OBJECTIVETo evaluate the application of multidisciplinary treatment (MDT) in patients with liver metastasis of colorectal cancer(CLM).

METHODSClinical data of 118 patients with liver metastasis of colorectal cancer, including 32 patients with MDT (MDT group) and 86 patients without MDT (control group), from February 2014 to April 2015 in PLA General Hospital were analyzed retrospectively. Compliance of preoperative examination and adjuvant therapy, and efficacy-associated indexes were compared between the two groups.

RESULTS(1) As compared to control group, statistically significant increase in imaging examination ratio was found in MDT group: chest CT [87.5%(28/32) vs. 40.7%(35/86), P=0.0000], abdominal MRI [84.4%(27/32) vs.61.6%(53/86), P=0.019], pelvic MRI [63.7%(7/11) vs. 24.3%(8/33), P=0.017]. The preoperative assessment of TNM staging was also higher in MDT group [100%(32/32) vs. 20.9%(18/86), P=0.0000], while there was no significant difference in accuracy rate of TNM staging between the two groups [81.3%(26/32) vs. 66.7%(12/18), P=0.2465]. (2) Rates of preoperative chemotherapy and chemotherapy completion were also higher in MDT group than those in control group [90.6%(29/32) vs. 62.8%(54/86), P=0.0033; 82.8% (24/29) vs. 57.4% (31/54), P=0.000], but conversion rate of unresectable CLM showed no significant difference [24.0% (6/25) vs. 14.3% (7/49), P=0.299 ]. (3) Rate of one-stage resection or ablation was higher in MDT group compared to control group [76.9%(10/13) vs. 36.0%(9/25), P=0.038], and resection rate of metastasis nidus was also higher in MDT group [77.0%(20/26) vs. 44.9%(13/29), P=0.015]. No significant differences were observed in rates of R0 resection, positive surgical margin, lymph node clearance, ablation of metastasis nidus, pathological complete response, postoperative chemotherapy or postoperative complications (all P>0.05).

CONCLUSIONMDT has the advantages on standardization of preoperative examination and perioperative chemotherapy, and can improve the rate of one-stage resection or ablation, as well as resection of metastasis nidus.

Aged ; Colorectal Neoplasms ; pathology ; Combined Modality Therapy ; Female ; Hepatectomy ; Humans ; Liver Neoplasms ; secondary ; therapy ; Lymph Nodes ; Male ; Middle Aged ; Neoplasm Staging ; Postoperative Complications ; Retrospective Studies ; Tomography, X-Ray Computed ; Treatment Outcome

Granulocyte colony-stimulating factor (G-CSF) is an essential regulator of neutrophil trafficking and is highly expressed in multiple tumors. Myeloid derived suppressor cells (MDSCs) promote neoplastic progression through multiple mechanisms by immune suppression. Despite the findings of G-CSF function in colon cancer progression, the precise mechanism of G-CSF on MDSCs regulation and its blockade effects on tumor growth remains a worthy area of investigation. In this study we observed an overexpression of G-CSF in a mouse colitis-associated cancer (CAC) model, which was consistent with the accumulation of MDSCs in mouse colon tissues. Further in vitro studies demonstrated that G-CSF could promote MDSCs survival and activation through signal transducer and activator of transcription 3 (STAT3) signaling pathway. Moreover, compared with isotype control, anti-G-CSF mAb treatment demonstrated reduced MDSC accumulation, which led to a marked decrease in neoplasm size and number in mice. Our results indicated that G-CSF is a critical regulating molecule in the migration, proliferation and function maintenance of MDSCs, which could be a potential therapeutic target for colitis-associated cancer.
Animals ; Carcinogenesis ; Colitis ; complications ; Colorectal Neoplasms ; complications ; drug therapy ; immunology ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Granulocyte Colony-Stimulating Factor ; genetics ; metabolism ; Immunotherapy ; Mice ; Molecular Targeted Therapy ; Myeloid Cells ; immunology ; metabolism ; pathology

