Peritoneal metastatic colorectal cancer (pmCRC) is common and has been considered as the terminal stage. The theory of "seed and soil" and "oligometastasis" are the acknowledged hypotheses of pathogenesis of pmCRC. In recent years, the molecular mechanism related to pmCRC has been deeply researched. We realize that the formation of peritoneal metastasis, from detachment of cells from primary tumor to mesothelial adhesion and invasion, depends on the interplay of multiple molecules. Various components of tumor microenvironment also work as regulators in this process. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been widely used in clinical practice as an established treatment for pmCRC. Besides systemic chemotherapy, targeted and immunotherapeutic drugs are also increasingly used to improve prognosis. This article reviews the molecular mechanisms and treatment strategies related to pmCRC.
Humans ; Colorectal Neoplasms/pathology* ; Combined Modality Therapy ; Peritoneal Neoplasms/secondary* ; Hyperthermia, Induced ; Colonic Neoplasms/therapy* ; Rectal Neoplasms/therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Prognosis ; Cytoreduction Surgical Procedures ; Survival Rate ; Tumor Microenvironment

Immunotherapy has been one of the hot topics in the field of colorectal cancer research in recent years. Patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) are the main beneficiaries of immunotherapy. The response rate of patients with dMMR/MSI-H colorectal cancer receiving neoadjuvant immunotherapy is nearly 100%, of which the pathological complete response rate approximately accounts for 60%-67%. The prospect of neoadjuvant immunotherapy in dMMR or MSI-H colorectal cancer patients, especially in the rectal cancer patients, lies in achieving sustainable clinical complete response so as to achieve organ preservation and avoid adverse effects on reproductive, sexual, bowel and bladder function after surgery and radiotherapy. Studies have shown that part of the colorectal cancer patients of microsatellite stability (MSS) or mismatch repair proficient (pMMR) can respond to neoadjuvant immunotherapy in combination with other treatment methods such as radiotherapy and chemotherapy. In pMMR or MSS colorectal cancer, optimizing neoadjuvant immunotherapy regimens and finding effective efficacy prediction biomarkers are important research directions. In neoadjuvant immunotherapy, overcoming primary and secondary resistance and identifying the pseudoprogression and hyperprogression of neoadjuvant immunotherapy are clinical challenges that require attention. This paper comprehensively reviews the research progress, controversies,challenges and future research directions of neoadjuvant immunotherapy (mainly immune checkpoint inhibitors) in colorectal cancer.
Humans ; Neoadjuvant Therapy/methods* ; Colorectal Neoplasms/drug therapy* ; Colonic Neoplasms/pathology* ; Immunotherapy/methods* ; DNA Mismatch Repair ; Microsatellite Instability

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*

Colorectal cancer is the third most common cancer in the world. The treatments include surgery, chemotherapy, radiotherapy and targeted therapy. The guidelines of many tumor types have been rewritten with the advent of immune checkpoint inhibitors. There are significant differences in the efficacy of immune checkpoint inhibitors in colorectal cancer according to microsatellite status. Microsatellite instability-high (MSI-H) colorectal cancer has made a breakthrough in immunotherapy, whether in the late-line, first-line, adjuvant or neoadjuvant therapy. The success of KEYNOTE-177 study has changed the guidelines with pembrolizumab becoming a standard treatment in the first-line treatment of MSI-H advanced colorectal cancer. The NICHE study, which used immunotherapy as neoadjuvant treatment of colorectal cancer, has made exciting achievements in MSI-H colorectal cancer. For microsatellite stability (MSS) colorectal cancer, many studies are ongoing, and immunotherapy is still unable to challenge the status of traditional treatment. In this paper, we review the clinical trials related to immune checkpoint inhibitors of colorectal cancer, expecting to provide references for the development of colorectal cancer immunotherapy.
Clinical Trials as Topic ; Colonic Neoplasms/drug therapy* ; Colorectal Neoplasms/pathology* ; Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Immunotherapy

With the extension of survival period and the improvement of imaging technology, the incidence of bone metastasis from colorectal cancer gradually increases. Therefore, the early diagnosis and treatment of bone metastasis should not be neglected while the primary lesion was controlled.Currently, the available evidence for bone metastasis from colorectal cancer is very limited. In this article, the Chinese Society of Colorectal Cancer organized multi-disciplinary experts to integrate the relevant studies worldwide and combine with clinical practice, focused on the issues and controversies about clinical characteristics, diagnosis and treatment, and follow-up of bone metastatic patients with colorectal cancer.After discussion and voting, Chinese expert consensus on multidisciplinary treatment of bone metastasis from colorectal cancer (2020 version) was formed. This consensus could provide clinicians with more detailed multidisciplinary treatment strategies for bone metastasis from colorectal cancer.
Asian Continental Ancestry Group ; Bone Neoplasms ; pathology ; secondary ; therapy ; China ; Colonic Neoplasms ; diagnosis ; therapy ; Colorectal Neoplasms ; diagnosis ; therapy ; Consensus ; Humans ; Interdisciplinary Communication ; Patient Care Team ; Practice Guidelines as Topic ; Treatment Outcome

