Colon cancer may invade the adjacent organ in the absence of distant metastasis, which is called stage T4bM0 colon cancer according to the 7th edition of TNM staging system. It is not rare in clinical setting, and usually recognized intraoperatively. How to deal with this situation is a big challenge for the surgeons. It is difficult to distinguish between dense adhesion and cancerous invasion. Intraoperative biopsy should be avoided because of the risk of tumor cell dissemination and frozen often gives false-negative results. After evaluating the resectability of the tumor sufficiently, the surgeon should make every effort to do an en bloc multivisceral resection and to achieve a margin-free (R0) resection if there is no absolute contraindication. This effort will bring long-term prognosis benefit for the patients with stage cT4bM0 colon cancer.
Colonic Neoplasms ; surgery ; Humans ; Neoplasm Staging

BACKGROUNDTissue factor (TF) is overexpressed in many malignant tumours and is linked to the pathogenesis and prognosis of such malignancies. In vitro studies have proved that reduced expression of TF has inhibitory effect on the angiogenesis and cell proliferation of the malignant tumour. Therefore, TF suppression has been raised as a possible treatment for malignant tumours. Here we investigated the effect of celecoxib on TF expression induced by tumour necrosis factor alpha (TNFalpha) in PANC-1 cells and a possible molecular mechanism underlying the celecoxib effect.

METHODSVarious doses of celecoxib solution were added to standard cell numbers of PANC-1 cells mixed with equal dose of TNFalpha for 6 hours. The expression of tissue factor was detected quantitatively by Western blot, whilst the activation of nuclear factor kappaB was tested by electromobility shift assay.

RESULTSAs the doses of celecoxib increased, the tissue factor expression was decreased in PANC-1 cells and so was the activation of nuclear factor kappaB.

CONCLUSIONSCelecoxib can downregulate the expression of tissue factor induced by TNFalpha in PANC-1 cells. This antitumour effect of celecoxib can be explained indirectly via its suppressive role in activation of nuclear factor kappaB.

Celecoxib ; Cell Line, Tumor ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Gene Expression Regulation ; drug effects ; Humans ; NF-kappa B ; metabolism ; Pancreatic Neoplasms ; metabolism ; pathology ; Pyrazoles ; pharmacology ; Sulfonamides ; pharmacology ; Thromboplastin ; genetics ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors

OBJECTIVETo study the characters of chronic pancreatitis complicated by non-calculous obstructive jaundice, and discuss the methods for differentiation and treatment.

METHODTwenty cases selected from January 1985 to December 2004 were analysed in the fields of differentiation and treatment.

RESULTSAll cases didn't present with typical clinical presentations and radiological features. Jaundice was presented as the main complaint. Stricture of the intra-pancreatic common bile duct was the symbolic radiological feature. Pancreatic disseminated inflammation was verified pathologically in these cases. CT, ultrasound, EUS, ERCP, MRCP and antigen-marker of neoplasm failed to offer the data for differentiation. The diagnosis could only be determined by pathological exam. The obstructive jaundice could be solved by biliary-enteric anastomoses successfully.

CONCLUSIONSThe patients with sole complaint of obstructive jaundice account for 15% of all inpatients with chronic pancreatitis. There exists a direct relationship between the jaundice and the pancreatic inflammation. This disorder should be differentiated from total pancreatic carcinoma, but few differentiated material could be offered by preoperative studies. Pathological result derived from the tissue sample obtained within the exploration would be reliable for diagnosis. The bypass between biliary tract and intestine would be a safe and economical treatment method.

Adult ; Aged ; Anastomosis, Roux-en-Y ; Biopsy, Needle ; Cholangiopancreatography, Endoscopic Retrograde ; Choledochostomy ; methods ; Chronic Disease ; Endosonography ; Female ; Humans ; Jaundice, Obstructive ; diagnosis ; etiology ; surgery ; Male ; Middle Aged ; Pancreaticoduodenectomy ; Pancreatitis ; complications ; diagnosis ; surgery ; Retrospective Studies ; Tomography, X-Ray Computed

OBJECTIVETo study the combined effect of gestational age and birth weight on metabolites related to inherited metabolic diseases (IMD).

