.355), which caused significantly increased levels of GGT (P = 0.015) and AST (P = 0.008). GSR showed a significant association with LPFS and CSS through univariate analysis (P = 0.002 and 0.006) and multivariate analysis (P = 0.043 and 0.037). The subgroup analysis demonstrated no interaction between GSR and all variables except for distribution in the sub-analysis of LPFS. Our findings suggest that the pre-ablation GSR can be considered as a promising prognostic indicator for poor prognosis of patients with CRLM underwent MWA. Not applicable.
Background & aims Gut microbiota is closely related to the occurrence and development of colorectal cancer (CRC). However, the differences in bacterial co-abundance groups (CAGs) between tumor tissue (TT) and normal tissue (NT), as well as their associations with clinical features, are needed to be clarified. Methods Bacterial 16 S rRNA sequencing was performed by using TT samples and NT samples of 251 patients with colorectal cancer. Microbial diversity, taxonomic characteristics, microbial composition, and functional pathways were compared between TT and NT. Hierarchical clustering was used to construct CAGs. Results Four CAGs were grouped in the hierarchical cluster analysis. CAG 2, which was mainly comprised of pathogenic bacteria, was significantly enriched in TT samples (2.27% in TT vs. 0.78% in NT, p < 0.0001). CAG 4, which was mainly comprised of non-pathogenic bacteria, was significantly enriched in NT samples (0.62% in TT vs. 0.79% in NT, p = 0.0004). In addition, CAG 2 was also significantly associated with tumor microsatellite instability (13.2% in unstable vs. 2.0% in stable, p = 0.016), and CAG 4 was positively correlated with the level of CA199 (r = 0.17, p = 0.009). Conclusions Our research will deepen our understanding of the interactions among multiple bacteria and offer insights into the potential mechanism of NT to TT transition.
AbstractBackgroundThe relationship between the radiological lymph node (rLN) size and survival outcome in node‐negative rectal cancer is still uncertain. In this study, we aimed to explore the role of enlarged rLN in predicting the survival of node‐negative rectal cancers.MethodsWe retrospectively reviewed the records of 722 node‐negative rectal cancer who underwent curative resection. Factors associated with DFS (disease‐free survival) and CSS (cancer‐specific survival) were assessed with univariate and multivariate analysis. Survival analysis was performed according to presence with or without enlarged rLN. Combining rLN with NLR as a new index‐inflammation immune score (IIS) for predicting survival. Comparing different models to assess the predictive powers.ResultsA total of 119 patients had tumor recurrence and 73 patients died due to cancer. Patients with enlarged rLN (≥5 mm) was significantly associated with better DFS (HR:0.517, 95%CI:0.339–0.787, p = 0.002) and CSS (HR:0.43, 95%CI:0.242–0.763, p = 0.004). The risk factors of recurrence were rLN, neutrophil‐lymphocyte ratio (NLR), CEA level, and distance from the anal verge. The risk of recurrence increased by 1.88‐ and 2.83‐fold for the high score in IIS compared with the low and intermediate score group (All p < 0.001). Similarly, the high score in IIS also increased the risk of cancer‐specific death. In the model comparison, the AIC and LR were improved by including the rLN into the NLR model for DFS and CSS prediction (All p < 0.05).ConclusionsNode‐negative rectal cancer patients with enlarged rLN had a better survival outcome. IIS might be a more comprehensive and complete inflammation immune index for survival prediction.
The tumour microenvironment (TME) and immunosuppression play an important role in colon cancer (CC) metastasis, which seriously affects the prognosis of CC. G protein subunit gamma 4 (GNG4) has been shown to participate in tumour progression and the tumour mutation burden (TMB) in colorectal cancer. However, the effect of GNG4 on the CC TME and immunology remains elusive. Weighted gene coexpression network analysis (WGCNA) was employed for screening aberrantly expressed genes associated with the immune score, and GNG4 was then selected through prognostic and immune correlation analysis. Based on RNA sequencing data obtained from the TCGA and GEO databases, the expression pattern and immune characteristics of GNG4 were comprehensively examined using a pan-cancer analysis. Upregulation of GNG4 was linked to an adverse prognosis and immune inhibitory phenotype in CC. Pan-cancer analysis demonstrated higher GNG4 expression in tumours than in paired normal tissue in human cancers. GNG4 expression was closely related to prognosis, TMB, immune checkpoints (ICPs), microsatellite instability (MSI) and neoantigens. GNG4 promoted CC cell proliferation, migration and invasion and participated in immune regulation in the TME. Significantly, GNG4 expression was found to negatively correlate with tumour-infiltrating immune cells, ICP, TMB and MSI in CC. GNG4 expression predicted the immunotherapy response in the IMvigor210 cohort, suggesting that GNG4 could be used as a potential biomarker in CC for prognostication and immunology. Moreover, the expression of GNG4 predicted the immunotherapy response of ICB in CC.