Serrated polyposis syndrome (SPS) is closely associated with the initiation and development of colorectal cancer (CRC), however, there is few research on SPS in China. Serrated polyps can be divided into hyperplastic polyps, sessile serrated polyps and traditional serrated polyps. The diagnosis standard of SPS is as following: (1) There are at least 5 serrated lesions in proximal colon, and diameter of more than 2 lesions is >10 mm; (2) The patient has one serrated polyp with family history of SPS; (3) More than 20 serrated polyps can be found in the entire large bowel. The risk of SPS is relatively high in the development of colorectal cancer and 25%-70% of the SPS patients is diagnosed with synchronous or metachronous colorectal cancer during following-up. The clinical characteristics of SPS include that patients are relatively old; no significant racial difference exists in the morbidity; patients have family history of colorectal cancer. The mutation of BRAF or KRAS gene, which induces colorectal cancer through the RAS-RAF-MAPK signaling pathway, is often found in SPS as well as CpG island methylation phenotype (CIMP) and microsatellite instability (MSI). The difference between SPS and traditional familial adenomatous polyposis (FAP) should be noted because of the different pathology mechanism, clinical characteristics and the risk of malignancy. Nowadays, the common technologies of detecting serrated polyps are auto-fluorescence imaging (AFI) and narrow-band imaging (NBI), whose detective rate is around 55%. The SPS patients are advised to undergo the resection of all the serrated polyps with diameter larger than 3-5 mm and receive the colonoscopy examination every 1 or 2 year. Not only the research about SPS is on the initiation step and the molecular mechanism is still unknown, but also the scholars do not come to achieve agreement about the risk of SPS in the malignancy of colorectal cancer, which is essential for further research therefore.
Adenoma ; genetics ; pathology ; therapy ; Adenomatous Polyposis Coli ; genetics ; pathology ; therapy ; Colonic Polyps ; Colonoscopy ; Colorectal Neoplasms ; genetics ; pathology ; therapy ; DNA Methylation ; Genes, ras ; Humans ; Microsatellite Instability ; Mutation ; Phenotype ; Proto-Oncogene Proteins B-raf ; Syndrome

OBJECTIVE To explore downstream regulatory pathway of microRNA-21 (miR-21) in colon cancer cells (RKO) through detecting miR-21 and its target PDCD4, and the influence of miR-21 regulation on the sensitivity of RKO cells to 5-fluorouracil (5-FU). METHODS 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the effect of 5-FU on the viability of RKO cells with knockout of miR-21 or high expression of PDCD4. Real-time was used to determine the expression of PDCD4, ABCC5 and CD44 in RKO cell after knockout of miR-21. RESULTS MTT assay reveals that the IC50 of 5-FU in RKO-WT cells (52.82 ± 0.06 umol/L) was about 67% higher than in miR-21 knockout cells (32.23 ± 0.05 umol/L) (P < 0.05), and the apoptosis ratio elevated after knockout of miR-21. High expression of PDCD4, a target gene of miR-21, can negatively regulate the expression of ABC transporter ABCC5 and the stem cell marker CD44. CONCLUSION MiR-21 can mediate the drug resistance to 5-FU by inhibiting its target PDCD4, which can regulate the expression of ABCC5 and CD44 genes.
ATP Binding Cassette Transporter, Sub-Family G, Member 5 ; ATP-Binding Cassette Transporters ; genetics ; Antimetabolites, Antineoplastic ; pharmacology ; Apoptosis Regulatory Proteins ; physiology ; Cell Line, Tumor ; Colonic Neoplasms ; drug therapy ; pathology ; Drug Resistance, Neoplasm ; Fluorouracil ; pharmacology ; Humans ; Hyaluronan Receptors ; genetics ; Lipoproteins ; genetics ; MicroRNAs ; physiology ; RNA-Binding Proteins ; physiology

Primary colorectal choriocarcinoma is a rare neoplasm. Only 19 cases have been reported worldwide, most of which involved adenocarcinomas. The prognosis is usually poor, and the standard therapy for this tumor has not been established. A 61-year-old woman presented with constipation and lower abdominal discomfort. She was diagnosed with primary adenocarcinoma with focal choriocarcinomatous differentiation in the sigmoid colon and liver metastasis. Because the serum beta-human chorionic gonadotropin level was not significantly elevated, and because only focal choriocarcinomatous differentiation was diagnosed, we selected the chemotherapy regimen that is used for the treatment of metastatic colorectal adenocarcinoma. The patient survived for 13 months after the initial diagnosis. This is the first case in Korea to assess the suppressive effects of the standard chemotherapy for colorectal adenocarcinoma against coexisting colorectal choriocarcinoma and adenocarcinoma.
Adenocarcinoma/*diagnosis/drug therapy/pathology ; Antineoplastic Agents/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; CA-19-9 Antigen/analysis ; Chorionic Gonadotropin, beta Subunit, Human/blood ; Colon, Sigmoid/pathology ; Colonic Neoplasms/*diagnosis/drug therapy/pathology ; Colonoscopy ; Constipation/etiology ; Female ; Fluorouracil/therapeutic use ; Humans ; Leucovorin/therapeutic use ; Liver Neoplasms/secondary ; Middle Aged ; Organoplatinum Compounds/therapeutic use ; Prognosis ; Tomography, X-Ray Computed

No abstract available.
Angiogenesis Inhibitors/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/administration & dosage ; Camptothecin/analogs & derivatives/therapeutic use ; Colonic Neoplasms/*diagnosis/drug therapy/pathology ; Colonoscopy ; Female ; Fluorouracil/therapeutic use ; Humans ; Leucovorin/therapeutic use ; Liver Neoplasms/drug therapy/pathology/secondary ; Lung Neoplasms/drug therapy/pathology/secondary ; Middle Aged ; Positron-Emission Tomography ; Tomography, X-Ray Computed