A variety of managements, including systemic and local chemotherapy, radiofrequency ablation and others, are used after multidisciplinary team discussion to improve the survival of patients with unresectable liver metastasis, and to enlarge the cohort of patients who can be managed with curative intent. Patients should be divided into different clinical groups according to characteristics of the patient and tumor, and then receive different treatments. For the patients who may be converted to be resectable after chemotherapy, we should choose efficient convertible chemotherapy with short courses to get the best response rate. For KRAS wild-type patients, cetuximab combined with FOLFOX/FOLFIRI, in which 5-fluorouracil is continuously infused, is recommended. In addition, resection of the primary tumor is recommended at the right time for asymptomatic patients with unresectable liver metastases. There is no consensus on the preferred treatment modality for systemic and local therapies.
Colorectal Neoplasms ; drug therapy ; pathology ; surgery ; therapy ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; surgery

Colorectal Neoplasms ; drug therapy ; pathology ; therapy ; Humans ; Pathology, Clinical ; organization & administration ; standards

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

OBJECTIVETo establish hepatic metastasis models of two colorectal carcinoma cell lines in mice for studying mechanism involved in colorectal carcinoma metastasis and its potential countermeasures.

METHODSMurine and human colorectal carcinoma CT26 and LoVo cells were inoculated into the spleen of Balb/c mice and Balb/c nude mice, respectively. The conditions of all the mice were observed, and the survival time and liver metastases were recorded.

RESULTSAll mice inoculated with CT26 cells and a few with LoVo cells developed liver metastases without metastases in any other organs. Pathological examination identified the liver metastatic foci as poorly differentiated colonic adenocarcinoma. Compared with the mice inoculated with LoVo cells, those with CT26 cells had a higher rate of liver metastasis and a shorter survival time.

CONCLUSIONThe mouse model has been established successfully, which well mimics the pathological process of liver metastasis of colorectal cancer.

Animals ; Cell Line, Tumor ; Colorectal Neoplasms ; pathology ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Female ; Humans ; Liver ; pathology ; Liver Neoplasms ; drug therapy ; pathology ; secondary ; Mice ; Spleen ; pathology

OBJECTIVETo investigate the effect of FOLFOX4 neoadjuvant chemotherapy on the non-tumoral liver in patients with metastatic colorectal carcinoma.

METHODSA large series of surgically resected liver metastases(n=42) was selected and the morphological changes were examined by light and electron microscope. The mRNA and protein levels of connective tissue growth factor (CTGF) expression were detected by semi-quantitative RT-PCR and Western blotting analysis.

RESULTSTwelve (63.2%) of the 19 post-chemotherapy liver resection specimens had sinusoidal dilatation and hemorrhage. In contrast, 23 livers treated by surgery alone remained normal. Neoadjuvant chemotherapy could significantly enhance the mRNA and protein levels of CTGF expression in hepatic stellate cells.

CONCLUSIONSystemic FOLFOX4 neoadjuvant chemotherapy in metastatic colorectal carcinoma frequently causes morphological injuries involving hepatic microvasculature and induces CTGF expression in hepatic stellate cells to participate in hepatic fibrosis.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; pathology ; Female ; Humans ; Liver ; pathology ; Liver Neoplasms ; drug therapy ; pathology ; secondary ; Male ; Middle Aged ; Neoadjuvant Therapy

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

OBJECTIVESTo summarize the clinical experience of preoperative intraarterial chemotherapy (PRAC) and evaluate the long-term results of multimodality against colorectal cancer.

METHODSSeldinger procedure was used to intubate the tube to the artery branch which supplied blood to the tumor. The tumor was imaged to make sure the diagnosis and irrigate the chemotherapeutic drugs. Ten days after PRAC, the patients received radical operation and 6 chemotherapeutic courses with FCF regimen. Concurrent patients receiving surgical treatment yet no PRAC therapy were chosen as controls.

RESULTSOne-year survival rate was 93.05% in the PRAC group and 80.78% in the controls (P = 0.023). COX multivariate analysis was used to analyse the prognostic factors. Dukes'staging and the PRAC prescription or not were found to be independent prognostic factors of colorectal cancer patients. Patients in the PRAC group survived longer than those in the control group.

CONCLUSIONPRAC can improve the survival of colorectal cancer patients.