Purpose:Previous studies on the effect of hepatitis B virus (HBV) infection on colorectal liver metastasis (CRLM) are contradictory. This study revealed different, more specific impacts of HBV on CRLM.Patients and Methods:A total of 3132 colorectal cancer patients treated from 2013 to 2015 were analyzed retrospectively and followed up for five years. The patients were divided into three groups: group A (chronic HBV infection, CHB); group B, (occult HBV infection, OHB) and group C (no HBV infection, NHB). The risk factors for CRLM, 5-year overall survival (OS), and liver disease-free survival (LDFS) were analyzed.Results:A total of 905 patients (28.9%) had CRLM, with poor survival compared to those without CRLM (P < 0.01). The incidence of CRLM was 33.41% (138/413) in group A, 21.63% (138/638) in group B and 30.23% (629/2081) in group C (P < 0.05). Synchronous colorectal cancer liver metastasis (SYN-CRLM) was found in 425 patients (13.57%). CHB increased the risk of SYN-CRLM (P < 0.01), with a worse prognosis (P < 0.05). Metachronous colorectal cancer liver metastasis (MET-CRLM) was found in 480 patients (15.33%). OHB decreased the risk of MET-CRLM after surgery (P = 0.02), with a better 5-year LDFS (P = 0.01). Even without surgery, patients with OHB showed a lower incidence rate of MET-CRLM (P < 0.01).Conclusion:The incidence of CRLM in this study was approximately 28.9%. Surgery and different HBV infection statuses affected the occurrence of CRLM. Chronic HBV infection increased the risk of SYN-CRLM with poor prognosis. Occult HBV infection reduced the risk of MET-CRLM with better LDFS after surgery.
[目的]既往有多个报道结直肠癌转移方式的研究,但尚缺少基于长期随访并以死亡作为观察终点,总结CRC转移部位、发生率以及相关生存数据的研究.[方法]本研究回顾中山大学附属第六医院373例结直肠癌死亡患者资料,统计分析肿瘤转移的部位、发生率以及生存资料.[结果]334例(89.5%)患者为肿瘤相关性死亡,肝转移率为51.5%,肺转移率为40.4%,腹膜转移率为55.7%.单纯肝、肺、腹膜转移患者数分别为27例(8%)、21例(6.3%)、63例(18.9%).单纯肺转移患者生存明显优于单纯肝转移或单纯腹膜转移(P<0.01).肝肺腹膜同时转移的患者共66例(19.7%)且预后最差(P<0.01).[结论]并非所有死亡结直肠癌患者都会出现肝肺腹膜同时转移.不同患者的转移方式存在差异,并与生存相关.
目的:评估三七化痔丸联合马应龙麝香痔疮膏治疗痔疮的临床效果及安全性.方法:采用随机、双盲、安慰剂平行对照的研究设计.选取在中山大学附属第六医院接受诊治的痔疮患者150例,随机将患者平均分为试验组75例、对照组75例.试验组给予三七化痔丸治疗,对照组给予安慰剂治疗,两组均加用马应龙麝香痔疮膏治疗.记录治疗前、治疗7 d、14 d两组患者的痔核表面黏膜、痔核大小、外痔肿胀、外痔大小等观察指标评分,同时观察不良反应,并比较两组的疗效和安全性.结果:试验组和对照组分别有58例和67例完成治疗.试验组治疗7 d外痔肿胀、外痔大小评分,以及治疗14 d痔核表面黏膜、痔核大小评分均显著低于对照组(P<0.05);SF-36量表评分及不良反应发生率组间差异无统计学意义(P>0.05).结论:三七化痔丸联合马应龙麝香痔疮膏治疗痔疮可显著改善外痔红肿、缩小外痔体积.另外,在停用马应龙麝香痔疮膏后继续口服三七化痔丸可显著缓解痔核表面黏膜充血、隆起,缩小痔核体积.本治疗方案疗效确切,有利于改善病情,且安全性良好,值得临床推广.