METHODSA total of 3 381 samples ruled out of IMD by follow-up were randomly selected from 38 931 newborns who participated in the neonatal IMD screening during 2014-2016. The 3 381 neonates were categorized into seven groups according to their gestational age and birth weight: extremely preterm appropriate-for-gestational age (AGA) group (n=12), preterm small-for-gestational age (SGA) group (n=18), preterm AGA group (n=219), preterm large-for-gestational age (LGA) group (n=18), full-term SGA group (n=206), full-term AGA group (n=2 677), and full-term LGA group (n=231). Heel blood samples were collected from each group on postnatal days 3-7 after adequate breastfeeding. Levels of 17 key IMD-related metabolic indices in dried blood spots were measured using tandem mass spectrometry. Spearman′s correlation analysis was used to investigate the relationships between 17 IMD-related metabolic indices and their influencing factors, while covariance analysis was used to compare the metabolic indices between these groups.

RESULTSAfter adjusting the influencing factors such as physiological and pathological status, compared with the full-term AGA group, the extremely preterm AGA, preterm SGA, and preterm AGA groups had significantly reduced levels of leucine\isoleucine\hydroxyproline and valine (P<0.05); the preterm AGA group had a significantly decreased ornithine level (P<0.05); the extremely preterm AGA and preterm AGA groups had a significantly reduced proline level (P<0.05). Besides, the phenylalanine level in the extremely preterm AGA and preterm AGA groups, the methionine level in the preterm SGA group, and the tyrosine level in the preterm AGA group all significantly increased (P<0.05). The increased levels of free carnitine, acetylcarnitine, and propionylcarnitine were found in the preterm SGA and preterm AGA groups. The oleylcarnitine level also significantly increased in the preterm SGA group (P<0.05). Most carnitine indices showed significant differences between the SGA group and the AGA/LGA group in both preterm and full-term infants (P<0.05).

CONCLUSIONSLow gestational age and low birth weight may result in abnormal results in IMD screening. Therefore, gestational age and birth weight should be considered to comprehensively judge the abnormal results in IMD screening.

Birth Weight ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Small for Gestational Age ; Male ; Metabolic Diseases ; metabolism

OBJECTIVETo study the principle and surgical managements for the patients with anatomic variants of hepatic artery in the procedure of pancreaticoduodenectomy (PD).

METHODSOne hundred and seventy-six patients who underwent PD between January 2000 and July 2007 were investigated retrospectively. Hepatic arterial variants were analyzed according to the intraoperative finding and CT imaging were reviewed postoperatively.

RESULTSHepatic arterial variants were found intraoperatively in 20 cases of all 176 patients. Accessory right heptic artery, replaced right heptic artery and common heptic artery arising from the superior mesenteric artery (SMA) were present in 9 (5.1%), 5 (2.8%), 4 (2.3%) cases respectively,and replaced right heptic artery coming from the gastroduodenal artery was present in 2 cases (2.9%). All the variants of hepatic arteries arising from the superior mesenteric artery could be observed in spiral CT imaging. Most of the variant arteries were dissected intact intraoperatively except 2 cases with accessory right heptic artery arising from SMA.

CONCLUSIONSPerforming CT scan preoperatively, especially CTA,is effective to diagnose these disorders. Skillful surgical techniques can manage the anatomic variants safely.

Female ; Hepatic Artery ; abnormalities ; diagnostic imaging ; surgery ; Humans ; Male ; Middle Aged ; Pancreaticoduodenectomy ; Radiography ; Retrospective Studies

OBJECTIVETo investigate the effects of Hic-5/ARA55 on the growth of the human colorectal cancer cells (Lovo cells) and its mechanism.

METHODFlow cytometry (FCM) was used to study the cell cycle of Lovo cells (Lovo group), Lovo cells stably transfected with empty vector (Lovo-Vector group) and the Lovo cells stably transfected with vector containing Hic-5/ARA55 (Lovo-Hic-5/ARA55 group). Western blot assay was used to detect the principal cyclins in the three groups, and Luciferase assay was used to study the mechanism between Hic-5/ARA55 and the only target cyclin. The cells from the three groups were inoculated subcutaneously into 7 nude mice (Balb/c nu/nu) respectively to observe the effects of Hic-5/ARA55 on the growth of the cells in vivo. Seven weeks later, the subcutaneous tumors were harvested and weighed. Then immunohistochemistry assay was used to detect Hic-5/ARA55 and the target cyclin in the tumors.