BACKGROUND/AIMS: Colorectal adenomas that are > or =10 mm have villous histology or high-grade dysplasia, or that are associated with > or =3 adenomas are considered high-risk for metachronous advanced neoplasia. We evaluated the cumulative incidence of metachronous advanced neoplasia according to the total number of high-risk findings detected on baseline colonoscopy. METHODS: This was a retrospective cohort study performed in 862 patients who underwent removal of colorectal adenomas between 2005 and 2009. At least one surveillance colonoscopy had been conducted at Konkuk University Medical Center, Seoul, Korea. RESULTS: The cumulative incidence of metachronous advanced neoplasia in patients with 0, 1, 2, and 3-4 high-risk findings at 1 year were 0.7%, 1.3%, 2.8%, and 8.0%; at 3 years, those were 5.9%, 11.9%, 15.5%, and 24.7%; and at 5 years, those were 8.5%, 18.7%, 26.3%, and 37.2%, respectively. In a multivariate model, the risk of metachronous advanced neoplasia was significantly higher for the multiple high-risk findings group when compared with the 0 high-risk findings group (1 high-risk (+): hazard ratio, 1.86 [95% confidence interval, 1.00-3.44]; 2 high-risk (+): 1.84 [0.88-3.84]; and 3-4 high-risk (+): 3.29 [1.54-7.01]; ptrend=0.020). CONCLUSIONS: The presence of overlapping multiple high-risk findings was associated with an increased risk of advanced neoplasia during surveillance.
Adenoma/epidemiology/*etiology/pathology ; Aged ; Colonic Polyps/complications/surgery ; *Colonoscopy ; Colorectal Neoplasms/epidemiology/*etiology/pathology ; Early Detection of Cancer/methods ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasms, Second Primary/epidemiology/*etiology/pathology ; Population Surveillance/methods ; Proportional Hazards Models ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Time Factors ; Tumor Burden

Ulcerative colitis is an idiopathic chronic inflammatory bowel disease and its incidence in Korea has rapidly increased over the past two decades. Since ulcerative colitis is associated with increased risk for colorectal cancer, annual or biannual colonoscopy with four quadrant random biopsies at every 10 cm segments has been recommended for surveillance of colitic cancer in patients with long standing left-sided or extensive colitis. Recent epidemiologic data and meta-analysis suggest that the increment of colorectal cancer risk in ulcerative colitis was not larger than that of previous studies. Moreover, in addition to the extent and duration of colitis, other risk factors such as family history of colorectal cancer, primary sclerosing cholangitis, stricture, pseudopolyps, and histologic severity of inflammation have been recognized. As a result, updated guidelines provide surveillance strategies adjusted to the individual patient's risk for colitic cancer. Regarding surveillance method, target biopsy under panchromoendoscopy is preferentially recommended rather than random biopsy.
Cholangitis, Sclerosing/complications ; Colitis, Ulcerative/*complications ; Colon/pathology ; Colorectal Neoplasms/epidemiology/*etiology ; Humans ; Inflammatory Bowel Diseases/complications ; Polyps ; Risk Factors

OBJECTIVETo compare the short- and long-term outcomes of patients with synchronous colorectal liver metastases receiving either simultaneous or staged hepatectomy.

METHODSClinical and follow-up data of 64 patients with synchronous colorectal liver metastasis who underwent either simultaneous or staged hepatectomy between January 2003 and December 2011 in our hospital were reviewed retrospectively. Among them 20 patients underwent simultaneous resection of colorectal cancer and liver metastasis(simultaneous group) and 44 patients underwent staged operations(staged group).

RESULTSThe Clavien-Dindo grade 1, 2, 3 complication rates in simultaneous group were 10.0%, 15.0% and 15.0% respectively, and were staged group 13.6%, 13.6% and 22.7% respectively in staged group, and the difference was not statistically significant(P>0.05). The 1-, 2- and 3-year overall survival rates in simultaneous group were 85.0%, 59.6% and 37.2% respectively, compared with 90.9%, 68.2% and 47.1% in staged group, and the difference was not statistically significant(P>0.05). The median disease-free survival time in simultaneous group was 6 months versus 7 months in the staged group, which was comparable(P>0.05). Multivariate analysis revealed that positive primary lymph-node(P=0.020), prehepatectomy CEA>20 μg/L(P=0.017) were independent risk factors of overall survival, and having the opportunity to receive local radical therapy combined with chemotherapy after recurrence was a protective factor(P=0.001), while the timing of resection (simultaneous or staged strategy) did not reach statistical significance according to overall survival(P>0.05).

CONCLUSIONSFor synchronous colorectal liver metastasis there are no significant differences in postoperative complication rate and long-term survival between curative simultaneous and staged resection.

Colorectal Neoplasms ; pathology ; Disease-Free Survival ; Hepatectomy ; Humans ; Liver Neoplasms ; secondary ; surgery ; Neoplasm Recurrence, Local ; Postoperative Complications ; Retrospective Studies ; Survival Rate

OBJECTIVETo confirm that the severity of inflammation can promote the colitis-associated colorectal cancer(CAC) and explore the function of STAT3 signal pathway in CAC.

