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

OBJECTIVETo evaluate the short-term therapeutic effects and side effects of combined hydroxycamptothecine and oxaliplatin in the treatment of advanced digestive tract cancers.

METHODSThirty patients suffering from advanced digestive tract tumors including gastric cancer 8, colorectal cancer 20, cholecystic cancer 1 and malignant fibroadenoma 1 were studied. They were treated with hydroxycamptothecine plus oxaliplatin for 2 cycles with interval of 21 days.

RESULTSThe complete response, partial response, stable disease and progressive disease rates were 3.3% (1/30), 36.7% (11/30), 53.3% (15/30) and 6.7% (3/30) respectively with an overall response rate (CR + PR) of 40.0% (12/30). In the whole 77 cycles, leukocytopenia was observed in 34 cycles (44.2%) and 19 cycles (55.9%) at grades III and IV. Diarrhea developed in 42 cycles (54.5%) and 20 cycles (47.6%) grades III and IV. The other side effects were fever, alopecia, nausea and vomiting, constipation, hepatic and renal function abnormity and neuritis.

CONCLUSIONSatisfactory response rate is obtainable in advanced colorectal cancer as treated by hydroxycamptothecine plus oxaliplatin. The toxicity consists of severe leukocytopenia and diarrhea.

Adenocarcinoma ; drug therapy ; secondary ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; analogs & derivatives ; Colorectal Neoplasms ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Female ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; administration & dosage ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology ; Treatment Outcome

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

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

OBJECTIVETo evaluate safety and effect of percutaneous chemotherapy pump placement for portal vein chemotherapy in management of colorectal cancer with hepatic metastasis.

METHODSTwenty-three cases of colorectal cancer with liver metastasis were treated with percutaneous chemotherapy pump placement for portal vein chemotherapy, and the therapeutic effect of this treatment was observed.

RESULTSPartial remission of the hepatic lesions was achieved in 13 (56.5%) of the patients following the treatment, and the condition was stabilized in 5 patients (21.7%). No severe complications were observed in these patients.

CONCLUSIONPercutaneous chemotherapy pump placement for portal vein chemotherapy can be safe and effective for management of hepatic metastasis of colorectal cancer.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Colorectal Neoplasms ; pathology ; Female ; Humans ; Infusion Pumps, Implantable ; Infusions, Intravenous ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Portal Vein

OBJECTIVE: To explore the prognostic factors of patients with unresectable liver metastasis colorectal cancer after failed conversion chemotherapy. METHODS: A retrospective, case-controlled study was performed. Study subjects were 105 patients who were diagnosed with synchronous liver metastasis colorectal cancer after failed chemotherapy (metastasis evaluated as unresectable after the conversion chemotherapy) at Xinhua Hospital, Shanghai Jiaotong University from January 2012 to December 2015. Overall survival(OS) was retrospectively analyzed using Kaplan-Meier method. Log-rank test was used to compare survival among groups. Univariate and multivariate analysis was conducted for prognosis using Cox regression model. RESULTS: Of 105 cases,70 were male and 35 were female with median age of 60 years old. Twenty-one patients had right colon cancer, 41 had left colon cancer, 42 had rectal cancer and 1 had synchronous cancers(sigmoid colon and rectum). One hundred and two (97.1%) patients were cT3-4 and 90 patients were cN+ (imaging diagnosis). Eighty-nine (84.8%) patients were loaded with 2 or more liver metastases with the median maximum diameter of 48.3 mm. The patients were followed up for 3 to 43 months from the day of diagnosis. The median OS was 11 months (interquartile range, 8-18). The median OS of patients with cN0, cN1 and cN2 stage was 17, 13 and 10 months, respectively(P=0.026). The median OS of patients with single lesion, 2-3 lesions, 4-10 lesions and more than 10 lesions was 15, 15, 17 and 9 months, respectively (P=0.002). OS of patients with maximum diameter of liver metastatic lesion ≤ 50 mm, 51-100 mm and >100 mm was 15, 10 and 8 months, respectively(P=0.003). The median OS of patients with chemotherapy response of partial response (PR), stable disease (SD) and progressive disease (PD) was 17, 14 and 8 months, respectively(P<0.001). OS was 17 months in patients receiving second line chemotherapy and was 10 months in those without second line chemotherapy (P<0.001). OS in patients undergoing primary tumor resection was 13 month and in those without primary tumor resection was 9 months; the difference was not significant (P=0.060). Multivariate analysis showed that cN2(HR=2.115, 95%CI:1.089-4.109, P=0.027), the maximum diameter of liver metastatic lesion more than 100 mm (HR=3.112, 95%CI:1.455-6.657, P=0.003), chemotherapy response of PD (HR=4.435, 95%CI:2.506-7.533,P<0.001) and without second line chemotherapy(HR=4.432,95%CI:2.186-8.986, P=0.010) were independent prognostic factors. CONCLUSIONS For patients with unresectable liver metastasis from colorectal cancer after failed conversion chemotherapy, prognostic factors include cN2, the maximum diameter of liver metastatic lesion, chemotherapy response and second line chemotherapy. Whether the resection of primary tumor can prolong OS further study.
Antineoplastic Agents ; therapeutic use ; China ; Colorectal Neoplasms ; drug therapy ; pathology ; Female ; Humans ; Liver Neoplasms ; diagnosis ; secondary ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Treatment Failure