RESULTSThe cell cycle was obviously delayed from G0/G1 to S stage in Lovo-Hic-5/ARA55 cells. A significantly higher expression of P27 was found in Lovo-Hic-5/ARA55 cells than in the other two groups. The weight of the subcutaneous tumors of Lovo-Hic-5/ARA55 cells, Lovo cells and Lovo-Vector cells were (0.33 +/- 0.23) g, (1.20 +/- 0.39) g and (1.30 +/- 0.49) g, respectively; the tumors of Lovo-Hic-5/ARA55 cells was significantly lighter than those of the other two groups (P<0.05). Hic-5/ARA55 and P27 were both over-expressed in implanted tumors of Lovo-Hic-5/ARA55 cells, while were both expressed lower or not expressed in the other two groups. And the expressions of Hic-5/ARA55 and P27 were highly positive correlated (r=0.816, P<0.05).

CONCLUSIONHic-5/ARA55 could inhibit the growth of Lovo cells both in vitro and in vivo by up-regulating the transcription of P27.

Animals ; Cell Cycle ; Cell Line, Tumor ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; Cyclin-Dependent Kinase Inhibitor p27 ; metabolism ; Gene Expression Regulation, Neoplastic ; Genetic Vectors ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Male ; Mice ; Mice, Nude ; Plasmids ; genetics ; RNA, Messenger ; genetics ; Transfection ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate the expression of proline-rich tyrosine kinase-2 (Pyk2) in human primary colorectal carcinoma (CRC) and it's prognostic significance.

METHODSThe expression of Pyk2 was retrospectively examined with immunohistochemistry (IHC) in 108 tissues of primary CRC. The correlation of Pyk2 expression to prognosis and relevant clinical factors were analyzed.

RESULTSThe rate of Pyk2 low-expression in CRC was 56.5% (61/108). The expression of Pyk2 correlated significantly to the histological grade (P < 0.05) and the TNM stage (P < 0.05), while no correlation between Pyk2 expression and age, tumor size (P > 0.05). Patients with Pyk2 over-expression had significantly higher 5-year survival rate (66.0%) than those with Pyk2 low-expression (31.4%). Pyk2 expression, together with carcinoma histologic grade and TNM stage were prognostic factors to CRC on the multivariate analysis.

CONCLUSIONSPyk2 expression can be a prognostic factor to the CRC patients together with other predictors.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; enzymology ; pathology ; Female ; Focal Adhesion Kinase 2 ; metabolism ; Humans ; Male ; Middle Aged ; Prognosis

Objective:To preliminarily verify the cross talk between tissue factor/active coagulation factor Ⅶ (TF/FⅦa) and epidermal growth factor receptor (EGFR) pathways in human colon cancer cells in culture.Methods:FⅦa was treated to HT-29 (KRAS-wild type) and LoVo (KRAS-mutant) colon cancer cells to activate TF/F Ⅶa pathway,qRT-PCR and Western blot were used to detect the expressions of amphiregulin (AREG) and epiregulin (EREG),ligands of EGFR on mRNA and protein levels,respectively.After knocking down expression of TF by TF-targeted siRNA transfection,FⅦa was treated and mRNA expressions of AREG and EREG were detected to see whether the FⅦa-induced effects were dependent on TF.Expressions of mRNA of TF and FⅦwere detected by qRT-PCR following the activation of EGFR pathway by treatment with epidermal growth factor (EGF) to HT-29 and LoVo cells.Results:After TF/FⅦa pathway was activated,for HT-29 cells,expressions of AREG (on mRNA level) and EREG (both on mRNA and protein level) were significantly down-regulated versus those of control group,gene expressions of AREG and EREG were 0.55 ± 0.09 vs.0.99 ± 0.09,0.67 ± 0.10 vs.1.02 ± 0.02,protein expressions of EREG were 0.54 ± 0.09 vs.1.04 ± 0.13,all P ＜ 0.05.For LoVo cells,expressions of AREG (both on mRNA and protein level) and EREG (on protein level) were significantly up-regulated versus those of control group,gene expression of AREG were 1.87 ± 0.39 vs.0.93 ± 0.23,protein expressions of AREG and EREG were 3.09 ±0.73 vs.1.11 ±0.21,1.53 ±0.19 vs.0.97 ± 0.23,all P ＜0.05.The regulating effect of AREG and EREG mRNA expression by FⅦa in HT-29 and LoVo cells could both be partly blocked by knocking down TF expression.For HT-29 cells,activation of EGFR pathway induced no significant TF mRNA expression,F Ⅶ mRNA expression was not detected.However,for LoVo cells,activation of EGFR pathway induced significantly higher mRNA expressions of both TF and FⅦ,expressions were 1.53 ± 0.23 vs.1.00 ± 0.23,53.20 ± 6.08 vs.1.00 ± 0.15,all P ＜0.05.Conclusion:In colon cancer cell LoVo,when activated,TF/FⅦa pathway and EGFR pathway could interact through upregulating the other pathway's effectors,and mutant KRAS might play a critical role in the two pathways'cross talk.

