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

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

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

BACKGROUND/AIMS: Colorectal neuroendocrine carcinoma is a rare neoplasm exhibiting fulminant progression and having poor prognosis. The purpose of this study is to verify the clinicopathologic characteristics of colorectal neuroendocrine carcinoma. METHODS: From June 1997 to December 2004 at Asan Medical Center, ten patients were originally identified as colorectal neuroendocrine carcinoma on the basis of H&E and immunohistochemical staining (IHC). Carcinoid tumors were excluded in this study. Medical records of thirteen patients were reviewed retrospectively. RESULTS: Ten patients (0.2%) with colorectal neuroendocrine tumors were identified from 4,512 patients with colorectal cancer; ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation. Their median age was 60 (41-83) years. The subjects consisted of six males and seven females. Nine tumors were located in the rectum, two in the sigmoid, and each one in the transverse colon and cecum, respectively. Nine of ten neuroendocrine carcinomas expressed synaptophysin, but chromogranin A were expressed in four. All patients were advanced at the time of diagnosis, with AJCC TNM staging: stage IIIB (n=2), stage IIIC (n=3), and stage IV (n=8). The median survival for ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation were 16.4 months and 30 months, respectively. Five patients who received chemotherapy showed median survival of 32 months (stage III) and 17.5 months (stage IV), whereas other five patients without chemotherapy died with a median survival of 6.2 months. CONCLUSIONS: Colorectal neuroendocrine tumors are extremely rare showing aggressive behavior biologically, i.e fulminant early distant metastasis. Nevertheless, improved survival may be achieved by aggressive multimodality therapy.
Adenocarcinoma/pathology ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Carcinoma, Neuroendocrine/drug therapy/mortality/*pathology ; Chromogranin A/analysis/immunology ; Colorectal Neoplasms/drug therapy/mortality/*pathology ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Retrospective Studies ; Sigmoid Neoplasms/drug therapy/mortality/pathology ; Synaptophysin/analysis/immunology ; Tumor Markers, Biological/analysis/immunology

BACKGROUND/AIMS: Limited options remain for patients with metastatic colorectal cancer (CRC) after failure of standard systemic chemotherapy. Readministration of chemotherapeutic agents by hepatic arterial infusion (HAI) has the rationale of providing higher concentrations of chemotherapeutic agents to hepatic metastases. The present study was conducted to evaluate the efficacy and safety of HAI of fluorouracil with leucovorin (HAI 5-FU/LV) for patients with liver metastases from CRC. METHODS: Fourteen patients with liver metastases from CRC who received HAI 5-FU/LV after failure of systemic chemotherapy containing fluorouracil and leucovorin were identified and their medical records were reviewed. RESULTS: Of 10 patients evaluable for response, one partial response, six stable disease, and three progressive disease were reported. Additionally, the overall response and disease control rates were 7% and 50%, respectively. The median time to progression was 4.3 months (range, 2.9 to 5.6), to hepatic progression was 5.8 months (range, 4.7 to 6.9), and to extrahepatic progression was 5.8 months (range, 2.3 to 9.2). No grade 3/4 hematologic toxicities occurred and one case of abdominal pain and two cases of oral mucositis were the only grade 3 nonhematologic toxicities. Catheter-related complications occurred in three patients: one thrombosis, one infection, and one displacement. CONCLUSIONS: HAI 5-FU/LV was well tolerated and showed modest efficacy for patients with liver metastases from refractory CRC. Readministration of previously used chemotherapeutic agents via the hepatic artery could be an effective salvage option and warrants further investigation in a prospective trial.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects ; Colorectal Neoplasms/*pathology ; Female ; Fluorouracil/administration & dosage/*therapeutic use ; Humans ; *Infusions, Intra-Arterial ; Leucovorin/administration & dosage/*therapeutic use ; Liver Neoplasms/*drug therapy/mortality/*secondary ; Male ; Middle Aged ; *Salvage Therapy

OBJECTIVETo study the effects of Chinese materia medica (CMM) combined chemotherapy on the recurrence, metastasis, and the disease free survival (DFS) of stage II and III colorectal cancer (CC) patients after radical cure.

METHODSRecruited were 366 inpatients and outpatients with stage II and III colorectal cancer (CC) from Changhai Hospital, Second Military Medical University, and Tumor Department of Longhua Hospital, Shanghai University of Traditional Chinese Medicine from January 2002 to December 2008. A non-randomized concurrent control method was adopted. Patients were assigned to the combination group (treated by CMM + chemotherapy, 189 cases) and the chemotherapy group (177 cases) according to whether they were willing to receive the CMM treatment for more than 6 successive months. By using follow-ups at clinics, by letter, and by telephone, the DFS, 1-, 2-, 3-, and 5-year DFS ratios were observed. The correlations between DFS and the gender, age, tumor location, staging of clinical pathology, pathological type, chemotherapeutic cycle, radiotherapy, CMM treatment, end point event (recurrence and metastasis) were analyzed.