Antineoplastic Agents ; administration & dosage ; Colorectal Neoplasms ; drug therapy ; mortality ; pathology ; Female ; Humans ; Infusions, Intra-Arterial ; Male ; Middle Aged ; Prognosis

OBJECTIVETo discuss the biological function and regulation mechanism of curcumin in promoting human colorectal carcinoma (LoVo) cells apoptosis.

METHODConventional in vitro culture in human colorectal carcinoma cells LoVo, When 80%-90% confluence was reached, cells were treated with curcumin at different concentrations (0-20 mg x L(-1)). Curcumin's effect on cell proliferation level was examined by MTT colorimetry. The ultrastructure of curcumin-treated LoVo cells were observed with transmission electron microscope (TEM). The amount of PI-positive LoVo cells after the curcumin treatment were determined by flow cytometry. The cell apoptosis rate was detected by Annexin V-FITC/PI double staining. The mRNA level of Bax, Bcl-2, Caspase-3 and Bcl-xL were tested by means of RT-PCR.

RESULTMTT test indicates curcumin could inhibite the growth and proliferation of LoVo cells in a time- and concentration-dependent manner. TEM examination showed that curcumin can make LoVo cell morphological changes, showing the typical characteristics of apoptotic cells. Flow cytometry instrument analysis showed that curcumin can arrest cell cycle at S phase, and induce apoptosis of LoVo cells. RT-PCR test showed that curcumin can activate the expression of Bax and Caspase-3, inhibit the expression of Bcl-2 and Bcl-xL at the mRNA level.

CONCLUSIONCurcumin can significantly inhibit the proliferation and induce the apoptosis of human colorectal carcinoma cells LoVo. Such biological effect may be associated with activating Caspase-3 signal channel by activating Bax expression and inhibiting Bcl-2 and Bcl-xL expression. This study lays an important foundation for further discussing the mechanism of curcumin in inducing human colorectal carcinoma LoVo apoptosis.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colorectal Neoplasms ; drug therapy ; pathology ; Curcumin ; pharmacology ; Dose-Response Relationship, Drug ; Humans

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Colorectal Neoplasms ; pathology ; surgery ; Hepatectomy ; methods ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; surgery ; Neoadjuvant Therapy ; Preoperative Care ; Survival Rate

The aim of the present study was to accurately evaluate the association of Sox2 expression with the survival of patients with digestive tract cancers. Relevant literatures were identified by comprehensively searching databases including the Pubmed, Embase, CBMdisc, and Wanfang (up to October 2014). A meta-analysis was performed to clarify the association between Sox2 expression and overall survival or clinicopathological parameters of patients with digestive tract cancers (esophageal, gastric, and colorectal cancers). The results showed a significant association between high Sox2 expression and poor overall survival in patients with digestive tract carcinomas (HR=1.55, 95% CI=1.04-2.31), especially for patients with esophageal cancer (HR=2.04, 95%CI=1.30-3.22), colorectal cancer (HR=1.40, 95% CI=1.04-1.89), and digestive tract adenocarcinoma (HR=1.80, 95% CI=1.12-2.89), for Europeans (HR=1.98, 95% CI=1.44-2.71) or patients who did not receive neoadjuvant treatment (HR=1.73, 95% CI=1.10-2.72). Furthermore, Sox2 over-expression was highly correlated with vascular invasion (OR=1.86, 95% CI=1.25-2.77) and poor differentiation (OR=1.88, 95% CI=1.14-3.08), especially in esophageal and colorectal cancers. In conclusion, Sox2 expression may serve as a novel prognostic factor for patients with digestive tract cancers. Over-expression of Sox2 that is correlated with vascular invasion and poor differentiation suggests poor outcomes of patients with digestive tract cancers.
Antineoplastic Agents ; therapeutic use ; Biomarkers, Tumor ; genetics ; metabolism ; Colorectal Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Esophageal Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Gastrointestinal Tract ; metabolism ; pathology ; Gene Expression ; Humans ; Neoadjuvant Therapy ; methods ; Neoplasm Grading ; Neoplasms, Vascular Tissue ; diagnosis ; drug therapy ; mortality ; secondary ; Prognosis ; SOXB1 Transcription Factors ; genetics ; metabolism ; Stomach Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Survival Analysis