New parameter in diagnosis of acute appendicitis:Platelet distribution width

AIM:To investigate the diagnostic accuracy of the mean platelet volume and platelet distribution width in acute appendicitis.METHODS:This retrospective,case-controlled study compared 295 patients with acute appendicitis(Group?Ⅰ),100 patients with other intra-abdominal infections(GroupⅡ),and 100 healthy individuals(GroupⅢ)between January 2012 and January 2013.The age,gender,and white blood cell count,neutrophil percentage,mean platelet volume,and platelet distribution width values from blood samples were compared among the groups.Statistical analyses were performed using SPSS for Windows 21.0 software.In addition,the sensitivity,specificity,positive and negative predictive values and likelihood ratios,and diagnostic accuracy were calculated.RESULTS:The mean ages of patients were 29.9±12.0years for Group?Ⅰ,31.5±14.0 years for GroupⅡ,and30.4±13.0 years for GroupⅢ.Demographic features such as age and gender were not significantly different among the groups.White blood cell count,neutrophil percentage and platelet distribution width were significantly higher in Group?Ⅰ?compared to groupsⅡandⅢ(P0.05).Diagnostically,the sensitivity,specificity and diagnostic accuracy were 73.1%,94.0%,and 78%for white blood cell count,70.0%,96.0%,and 76.0%for neutrophil percentage,29.5%,49.0%,and 34.0%for mean platelet volume,and 97.1%,93.0%,and 96.0%for platelet distribution width,respectively.The highest diagnostic accuracy detected was for platelet distribution width between Group?Ⅰ?and GroupⅢ(P0.01).CONCLUSION:Platelet distribution width analysis can be used for diagnosis of acute appendicitis without requiring additional tests,thus reducing the cost and loss of time.     

Clinicopathologic features of remnant gastric cancer over time following distal gastrectomy

AIM: To investigate remnant gastric cancer(RGC) at various times after gastrectomy, and lay a foundation for the management of RGC.METHODS: Sixty-five patients with RGC 2 years and 10 years after gastrectomy(RGC Ⅰ) and forty-nine with RGC 10 years after gastrectomy(RGC Ⅱ) who underwent curative surgery were enrolled in the study.The clinicopathologic factors, surgical outcomes, and prognosis were compared between RGC Ⅰ and RGC Ⅱ.RESULTS: There was no significant difference in surgical outcomes between RGC Ⅰ and RGC Ⅱ. For patients reconstructed with Billroth Ⅱ, significantly more patients were RGC Ⅱ compared with RGC(71.9%vs 21.2%, P 0.001), and more RGC Ⅱ patients had anastomotic site locations compared to RGC Ⅰ(31.0%vs 56.3%, P = 0.038). The five-year survival rates for the patients with RGC Ⅰ and RGC Ⅱ were 37.6%and 47.9%, respectively, but no significant difference was observed. Borrmann type and tumor stage were confirmed to be independent prognostic factors in both groups.CONCLUSION: RGC Ⅱ is located on the anastomotic site in higher frequency and more cases develop after Billroth Ⅱ reconstruction than RGC Ⅰ.     

Assessment of neovascularization within carotid plaques in patients with ischemic stroke

AIM: To assess neovascularization within human carotid atherosclerotic soft plaques in patients with ischemic stroke.METHODS: Eighty-one patients with ischemic stroke and 95 patients without stroke who had soft atherosclerotic plaques in the internal carotid artery were studied. The thickest soft plaque in each patient was examined using contrast-enhanced ultrasound. Time-intensity curves were collected from 5 s to 3 min after contrast injection. The neovascularization within the plaques in the internal carotid artery was evaluated using the ACQ software built into the scanner by 2 of the experienced investigators who were blinded to the clinical history of the patients.RESULTS: Ischemic stroke was present in 7 of 33 patients (21%) with grade I plaque, in 14 of 51 patients (28%) with grade II plaque, in 26 of 43 patients (61%) with grade III plaque, and in 34 of 49 patients (69%) with grade IV plaque (P < 0.001 comparing grade IV plaque with grade I plaque and with grade II plaque and P = 0.001 comparing grade III plaque with grade I plaque and with grade II plaque). Analysis of the time intensity curves revealed that patients with ischemic stroke had a significantly higher intensity of enhancement (IE) than those without ischemic stroke (P < 0.01). The wash-in time (WT) of plaque was significantly shorter in stroke patients (P < 0.05). The sensitivity and specificity for IE in the plaque were 82% and 80%, respectively, and for WT were 68% and 74%, respectively. There was no significant difference in the peak intensity or time to peak between the 2 groups.CONCLUSION: This study shows that the higher the grade of plaque enhancement, the higher the risk of ischemic stroke. The data suggest that the presence of neovascularization is a marker for unstable plaque.     