Objective To investigate the expression of matrix metalloproteinase 7(MMP-7) mRNA in LOVO cells of colon cancer induced by TF/F Ⅶ a and its signal pathway.Methods We transfected LOVO cells stably with RNAi plasmid targeting to tissue factor to get TFRNAi LOVO cells and detected efficiency of interference in TFRNAi LOVO cells based on Western blot analysis;Expression of MMP-7 was evaluated in LOVO cells treated with 100 nmol/L FⅦa in 0 h、4 h、8 h、12 h、24 h based on RT-PCR and Northern blot.Expression of MMP-7mRNA was determined in quiescent LOVO cells treated with different doses of FⅦa(0 nmol/L、10nmol/L、50 nmol/L、100 nmol/L、200 nmol/L)for 8 h based on Northern blot.Quiescent LOVO cells were treated for 0 h、4 h、8 h、12 h、16 h、24 h with 100 nmol/L FⅦa to evaluate the expression of p-P38;The expression level of MMP-7mRNA induced by 100 nmol/L FⅦa for 8 h in LOVO cells blocked by 10retool SB203580 0.5 h previously and in TFRNAi LOVO cells were measured by Northern blot.Results Northern blot analysis revealed that FⅦa markedly increased the expression of MMP-7mRNA in a time-and dose-dependent manner.Western blot analysis confirmed that FⅦa stimulates p-P38 in a time-dependent manner.SB203580 block 59.2% expression of MMP-7mRNA in LOVO cells induced by TF/FⅦa.In TFRNAi LOVO cells,the expression of MMP-7mRNA induced by TF/FⅦa was 48% less than that in normal LOVO cells.Conclusions TF/FⅦa Complex induces the expression of MMP-7mRNA in LOVO cells in vitro,possibly through P38 pathway.

OBJECTIVETo evaluate the frequency and nature of E-cadherin gene (CDH1) germline mutations in familial gastric cancer kindreds of china.

METHODSFive familial gastric cancer kindreds of Chinese origin were screened for germline CDH1 mutations, all of them meeting the clinical criteria for hereditary diffuse gastric cancer (HDGC), by PCR-DHPLC and direct sequencing.

RESULTSA new truncating mutation in exon 10 in B family was identified, producing a stop codon at position 503 (Q503X), resulting in a truncated protein. The proband of this family had metachronous development of lobular breast and diffuse type gastric carcinoma. No protein expression was detected in the lobular breast carcinoma, indicating complete inactivation of the gene.

CONCLUSIONSA Chinese gastric cancer family with CDH1 germline truncating mutation is described for the first time, and our findings suggest that lobular breast carcinoma might be part of the tumor spectrum of HDGC.

Adult ; Breast Neoplasms ; genetics ; Cadherins ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Neoplasms, Multiple Primary ; genetics ; Neoplastic Syndromes, Hereditary ; genetics ; Pedigree ; Polymerase Chain Reaction ; Stomach Neoplasms ; genetics