Background PD-1 blockade is highly effective in patients with mismatch repair-deficient or microsatellite instability-high metastatic colorectal cancer. The role of single-agent PD-1 blockade in the neoadjuvant setting for resectable mismatch repair-deficient or microsatellite instability-high colorectal cancer remains unclear. We investigated the efficacy and safety of PD-i blockade with toripaliunab, with or without the COX-2 inhibitor celecoxib, as neoadjuvant treatment for mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancers. Methods The PD-1 Inhibitor in Microsatellite Instability Colorectal Cancer (PICC) trial was a single-centre, open-label, parallel-group, non-comparative, randomised, phase 2 study undertaken at the Sixth Affiliated Hospital of Sun Yatsen University (Guangzhou, China). Eligible patients were aged 18-75 years, had histologically confirmed mismatch repair-deficient or microsatellite instability-high colorectal cancer, had clinical stage T3-T4 or any T with lymph node positivity (N+). Eastern Cooperative Oncology Group performance score of 0 or 1, and adequate haematological, hepatic, and renal function. Participants were randomly assigned (1:1), without any stratification or balanced blocking, to receive toripalimab 3 mg/kg intravenously on day 1, with or without celecoxib 200 mg orally twice daily from day 1 to 14 of each 14-day cycle, for six cycles before surgical resection. Adjuvant treatment with toripalimab with or without celecoxib was permitted at the investigators' discretion. The primary endpoint was the proportion of patients with pathological complete response, defined as tumours without any viable tumour cells in the resected primary tumour sample and all sampled regional lymph nodes. All efficacy and safety analyses were assessed in the modified intention-to-treat population, which included all patients who were randomly assigned to treatment and who received at least one dose of toripalimab. This trial is registered with ClinicalTrials.gov , NCT03926338, and is ongoing. Findings Between May 1,2019, and April 1,2021,53 patients were screened, of whom 34 were randomly assigned to either the toripalimab plus celecoxib group (n=17) or the toripalimab monotherapy group (n=17). As of data cutoff (Aug 10, 2021), median follow-up was 14.9 months (IQR 8-8-17-0). All patients received study treatment and underwent surgical resection; there were no treatment-related surgical delays. All 34 patients had an RO resection (>1 mm resection margin). 15 of 17 patients (88% [95% CI 64-99]) in the toripalimab plus celecoxib group and 11 of 17 patients (65% [38-86]) in the toripalimab monotherapy group had a pathological complete response. All patients continued to receive adjuvant toripalimab with or without celecoxib for a total perioperative duration of 6 months and were alive and free of recurrence at data cutoff. During neoadjuvant treatment, ten (59%) patients in the toripalimab plus celecoxib group and ten (59%) in the toripalirnab monotherapy group had grade 1-2 treatment-related adverse events. Only one (3%) of 34 patients, who was in the toripalimab plus celecoxib group, had a grade 3 or higher treatment-related adverse event during the neoadjuvant phase, which was grade 3 increased aspartate aminotransferase levels. In the adjuvant phase, only one (3%) of 34 patients, who was in the toripalimab monotherapy group, had a grade 3 or higher treatment-related adverse events, which was grade 3 increased aspartate aminotransferase and alanine aminotransferase levels. Interpretation Neoadjuvant toripalimab with or without celecoxib could be a potential therapeutic option for patients with mismatch repair deficient or microsatellite instability-high, locally advanced, colorectal cancer. This treatment was associated with a high pathological complete response rate and an acceptable safety profile, which did not compromise surgery. Longer term follow-up is needed to assess effects on survival-related endpoints. Copyright (C) 2021 Elsevier Ltd. All rights reserved.