Seroepidemiology of Helicobacter pylori infection in elderly people in the Beijing region,China

AIM:To investigate seroepidemiology of cagA+and vacA+strains of Helicobacter pylori(H.pylori)in an elderly population in Beijing and to determine risk factors for seropositivity.METHODS:A total of 2006 elderly persons(>60years)were selected using a random cluster sampling method in different parts of the Beijing area(urban,suburban and mountainous districts).Structured questionnaires were completed during home visits,including history of H.pylori infection,history of gastrointestinal diseases,diet types,hygiene habits,occupation and economic status.Blood samples(2 mL)were collected from each participant,and serum IgG antibodies to cagA,vacA and H.pylori urease antigens were measured by immunodetection.RESULTS:The prevalence of H.pylori infection in elderly subjects was 83.4%and the typeⅠH.pylori strain infection rate was 56%.The seroprevalence for typeⅠH.pylori strain infection in urban and suburbandistricts was higher than that in the mountainous areas(P<0.001).Elderly subjects who had previously performed manual labor or were in the young-old age group(age<75 years)had a higher seroprevalence of H.pylori infection than those who had previously performed mental labor or were in the oldest-old age group(age≥75 year)(P<0.05).The typeⅠH.pylori strain infection rate in the elderly with vegetarian diets was higher than in those eating high-protein foods(P<0.001).There was no significant difference in the prevalence of H.pylori strains between male and female elderly participants(P>0.05).CONCLUSION:TypeⅠH.pylori seroprevalence is higher in elderly people.The distribution of strains of H.pylori is significantly affected by age,area and dietary habits.     

Protective effect of nitric oxide on hepatopulmonary syndrome from ischemia-reperfusion injury

AIM: To evaluate immunological protection of nitric oxide (NO) in hepatopulmonary syndrome and probable mechanisms of ischemia-reperfusion (IR) injury in rat liver transplantation.METHODS: Sixty-six healthy male Wistar rats were randomly divided into three groups (11 donor/recipient pairs). In group II, organ preservation solution was lactated Ringer’s solution with heparin 10  000/μL at 4 °C. In groups I and III, the preservation solution added, respectively, L-arginine or N^G-L-arginine methyl ester (L-NAME) (1 mmol/L) based on group II, and recipients were injected with L-arginine or L-NAME (50 mg/kg) in the anhepatic phase. Grafted livers in each group were stored for 6 h and implanted into recipients. Five rats were used for observation of postoperative survival in each group. The other six rats in each group were used to obtain tissue samples, and executed at 3 h and 24 h after transplantation. The levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF)-α and NO metabolites (NOx) were detected, and expression of NO synthase, TNF-α and intercellular adhesion molecule 1 (ICAM-1) was examined by triphosphopyridine nucleotide diaphorase histochemical and immunohistochemical staining.RESULTS: By supplementing L-arginine to strengthen the NO pathway, a high survival rate was achieved and hepatic function was improved. One-week survival rate of grafted liver recipients in group I was significantly increased (28.8 ± 36.6 d vs 4 ± 1.7 d, P < 0.01) as compared with groups II and III. Serum levels of ALT in group I were 2-7 times less than those in groups II and III (P < 0.01). The cyclic guanosine monophosphate (cGMP) levels in liver tissue and NOx in group I were 3-4 times higher than those of group II after 3 h and 24 h reperfusion, while in group III, they were significantly reduced as compared with those in group II (P < 0.01). The levels of TNF-α in group I were significantly lower than in group II after 3 h and 24 h reperfusion (P < 0.01), while being significantly higher in group III than group II (P < 0.01). Histopathology revealed more severe tissue damage in graft liver and lung tissues, and a more severe inflammatory response of the recipient after using NO synthase inhibitor, while the pathological damage to grafted liver and the recipient’s lung tissues was significantly reduced in group I after 3 h and 24 h reperfusion. A small amount of constitutive NO synthase (cNOS) was expressed in liver endothelial cells after 6 h cold storage, but there was no expression of inducible NO synthase (iNOS). Expression of cNOS was particularly significant in vascular endothelial cells and liver cells at 3 h and 24 h after reperfusion in group II, but expression of iNOS and ICAM-1 was low in group I. There was diffuse strong expression of ICAM-1 and TNF-α in group III at 3 h after reperfusion.CONCLUSION: The NO/cGMP pathway may be critical in successful organ transplantation, especially in treating hepatopulmonary syndrome during cold IR injury in rat orthotopic liver transplantation.     

