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 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 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 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

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

BACKGROUNDNowadays, there is a remarkable rise in resectability rate of periampullary adenocarcinoma and the mortality and morbidity of the pancreaticoduodenectomy procedure have been reduced remarkably, while the 5 year survival rates of patients with carcinoma of the head of the pancreas are still below 25%. We conducted this retrospective study to evaluate the clinical outcome of radical pancreaticoduodenectomy with extended retroperitoneal lymphadenectomy as a surgical therapy for adenocarcinoma of the head of the pancreas.

METHODSTwenty cases with adenocarcinoma of the head of the pancreas were treated by standard pancreaticoduodenectomy (removing only the peripancreatic lymph nodes en bloc with the tumour) from 1994 to 1997, and 46 cases with the same disease underwent extended retroperitoneal lymphadenectomy associated with standard pancreaticoduodenectomy from 1998 to 2002. The patients for whom there were insufficient follow-up data, or who had received postoperative adjuvant therapy, were excluded from the analysis. Clinical and pathological parameters of both groups were reviewed. The postoperative morbidity, mortality and survival data were compared statistically.

RESULTSDemographic and histopathological characteristics were similar in the two groups of patients. Performance of the extended lymphadenectomy lengthened the procedure. The mean total number of lymph nodes resected was significantly higher in the radical group (P < 0.05). Of the 46 cases in the radical group, 26% (12/46) had metastatic adenocarcinoma in the resected retroperitoneal lymph nodes. There was one perioperative death in the standard group, and two in the radical group. Postoperative diarrhoea and lymphatic leakage were only observed in the radical group. Transfusion requirements and postoperative morbidity rates did not differ between the two groups. The 1-, 2- and 3-year survival rates were 63%, 32% and 21% respectively in the standard group, and 66%, 38% and 21% in the radical group. No statistically significant difference was found between the groups. When subgroups of node positive patients were analysed, the 1-, 2- and 3-year survival rates were 42%, 17% and 8% respectively in the standard group, and 65%, 32% and 16% in the radical group. Better survival was observed in the first 2 years after operation in the radical group, but no survival differences were seen after 2 years post operation.

CONCLUSIONSThe addition of an extended lymphadenectomy to a pancreaticoduodenectomy did not significantly increase morbidity rates, but was associated with an early survival advantage.

Adenocarcinoma ; mortality ; surgery ; Adult ; Aged ; Female ; Humans ; Lymph Node Excision ; Male ; Middle Aged ; Pancreatic Neoplasms ; mortality ; surgery ; Pancreaticoduodenectomy ; Retroperitoneal Space ; Retrospective Studies ; Survival Rate ; Treatment Outcome

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

BACKGROUNDIt is a challenge for the surgeons to accurately diagnose the pancreatic masses preoperatively, which decides the choice of surgical managements and subsequently results in different survivor outcomes, operative complications, and mortality rates. The purposes of this study were to evaluate the diagnostic role that intra-operative puncture biopsy may play in pancreatic masses and to explore the relevant factors influencing the diagnosis.

METHODSA retrospective study was performed on 94 in-patients admitted to Peking University First Hospital for pancreatic masses during the period from June 1994 to December 2007. They all underwent intra-operative puncture biopsy during exploratory laparotomy. The sensitivity and specificity of intra-operative puncture biopsy were calculated and the relevant factors to the diagnosis of biopsy were selected for the statistical analysis.

RESULTSThe overall sensitivity, specificity, positive predictive value, and negative predictive value of intra-operative puncture biopsy were 76.0%, 94.7%, 98.3% and 50.0%, respectively. The analysis of bivariate correlations showed that the size of the pancreatic masses (P = 0.000), the number of puncture biopsies (P = 0.000), and the presence of pancreatic fibrosis (P = 0.012) had statistic significance for the diagnosis. But the multivariate analysis identified the size of the pancreatic masses (P = 0.004) and the number of puncture biopsies (P = 0.000) as independent predictive factors for intra-operative puncture biopsy. In addition, as the number of puncture biopsies increased, the sensitivity and specificity of diagnosis was improved (P = 0.000). The sensitivity and specificity of intra-operative puncture biopsy were found to be lower for the pancreatic masses less than 25 mm compared with the masses larger than 25 mm (P = 0.000). It was noted, however, that even if the masses were less than 25 mm, the sensitivity and specificity could be improved significantly as the number of puncture biopsies reached 3 to 6 (P = 0.007).

CONCLUSIONSIntra-operative puncture biopsy is simple and accurate for qualitatively differentiating various types of pancreatic masses. Three to 4 biopsies could significantly improve the diagnostic effect for pancreatic masses, even if the masses are less than 25 mm in size.

Aged ; Biopsy, Needle ; methods ; Female ; Humans ; Male ; Middle Aged ; Pancreas ; surgery ; Pancreatic Diseases ; diagnosis ; Pancreatic Neoplasms ; diagnosis ; Retrospective Studies ; Sensitivity and Specificity

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.