Background: There is still a lack of nomograms that can accurately predict liver metastasis and poor prognosis after neoadjuvant therapy for locally advanced rectal cancer (LARC). Effective nomograms may help clinicians better identify LARC patients with potential high-risk risks, so as to carry out more targeted monitoring, treatment and follow-up. Methods: The nomograms were based on the FOWARC trial (NCT01211210), which included 302 LARC patients who underwent neoadjuvant treatment before surgery at the Sixth Affiliated Hospital of Sun Yatsen University from 2011 to 2014. The predictive accuracy and discriminative ability of the nomograms were determined by the concordance index (C-index) and calibration curve. The results were validated using bootstrap resampling and a prospective study on 1(X) patients in 2017. Results: The 3-year liver disease-free survival (LDFS) rate after neoadjuvant treatment for LARC was 91.65% (training cohort 92.22%, validation cohort 90.01%). Factors associated with LDFS were hepatitis B virus (HBV) infection, anemia, lymph node number, postoperative T stage and tumor nodule, which were all included in the nomogram for LDFS. The C-indies of the nomogram for LDFS were 0.828 and 0.845 in the training and validation cohorts. The 3-year overall survival (OS) rate was 94.14% (training cohort 94.13%, validation cohort 94.05%). Factors in the nomogram for OS were mesorectal fascia involvement (MRF), postoperative N stage, pathological differentiation, tumor nodule and neural invasion. The C-indies of the nomogram for predicting OS were 0.73 and 0.774 in the training and validation cohorts. The calibration curve for the survival probability showed good agreement between the nomogram predictions and the actual observations. Conclusions: The nomograms established in this study can effectively predict LDFS and has good clinical application potential for OS in LARC patients treated with neoadjuvant therapy.
Objective: To investigate the risk factors associated with intrahepatic recurrence and survival after microwave ablation (MWA) for colorectal cancer with liver metastases. Methods: Retrospective analysis of clinical, pathological and follow-up data of 60 patients who underwent ultrasound-guided microwave ablation for treating liver metastases from January 2013 to December 2015 at the Sixth Affiliated Hospital, Sun Yat-Sen University, with Cox univariate and multifactorial regression analyses of risk factors affecting intrahepatic recurrence and overall survival after ablation of liver metastases. Results: After follow-up for 12.5 to 47.4 months, intrahepatic recurrence occurred in 26 cases, of which 6.1% (7/114) showed local tumor progression at the original ablation site; 11 cases died for tumor-related reasons. Multi-factor Cox regression analysis showed that age ≥60 years and maximum diameter of liver metastases ≥2 cm were independent risk factors for patients to develop intrahepatic recurrence after surgery. HBsAb positivity and chemotherapy after ablation until intrahepatic recurrence are independent protective factors for patients developing intrahepatic recurrence after surgery. Multi-factor Cox regression analysis showed that the number of liver metastases ≥3 was an independent risk factor for overall survival. Conclusion: After microwave ablation for patients with colorectal cancer liver metastases, patients aged ≥60 years, HBsAb negative and with maximum liver metastases ≥2 cm in diameter were more likely to have recurrent intrahepatic metastases, while aggressive chemotherapy after ablation was effective in reducing recurrent intrahepatic metastases, and the number of liver metastases ≥3 indicated a poor overall prognosis.
Background: Previous studies on the effect of HBV infection on CRLM are contrary. This study identified more specific and different impacts of HBV on CRLM. Methods: A total of 3132 CRC patients were analyzed retrospectively and followed up for five years. All patients were divided into three groups: group A, HBsAg positive with HBV infection; group B, HBsAg negative with HBV infection; and group C, no HBV infection. The risk factors for SYN-CRLM, MET-CRLM, 5-year OS, and LDFS were analyzed. Results: A total of 829 patients had CRLM. SYN-CRLM was found in 425 patients. The incidence of SYN-CRLM was 16.95%, 11.60% and 13.50% (P <0.03) in groups A, B, and C, respectively. HBsAg-positive HBV infection increased the risk of SYN-CRLM (P<0.01), with a worse prognosis in group A (P<0.05). MET-CRLM was found in 404 patients. The incidence of MET-CRLM in groups A, B, and C, was 16.51%, 11.53% and 16.50% (P=0.02). HBsAg-negative HBV infection decreased the incidence of MET-CRLM (P=0.02) with a better 5-year LDFS (P=0.01), but was not related to 5-year OS (P=0.15). Conclusion: HBsAg positivity infection increased the risk of SYN-CRLM with poor prognosis. HBsAg-negative infection reduced the risk of MET-CRLM with better LDFS after surgery.