Role of serum carcinoembryonic antigen in the detection of colorectal cancer before and after surgical resection

AIM: To determine whether serum levels of carcinoembryonic antigen (CEA) correlate with the presence of primary colorectal cancer (CRC), and/or recurrent CRC following radical resection.METHODS: A total of 413 patients with CRC underwent radical surgery between January 1998 and December 2002 in our department and were enrolled in this study. The median follow-up period was 69 mo (range, 3-118 mo), and CRC recurrence was experienced by 90/413 (21.8%) patients. Serum levels of CEA were assayed preoperatively, and using a cutoff value of 5 ng/mL, patients were divided into two groups, those with normal serum CEA levels (e.g., ≤ 5 ng/mL) and those with elevated CEA levels (> 5 ng/mL).RESULTS: The overall sensitivity of CEA for the detection of primary CRC was 37.0%. The sensitivity of CEA according to stage, was 21.4%, 38.9%, and 41.7% for stages I-III, respectively. Moreover, for stage II and stage III cases, the 5-year disease-free survival rates were reduced for patients with elevated preoperative serum CEA levels (P < 0.05). The overall sensitivity of CEA for detecting recurrent CRC was 54.4%, and sensitivity rates of 36.6%, 66.7%, and 75.0% were associated with cases of local recurrence, single metastasis, and multiple metastases, respectively. In patients with normal serum levels of CEA preoperatively, the sensitivity of CEA for detecting recurrence was reduced compared with patients having a history of elevated CEA prior to radical resection (32.6% vs 77.3%, respectively, P < 0.05).CONCLUSION: CRC patients with normal serum CEA levels prior to resection maintained these levels during CRC recurrence, especially in cases of local recurrence vs cases of metastasis.     

Effect of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in colorectal liver metastases

AIM:To evaluate the influence of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in liver metastases of stage Ⅳ colorectal cancer(CRC) patients.METHODS:Using Real Time-PCR,enzyme-linked immunosorbent assay,Western Blots and immunohistochemistry,we have analyzed the expression of CCL20,CCR6 and proliferation marker Ki-67 in colorectal liver metastasis(CRLM) specimens from stage Ⅳ CRC patients who received preoperative FOLFOX chemotherapy(n = 53) and in patients who did not receive FOLFOX chemothera...     

Perforated midgut diverticulitis: Revisited

AIM: To study and provide data on the evolution of medical procedures and outcomes of patients suffering from perforated midgut diverticulitis.METHODS: Three data sources were used: the Medline and Google search engines were searched for case reports on one or more patients treated for perforated midgut diverticulitis (Meckel’s diverticulitis excluded) that were published after 1995. The inclusion criterion was sufficient individual patient data in the article. Both indexed and non-indexed journals were used. Patients treated for perforated midgut diverticulitis at Vestfold Hospital were included in this group. Data on symptoms, laboratory and radiology results, treatment modalities, surgical access, procedures, complications and outcomes were collected. The Norwegian patient registry was searched to find patients operated upon for midgut diverticulitis from 1999 to 2007. The data collected were age, sex, mode of access, surgical procedure performed and number of patients per year. Historical controls were retrieved from an article published in 1995 containing pertinent individual patient data. Statistical analysis was done with SPSS software.RESULTS: Group I: 106 patients (48 men) were found. Mean age was 72.2 ± 13.1 years (mean ± SD). Age or sex had no impact on outcomes (P = 0.057 and P = 0.771, respectively). Preoperative assessment was plain radiography in 53.3% or computed tomography (CT) in 76.1%. Correct diagnosis was made in 77.1% with CT, 5.6% without (P = 0.001). Duration of symptoms before hospitalization was 3.6 d (range: 1-35 d), but longer duration was not associated with poor outcome (P = 0.748). Eighty-six point eight percent of patients underwent surgery, 92.4% of these through open access where 90.1% had bowel resection. Complications occurred in 19.2% of patients and 16.3% underwent reoperation. Distance from perforation to Treitz ligament was 41.7 ± 28.1 cm. At surgery, no peritonitis was found in 29.7% of patients, local peritonitis in 47.5%, and diffuse peritonitis in 22.8%. Peritonitis grade correlated with the reoperation rate (r = 0.43). Conservatively treated patients had similar hospital length of stay as operated patients (10.6 ± 8.3 d vs 10.7 ± 7.9 d, respectively). Age correlated with hospital stay (r = 0.46). No difference in outcomes for operated or nonoperated patients was found (P = 0.814). Group II: 113 patients (57 men). Mean age 67.6 ± 16.4 years (range: 21-96 years). Mean age for men was 61.3 ± 16.2 years, and 74.7 ± 12.5 years for women (P = 0.001). Number of procedures per year was 11.2 ± 0.9, and bowel resection was performed in 82.3% of patients. Group III: 47 patients (21 men). Patient age was 65.4 ± 14.4 years. Mean age for men was 61.5 ± 17.3 years and 65.3 ± 14.4 years for women. Duration of symptoms before hospitalization was 6.9 d (range: 1-180 d). No patients had a preoperative diagnosis, 97.9% of patients underwent surgery, and 78.3% had multiple diverticula. Bowel resection was performed in 67.4% of patients, and suture closure in 32.6%. Mortality was 23.4%. There was no difference in length of history or its impact on survival between Groups I and III (P = 0.241 and P = 0.198, respectively). Resection was more often performed in Group I (P = 0.01). Mortality was higher in Group III (P = 0.002).CONCLUSION: In cases with contained perforation, conservative treatment gives satisfactory results, laparoscopy with lavage and drainage can be attempted and continued with a conservative course.     