RESULTSThe recurrence or metastasis occurred in 145 cases (39. 61%) of the 366 patients. Of them, local recurrence occurred in 17 cases (11.72%), liver metastasis in 45 cases (31.03%), lung metastasis in 52 cases (35.86%), and metastasis in other parts in 53 cases (36.55%). Results of one-factor analysis showed six factors such as the tumor location, pathological type, staging of clinical pathology, chemotherapeutic cycle, radiotherapy, and CMM treatment were correlated with the DFS, showing statistical difference (P<0.01, P<0.05). Results of multifactor analysis showed staging of clinical pathology, chemotherapeutic cycle, and CMM treatment were correlated with the DFS, showing statistical difference (P<0.01). Results of stratified study on the staging of clinical pathology indicated that the primary tumor location (P=0.016) and the pathological type (P=0.047) were the independent predictors for DFS of stage II CC. The median DFS of the two groups could not be calculated. Results of stratified study on the stages of clinical pathology indicated that CMM treatment (P=0.000) and chemotherapeutic cycle (P=0.017) were independent predictors for DFS of stage III CC. As for comparing the composition ratio of the two therapeutic cycles, results showed the baselines of the chemotherapeutic cycle of the two groups were balanced. Further comparison showed the median DFS for the chemotherapy group at stage III was 24. 16 months, while it could not be calculated in the combination group. The DFS, 1-, 2-, 3-, and 5-year DFS ratios were 92%, 72%, 61%, and 59%, respectively in the stage III CC combination group, while they were 74%, 50%, 36%, and 20%, respectively in the stage IlI CC chemotherapy group.

CONCLUSIONCMM combined chemotherapy could prolong the DFS of stage III CC patients after radical cure.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; mortality ; pathology ; Combined Modality Therapy ; Disease-Free Survival ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Phytotherapy

OBJECTIVETo evaluate the effect of Quxie Capsule (QXC) on the median survival time and quality of life in patients with advanced colorectal carcinoma.

METHODSForty patients with advanced colorectal carcinoma were observed in a randomized controlled clinical trial (RCT). Out of them the 37 evaluable patients were assigned into the treatment group (18 patients) and the control group (19 patients). They were all treated by the routine treatment for cancer, including chemotherapy and radiotherapy, while those in the treatment group were administered with QXC additionally. After being treated for 3 months, the follow-up study was carried out to evaluate the fatality rate (FR), survival time (ST), median survival time (mST), time to progression (TTP), and quality of life (QOF).

RESULTSFR, mST, ST and TTP in the treatment group were 11.1% (2/18), 17 months, 22.63 +/- 7.34 months, and 17.76 +/- 5.62 months respectively, and those in the control group were 42.1% (8/19), 13 months, 19.76 +/- 8.28 months and 12.68 +/- 9.26 months respectively, showing significant difference between the two groups (P < 0.05). The scores of TCM symptom, QOF and KPS in the treatment group were 15.59 +/- 3.78, 54.06 +/- 3.96 and 64.71 +/- 6.24 before treatment, and 10.53 +/- 5.57, 58.65 +/- 4.03, 69.41 +/- 4.29 after treatment, respectively, showing significant improvement (P < 0.05). While the three scores in the control group were 16.11 +/- 3.99, 54.06 +/- 4.39 and 64.44 +/- 5.11 before treatment, and 19.61 +/- 7.78, 50.17 +/- 8.26 and 60.00 +/- 9.70 after treatment, respectively, showing a statistically significant worsening tendency in the latter two (P <0.05).

CONCLUSIONQXC can reduce the FR, prolong the ST, mST, mCFPT, and improve the QOF in patients with advanced colorectal carcinoma.

Adenocarcinoma ; drug therapy ; mortality ; pathology ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Capsules ; Colorectal Neoplasms ; drug therapy ; mortality ; pathology ; Combined Modality Therapy ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy ; Quality of Life ; Survival Analysis ; Survival Rate

OBJECTIVETo explore the efficacy and safety of CPT-11 combined with fluoropyrimidine in treatment for advanced or metastatic colorectal carcinoma.

METHODSFrom January 2001 to September 2003, 43 patients with advanced or metastatic colorectal carcinoma were randomized into two groups, group A [CPT-11 90 - 25 mg/m(2) continuous infusion for 10 h and folinic acid (FA) 30 mg x m(-2) x d(-1) + 5-FU 425 mg x m(-2) x d(-1) x 2 d continuous infusion for 48 h, every two weeks as a cycle in total of no less than six cycles] and group B (CPT-11 90 - 125 mg/m(2) continuous infusion for 10 h every two weeks as a cycle in total of no less than six cycles and capecitabine 1250 mg x m(-2) x d(-1) by oral divided into two doses, continuously taken without interruption for three months).

RESULTSIn this study, overall response rate (ORR) was 44.2%, disease control achieved in 83.7%, Time to progression (TTP) was 11.0 months and overall survival (OS) was 14.6 months. Response rate in group A was 31.3% and 51.9% in group B. TTP of group A was 8.4 months and that of group B was 12.5 months; OS in group A was 14.2 months and 17.9 months in group B. In 43 cases with 502 cycles of chemotherapy, grade III side effect occurred only in 3.0% and no therapy-related death occurred. Nausea and vomiting was the most common side effect with an occurrence rate of 31.9% in group A and 2 cases of grade III, and 22.7% in group B with no case of grade III. Occurrence of side effect was much lower in group B than that of group A except hand-foot syndrome, which was 16.1% in group B with 2 cases of grade III as compared to 1.4% in group A with no case of grade III.