METHODSMutagenic agent azoxymethane(AOM) and pro-inflammatory agent dextran sodium sulfate salt (DSS) were used to develop a mouse model of CAC. By changing the concentration of DSS (0, 1% and 2% respectively), the mouse model with different extent of severity of inflammation was developed and the risk of carcinogenesis among these groups was compared. The expression of STAT3 signal pathway was detected by immunohistochemistry staining.

RESULTSIn the evaluation of inflammatory severity, disease activity index, histopathological inflammation scores and the expression of pro-inflammation chemokines such as TNF-α, IL-6 and IL-12 in the higher inflammatory response group were higher than that in the lower inflammatory response group. The incidence of colorectal tumor was 100%(12/12) in the higher inflammatory response group and the incidence of colorectal tumor was 58.3%(7/12) in the lower inflammatory response group, and the difference between these two group was statistically significant (P<0.05). The multiplicity(number of tumors/colon) was 12.5±0.5 in the higher inflammatory response group and the multiplicity was 6.6±1.0 in the lower inflammatory response group, and the difference between these two groups was statistically significant (P<0.001). The tumor load(sum of tumor diameters per mouse) in the higher inflammatory response group was 44.2±2.4 mm and that in the lower inflammatory response group was only 18.7±2.7 mm, and the difference between these two groups was statistically significant (P<0.0001). Moreover, the expression of p-STAT3 (Tyr705) was higher in colitis tissue of the higher inflammatory response group than that of the lower inflammatory response group.

CONCLUSIONSInflammation can promote the colitis-associated CAC. And the activation of STAT3 signal pathway may promote the development of CAC.

Animals ; Azoxymethane ; Colitis ; complications ; Colonic Neoplasms ; Colorectal Neoplasms ; etiology ; pathology ; Dextran Sulfate ; Disease Models, Animal ; Immunohistochemistry ; Inflammation ; Interleukin-6 ; Mice ; Mice, Inbred C57BL ; STAT3 Transcription Factor ; Signal Transduction ; Tumor Necrosis Factor-alpha

OBJECTIVEthe aim of this study was to determine the clinicopathological characteristics of colorectal cancer (CRC) patients complicated with type 2 diabetes mellitus (T2DM ).

METHODSA total of 3, 202 patients with CRC confirmed pathologically in Tianjin Union Medicine Center from January 2005 to December 2009 were included in this study. We analyzed the differences in clinicopathological features between T2DM patients and non-diabetic patients according to age of diagnosis, gender, tumor site, stage, gross type, histological type, and differentiation.

RESULTSFrom 2005 to 2009, the number of CRC patients increased yearly. The high incidence age of all CRC patients was 51 to 80 years old. The male to female ratio was 1.18:1, showing that the number of female patients with CRC was increased significantly compared with males. The CRC distribution of T2DM patients and non-diabetic patients showed a predominance of rectal cancer (64.4%, 68.7%), followed by sigmoid colon cancer (12.5%, 13.0%), and moderately differentiated ulcer-type adenocarcinoma. Compared with non-diabetic patients, T2DM patients were older (66.2 years versus 62.7 years, P < 0.001) and had more multiple CRCs (3.5% versus 1.6%, P < 0.001). Moreover, the proportion of lymph node or organ metastasis in T2DM patients was higher than that in non-diabetic patients (52.6% versus 45.6%, P < 0.05). No significant differences were observed between both groups in terms of gender, gross type, histological type, and differentiation(P > 0.05 for all).

CONCLUSIONSCRC incidence shows an increasing trend with age. CRC patients with T2DM have an older age of onset, higher proportion of lymph node and distant organ metastasis than in non-diabetic patients.

Adenocarcinoma ; complications ; pathology ; Aged ; Colorectal Neoplasms ; complications ; pathology ; Diabetes Mellitus, Type 2 ; Female ; Humans ; Male ; Middle Aged