Abnormal glycosylation due to dysregulated glycosyltransferases and glycosidases is a key phenomenon of many malignancies, including colorectal cancer (CRC). In particular, increased ST6 Gal I (beta-galactoside alpha 2, 6 sialyltransferase) and subsequently elevated levels of cell-surface alpha 2, 6-linked sialic acids have been associated with metastasis and therapeutic failure in CRC. As many CRC patients experience metastasis to the liver or lung and fail to respond to curative therapies, intensive research efforts have sought to identify the molecular changes underlying CRC metastasis. ST6 Gal I has been shown to facilitate CRC metastasis, and we believe that additional investigations into the involvement of ST6 Gal I in CRC could facilitate the development of new diagnostic and therapeutic targets. This review summarizes how ST6 Gal I has been implicated in the altered expression of sialylated glycoproteins, which have been linked to CRC metastasis, radioresistance, and chemoresistance.
Antigens, CD/*metabolism ; Colorectal Neoplasms/*metabolism/pathology/*therapy ; Drug Resistance, Neoplasm ; Glycoproteins/*metabolism ; Humans ; Liver Neoplasms/secondary ; Lung Neoplasms/secondary ; Radiation Tolerance ; Receptor, Epidermal Growth Factor/metabolism ; Sialic Acids/*metabolism ; Sialyltransferases/*metabolism

OBJECTIVETo evaluate the value of infusion chemotherapy by pump implantation via hepatic artery or portal vein or both (double-pump chemotherapy, DPC) for hepatic metastasis from colorectal cancer.

METHODSThirty patients with hepatic metastasis from colorectal cancer were divided into three groups: 1. Group I-DPC (12 patients). 2. Group II-hepatic artery implantation chemotherapy (10 patients) and 3. Group III-portal vein implantation chemotherapy (8 patients).

RESULTSResponse rate was 66.7% in group I, 60% in group II and 37.5% in group III. The 0.5-, 1-, 2-year survival rates were 100.0%, 75.0%, 41.7% in group I, 90.0%, 60.0%, 30.0% in group II and 87.5%, 50.0%, 25.0% in group III.

CONCLUSIONDouble pump implantation chemotherapy is effective in treating hepatic metastasis from colorectal cancer. It is better than hepatic artery or portal vein pump-implantation chemotherapy alone.

Adult ; Aged ; Colorectal Neoplasms ; drug therapy ; pathology ; Drug Therapy ; methods ; Female ; Hepatic Artery ; Humans ; Infusion Pumps, Implantable ; Infusions, Intra-Arterial ; Infusions, Intravenous ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Portal Vein ; Therapeutics

OBJECTIVETo explore the inhibitory effect of combined administration of bear bile powder (BBP) and cyclophosphamide (Cytoxan, CTX) on colorectal cancer liver metastasis by regulating tumor promotion inflammation microenvironment.

METHODThe CRC liver metastasis mode in mice was established through in situ spleenic injection of SL4 tumor cells into spleens. The mice were randomly divided into 5 groups: the model group, the CTX (80 mg x kg(-1)) treatment group, the CTX + BBP high dose (300 mg x kg(-1)) group, the CTX + BBP middle dose (150 mg x kg(-1)) group and the CTX + BBP low dose (75 mg x kg(-1)) group. Mice were orally administered with drugs for 12 days, and sacrificed on the 13'h day for weighing their spleens and lives, HE staining, and immunofluorescence analysis. Their peripheral blood, and metastatic tumor in spleens and lives were analyzed with flow cytometry.

RESULTSpleen and liver weights of the: CTX treatment group and other doses groups were significantly lower than that of the model group. HE staining and immunofluorescence analysis showed that lymphocyte infiltration was detected in normal tissues, and macrophages infiltration was observed around the tumor tissues. Flow cytometry analysis showed that the number of T-lymphocytes in peripheral blood of different doses groups were much higher than that of the CTX treatment group (P < 0.05), with the rise in the ratio of CD4/CD8; the total number of lymphocytes in spleen cell suspension increased in different doses groups, compared to the CTX treatment group, with notable increase in B cells (P < 0.05) and significant decrease in CD11b, F4/80 cells (P < 0.05). The combined treatment showed less monocyte macrophages in liver metastasis than that of the CTX treatment group.

CONCLUSIONThe combined treatment of bear bile powder and cyclophosphamide has the effect in not only protecting liver and increase immunity, but also in anti-inflammation and antitumor by regulating tumor microenvironment and reducing the collection of mononuclear macrophages. Particularly, the combined administration of low dose of bear bile powder and CTX shows the most significant effect in reducing inflammatory cell infiltration.

Animals ; Bile ; chemistry ; Colorectal Neoplasms ; drug therapy ; mortality ; pathology ; Combined Modality Therapy ; Cyclophosphamide ; administration & dosage ; Humans ; Liver Neoplasms ; drug therapy ; mortality ; physiopathology ; secondary ; Male ; Mice ; Mice, Inbred C57BL ; Tumor Microenvironment ; drug effects ; Ursidae