Background The incidence of anal squamous cell carcinoma (SCC) has been steadily growing globally in the past decade. Clinical data on anal SCC from China are rare. We conducted this study to describe the clinical and epidemiological characteristics of anal SCC in China and explore prognostic factors of outcomes among patients with anal SCC. Methods We audited demographic characteristics, relevant symptoms, risk factors, treatment modalities and outcomes for patients diagnosed with anal SCC at 11 medical institutions in China between January 2007 and July 2018. Results A total of 144 patients (109 females) were diagnosed with SCC during this period. Median age at initial diagnosis was 52.0 (interquartile range: 46.0–61.8) years. The most common symptoms were bleeding ( n = 93, 64.6%), noticing a lump ( n = 49, 34.0%), and pain ( n = 47, 32.6%). The proportion of patients at the American Joint Committee on Cancer (AJCC) stages I-IV were 10 (6.9%), 22 (15.3%), 61 (42.4%) and 8 (5.6%), respectively, and AJCC stages in 43 (29.9%) patients were unknown. Thirty-six patients (25.0%) underwent abdominoperineal resection initially. Univariable analysis showed that T stage predicted recurrence-free survival (RFS) (Hazard ratio [HR] = 3.03, 95% Confidence interval [CI]: 1.10–8.37, p = 0.032), and age group (HR = 2.90, 95% CI: 1.12–7.49, p = 0.028), AJCC stage (HR = 4.56, 95% CI: 1.02–20.35, p = 0.046), and N stage (HR = 3.05, 95% CI: 1.07–8.74, p = 0.038) predicted overall survival (OS). Conclusions T stage was identified as prognostic factor of RFS, and age, AJCC stage, and N stage were identified as prognostic factors of OS. Improving symptom awareness and earlier presentation among patients potentially at risk for anal SCC should be encouraged. Familiarity with the standard treatment among health care providers in China should be further improved.
Purpose To analyze whether HBV infection can reduce the risk of colorectal liver metastasis (CRLM) in stage 2 colorectal cancer (CRC). Methods The data of postoperative pathological stage 2 CRC patients treated at the Sixth Affiliated Hospital of Sun Yat-sen University between 2013 and 2015 were analyzed. The patients were divided into an infection group (group A) and a non-infection group (group B). The correlations between HBV infection and CRLM, 5-year liver disease-free survival, and 5-year overall survival were compared. Results A total of 884 patients who met the inclusion criteria were included in the study. Group A included 297 patients (33.60%), and 5 patients (1.68%) had CRLM. Group B included 587 patients (66.40%), and 31 patients (5.28%) had CRLM. The results of correlation analysis and logistic regression analysis showed that HBV infection (P = 0.013, HR = 0.29, 95% CI 0.11-0.77) was a protective factor for CRLM, while CEA > 5 ng/ml (P = 0.002, HR = 3.12, 95% CI 1.51-6.47) and hypertension (P = 0.010, HR = 3.50, 95% CI 1.34-9.09) were risk factors for CRLM. Group A had a significantly better 5-year liver disease-free survival than group B (P = 0.011, HR = 0.31, 95% CI 0.16-0.63), but there was no significant difference in the 5-year overall survival (P = 0.433). Conclusion HBV infection may reduce the risk of metachronous liver metastasis in stage 2 colorectal cancer.