PURPOSE: We investigated the effects of proteinuria and renal insufficiency on all-cause mortality in patients with colorectal cancer, with special emphasis on cancer staging and cancer-related deaths. MATERIALS AND METHODS: We retrospectively studied a cohort of patients with colorectal cancer. In protocol 1, patients were classified into four groups based on the operability of cancer and proteinuria: group 1, early-stage cancer patients (colorectal cancer stage < or =3) without proteinuria; group 2, early-stage cancer patients with proteinuria; group 3, advanced-stage cancer patients without proteinuria (colorectal cancer stage=4); and group 4, advanced-stage cancer patients with proteinuria. In protocol 2, patients were classified into four similar groups based on cancer staging and renal insufficiency (eGFR <60 mL/min/1.73 m2). Between January 1, 1998 and December 31, 2009, 3379 patients were enrolled in this cohort and followed until May 1, 2012 or until death. RESULTS: The number of patients with proteinuria was 495 (14.6%). The prevalence of proteinuria was higher in advanced-stage cancer (n=151, 22.3%) than in early-stage cancer patients (n=344, 12.7%). After adjusting for age, gender and other clinical variables, the proteinuric, early-stage cancer group was shown to be associated with an adjusted hazard ratio of 1.67 and a 95% confidence interval of 1.38-2.01, compared with non-proteinuric early-stage cancer patients. However, renal insufficiency was not associated with colorectal cancer mortality. CONCLUSION: Proteinuria is an important risk factor for cancer mortality, especially in relatively early colorectal cancer.
Aged ; Colorectal Neoplasms/complications/*mortality/pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Prevalence ; Proteinuria/*complications/epidemiology ; Renal Insufficiency/complications ; Retrospective Studies ; Risk Factors

BACKGROUND/AIMS: The purpose of this study was to investigate the clinicopathologic features of double primary cancers of the stomach and colorectum, compared to colorectal cancer alone. METHODS: A retrospective analysis was made of 5,288 patients who underwent colorectal cancer surgery between January 2000 and December 2009 at Severance Hospital of Yonsei University. The clinicopathologic features were analyzed between 63 patients of double primary cancers and case-matched 126 patients of colorectal cancer alone. We classified double primary cancers into subgroups as premetachronous, synchronous and postmetachronous gastric cancer to identify differences between the three subgroups also. RESULTS: Double primary cancers group showed 4.3 year-older age, lower BMI, and higher percentage of peritoneal metastasis, compared to colorectal cancer alone group. Overall and colorectal cancer specific survival did not have any significant difference between two groups. In histologic type of gastric cancer, a high percentage of undifferentiated adenocarcinoma (55.6%) and signet ring cell carcinoma (30.2%) were noted. CONCLUSIONS: Double primary cancers of the stomach and colorectum had older-age onset, lower BMI and higher metastasis to peritoneum than colorectal cancer alone. Combined gastric cancer consisted of high percentage of undifferentiated and signet ring cell carcinomas.
Adenocarcinoma/pathology ; Age Factors ; Aged ; Body Mass Index ; Carcinoma, Signet Ring Cell/pathology ; Colorectal Neoplasms/complications/*pathology ; Female ; Humans ; Male ; Middle Aged ; Odds Ratio ; Peritoneal Neoplasms/secondary ; Polyps/pathology ; Retrospective Studies ; Stomach Neoplasms/complications/*pathology

OBJECTIVETo investigate the independent predictors of postoperative mortality, morbidity, and long-term survival in patients with stage IV ( colorectal cancer.

METHODSClinical data of 189 patients with stage IV( colorectal cancer undergoing palliative resection of primary tumor in the presence of unresectable synchronous metastases were analyzed retrospectively.

RESULTSEighty-six (45.5%)patients developed postoperative complications. Preoperative predictors of medical complications included age(≥65, P=0.039) and emergency operations (P=0.001). Preoperative predictors of surgical complications included advanced local disease (T4, P=0.022) and lymph node spread (N2, P=0.009). Seventeen (9.0%) patients died in the postoperative period. Mortality was independently associated with age(P=0.013), peritoneal dissemination(P=0.010), emergency operations(P=0.001) and medical complications(P=0.008). The survival rates at 1-, 2-, and 3- year of 172 patients admitted in survival analysis were 41.2%, 22.7% and 7.7% respectively. Independent factors associated with poor overall survival included lymph node spread(N2, P=0.015) and poor tumor differentiation(P=0.038).

CONCLUSIONSEmergency operations should be avoid when palliative resection of primary tumor is considered for stage IV( colorectal cancer patients, especially for elderly patients and those with peritoneal dissemination. The significance of palliative resection is limited for stage IV ( colorectal cancer patients with lymph node spread and poor tumor differentiation.

Aged ; Colorectal Neoplasms ; pathology ; surgery ; Humans ; Lymph Nodes ; Neoplasm Staging ; Palliative Care ; Postoperative Complications ; Prognosis ; Retrospective Studies ; Survival Analysis