CONCLUSIONSCombination of CPT-11 and fluoropyrimidine is effective and safe in treatment for advanced/metastatic colorectal carcinoma. CPT-11 combined with capecitabine are not only more effective, but also its occurrence of side effect is lowered, and are especially high effective for lung metastasis. There is reasonable to recommend that combination of CPT-11 with capecitabine may be as first choice in treatment for such cases.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; analogs & derivatives ; Capecitabine ; Colorectal Neoplasms ; drug therapy ; mortality ; pathology ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Drug Administration Schedule ; Female ; Fluorouracil ; administration & dosage ; analogs & derivatives ; Humans ; Infusions, Intravenous ; Leucovorin ; administration & dosage ; Lung Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Survival Rate

BACKGROUNDHepatic arterial infusion chemotherapy for liver metastases is under evaluation because of the high target dose and low general toxicity. To investigate the efficacy and safety of a Folfox4 regimen administered through a combined hepatic arterial and systemic infusion for the first-line treatment of colorectal cancer (CRC) with unresectable liver metastases.

METHODSTwenty-seven CRC patients with unresectable hepatic metastases and no prior chemotherapy were enrolled into the study. They received a Folfox4 regimen; 1st day: HAI of oxaliplatin 85 mg/m(2) and L-folinic acid 200 mg/m(2), followed by a bolus hepatic arterial injection of 5-fluorouracil 400 mg/m(2), then continuous HAI of 5-FU 600 mg/m(2); 2nd day: infusion of L-folinic acid 200 mg/m(2) i.v. followed by an intravenous bolus injection of 5-Fluorouracil 400 mg/m(2), then continuous infusion of 5-fluorouracil 600 mg/m(2) i.v. The patients received HAI during the odd cycles, and the intravenous administration of the same Folfox4 regimen during the even cycles.

RESULTSA total of 236 treatment cycles were given with a median of 10 cycles. The therapy generated the following results after six treatment cycles: complete response (CR) 1/27 (3.7%), partial response (PR) 17/27 (63.0%), stable disease (SD) 6/27 (22.2%), and progress disease (PD) 3/27 (11.1%). Five patients had hepatectomy. The serum levels of both carcinoembryonic antigen (CEA) and CA19-9 were significantly reduced (P < 0.05). A median time to progression of 11 months and a median overall survival of 24 months were documented. The major adverse events included grade 1/2 nausea/vomiting, upper abdominal pain, peripheral neuropathy, and neutropenia/thrombocytopenia.

CONCLUSIONSThe Folfox4 regimen administered through combined hepatic arterial and systemic infusions is efficacious and safe for the treatment of CRC with unresectable liver metastases, and it facilitates the control of local lesions.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Colorectal Neoplasms ; drug therapy ; mortality ; pathology ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; Hepatic Artery ; Humans ; Infusions, Intra-Arterial ; Leucovorin ; administration & dosage ; adverse effects ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Organoplatinum Compounds ; administration & dosage ; adverse effects

OBJECTIVE: To prospectively evaluate the performance of computed tomography perfusion imaging (CTPI) in predicting the early response to transarterial chemo-lipiodol infusion (TACLI) and survival of patients with colorectal cancer liver metastases (CRLM). MATERIALS AND METHODS: Computed tomography perfusion imaging was performed before and 1 month after TACLI in 61 consecutive patients. Therapeutic response was evaluated on CT scans 1 month and 4 months after TACLI; the patients were classified as responders and non-responders based on 4-month CT scans after TACLI. The percentage change of CTPI parameters of target lesions were compared between responders and non-responders at 1 month after TACLI. The optimal parameter and cutoff value were determined. The patients were divided into 2 subgroups according to the cutoff value. The log-rank test was used to compare the survival rates of the 2 subgroups. RESULTS: Four-month images were obtained from 58 patients, of which 39.7% were responders and 60.3% were non-responders. The percentage change in hepatic arterial perfusion (HAP) 1 month after TACLI was the optimal predicting parameter (p = 0.003). The best cut-off value was -21.5% and patients who exhibited a > or = 21.5% decrease in HAP had a significantly higher overall survival rate than those who exhibited a < 21.5% decrease (p < 0.001). CONCLUSION: Computed tomography perfusion imaging can predict the early response to TACLI and survival of patients with CRLM. The percentage change in HAP after TACLI with a cutoff value of -21.5% is the optimal predictor.
Adult ; Aged ; Colorectal Neoplasms/mortality/*pathology ; Contrast Media/administration & dosage ; Ethiodized Oil/*administration & dosage ; Female ; Hepatic Artery/radiography ; Humans ; Liver Neoplasms/*drug therapy/mortality/*radiography/secondary ; Male ; Middle Aged ; Perfusion Imaging/*methods ; Prospective Studies ; Survival Rate ; Tomography, X-Ray Computed/methods