PURPOSE:This trial evaluated the addition of cetuximab to a modified FOLFOXIRI (mFOLFOXIRI: 5-fluorouracil/folinic acid, oxaliplatin, irinotecan) as conversion therapy in a two-group, nonrandomized, multicenter, phase II trial in patients with initially technically unresectable colorectal liver-limited metastases (CLM) and BRAF/RAS wild-type.PATIENTS AND METHODS:Patients were enrolled to receive cetuximab (500 mg/m2 ) plus mFOLFOXIRI (oxaliplatin 85 mg/m2 , irinotecan 165 mg/m2 , folinic acid 400 mg/m2 , 5-fluorouracil 2,800 mg/m2 46-hour infusion, every 2 weeks) (the cetuximab group) or the same regimen of mFOLFOXIRI alone (the control group), in a 2:1 ratio allocation. The primary endpoint was the rate of no evidence of disease (NED) achieved. Secondary endpoints included resection rate, objective response rate (ORR), survival, and safety.RESULTS:Between February 2014 and July 2019, 117 patients were registered for screening at six centers in China, and 101 of these were enrolled (67 cetuximab group, 34 control group). The rate of NED achieved was 70.1% in the cetuximab group and 41.2% in the control group (difference 29.0%; 95% confidence interval [CI], 9.1%-48.8%; p = .005). Patients in the cetuximab group had improved ORR (95.5% vs. 76.5%; difference 19.1%; 95% CI, 17.4%-36.4%; p = .010) compared with those in control group. Progression-free survival and overall survival showed the trend to favor the cetuximab group. The incidence of grade 3 and 4 adverse events was similar in the two groups.CONCLUSION:Addition of cetuximab to mFOLFOXIRI improved the rate of NED achieved. This combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable CLM.IMPLICATIONS FOR PRACTICE:This trial evaluated the addition of cetuximab to a modified FOLFOXIRI as conversion therapy in a phase II trial in patients with initially technically unresectable colorectal liver-limited metastases and BRAF/RAS wild-type. The rate of no evidence of disease achieved was 70.1% in the cetuximab plus modified FOLFOXIRI group and 41.2% in the modified FOLFOXIRI group. Objective response rates, overall survival, and progression-free survival were improved in the cetuximab group when compared with the modified FOLFOXIRI group. Addition of cetuximab to modified FOLFOXIRI increased the rate of no evidence of disease achieved, and this combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable colorectal liver-limited metastasis.
目的 探讨微波消融(MWA)治疗结直肠癌肝转移灶后肝内复发和生存的相关危险因素.方法 回顾性分析中山大学附属第六医院2013年1月至2015年12月行结直肠癌肝转移灶超声引导下微波消融治疗的60例患者的临床、病理及随访资料,对影响肝转移灶消融后肝内复发和总生存的危险因素进行Cox单因素和多因素回归分析.结果 随访12.5~47.4个月,其中有26例发生肝内复发,其中6.1%(7/114)原消融灶出现局部肿瘤进展;11例出现肿瘤相关死亡.多因素Cox回归分析结果显示,年龄≥60岁和肝转移灶最大直径≥2 cm是患者术后发生肝内复发的独立危险因素;HBsAb阳性和消融后至肝内复发前有化疗是患者术后发生肝内复发的独立保护因素.多因素Cox回归分析结果显示,肝转移灶个数≥3个是影响患者总生存的独立危险因素.结论 结直肠癌肝转移患者行肝转移灶微波消融治疗后,年龄≥60岁、HBsAb阴性和肝转移灶最大直径≥2 cm的患者更容易再发肝内转移,而消融后的积极化疗则可有效降低再发肝内转移,肝转移灶个数≥3个提示总体预后不良.
目的 探讨腹腔引流液中降钙素原和CRP水平对判断腹腔镜Dixon直肠癌根治术后患者发生吻合口瘘的预测价值.方法 收集80例接受腹腔镜Dixon直肠癌根治术的患者临床资料,记录术后吻合口瘘发生情况.根据是否发生吻合口瘘分为观察组(有吻合口瘘)和对照组(无吻合口瘘),分别于术后当日、术后第3日及第5日检测并比较两组患者腹腔引流液中降钙素原和CRP水平,并绘制受试者工作特征(ROC)曲线评估腹腔引流液中降钙素原和CRP水平对预测术后吻合口瘘的价值.结果 接受腹腔镜Dixon直肠癌根治术的80例患者中,发生吻合口瘘5例(6%),该5例纳入观察组,余75例未发生吻合口瘘者纳入对照组.观察组术后肛门排气时间和术后住院时间均较对照组延长(P均<0.05).术后第3日和第5日观察组患者腹腔引流液中降钙素原和CRP水平均高于对照组(P均<0.05).ROC分析结果显示,术后第3日腹腔引流液中降钙素原水平和术后第5日CRP水平对预测吻合口瘘具有较高的准确性,其对应的AUC最大,分别为0.845(与术后当日及术后第5日比较P均<0.05)、0.855(与术后当日及术后第3日比较P均<0.05),灵敏度分别为0.835、0.875,特异度分别为0.762、0.773.结论 Dixon直肠癌根治术后动态监测腹腔引流液中降钙素原和CRP水平,尤其是监测术后第3日时的降钙素原水平和术后第5日时CRP水平对预测吻合口瘘具有较高价值.