Correlation between mitochondrial TRAP-1 expression and lymph node metastasis in colorectal cancer

AIM: To evaluate the effect of mitochondrial tumor necrosis factor receptor-associated protein-1 (TRAP-1) on the lymph node metastasis (LNM) in Chinese colorectal cancer (CRC) patients, and develop potential LNM-associated biomarkers for CRC using quantitative real-time polymerase chain reaction (RT-PCR) analysis.METHODS: Differences in mitochondrial TRAP-1 gene expression between primary CRC with LNM (LNM CRC) and without LNM (non-LNM CRC) were assessed in 96 Chinese colorectal carcinoma samples using quantitative RT-PCR analysis, Western blotting, and confirmed with immunohistochemical assay. The relationship between clinicopathological parameters and potential diagnostic biomarkers was also examined.RESULTS: TRAP-1 was significantly upregulated in LNM CRC compared with non-LNM CRC, which was confirmed by RT-PCR, Western blotting and immunohistochemical assay. The expression of TRAP-1 in two different metastatic potential human colorectal cancer cell lines, LoVo and HT29, was analyzed with Western blotting. The expression level of TRAP-1 was dramatically higher in LoVo than in HT29. Overexpression of TRAP-1 was significantly associated with LNM (90.2% in LNM group vs 22% in non-LNM group, P < 0.001), the advanced tumor node metastasis stage (89.1% in LNM group vs 26.9% in non-LNM group, P < 0.001), the increased 5-year recurrence rate (82.7% in LNM group vs 22.6% in non-LNM group, P < 0.001) and the decreased 5-year overall survival rate (48.4% in LNM vs 83.2% in non-LNM group, P < 0.001). Univariate and multivariate analyses indicated that TRAP-1 expression was an independent prognostic factor for recurrence and survival of CRC patients (Hazard ratio of 2.445 in recurrence, P = 0.017; 2.867 in survival, P = 0.028).CONCLUSION: Mitochondria TRAP-1 affects the lymph node metastasis in CRC, and may be a potential biomarker for LNM and a prognostic factor in CRC. Over-expression of TRAP-1 is a predictive factor for the poor outcome of colorectal cancer patients.     

Histological mixed-type as an independent prognostic factor in stageⅠgastric carcinoma

AIM: To evaluate the clinicopathological features of mixed-type gastric cancer and their influence on prognosis of mixed-type stageⅠgastric cancer.METHODS: We analyzed 446 patients who underwent curative gastrectomy for stageⅠgastric cancer between 1999 and 2009. The patients were divided into two groups: those with differentiated or undifferentiated cancer(non-mixed-type, n = 333) and those with a mixture of differentiated and undifferentiated cancers(mixed-type, n = 113).RESULTS: The overall prevalence of mixed-type gastric cancer was 25.3%(113/446). Compared with patients with non-mixed-type gastric cancer, those with mixedtype gastric cancer tended to be older at onset(P = 0.1252) and have a higher incidence of lymph node metastasis(P = 0.1476). They also had significantly larger tumors(P 0.0001), more aggressive lymphatic invasion(P = 0.0011), and deeper tumor invasion(P 0.0001). In addition, they exhibited significantly worse overall survival rates than did patients with non-mixedtype gastric cancer(P = 0.0026). Furthermore, mixedtype gastric cancer was independently associated with a worse outcome in multivariate analysis [P = 0.0300, hazard ratio = 11.4(1.265-102.7)].CONCLUSION: Histological mixed-type of gastric cancer contributes to malignant outcomes and highlight its usefulness as a prognostic indicator in stageⅠgastric cancer.     

Outcome after gastrectomy in gastric cancer patients with type 2 diabetes

AIM: To evaluate the prognosis of type II diabetes mellitus (T2DM) after gastrectomy and related factors in gastric cancer patients.METHODS: 403 gastric cancer patients with T2DM were studied, who underwent gastrectomy between May 2003 and September 2009. A review of medical records and telephone interviews was performed in this cross-sectional study. The factors included in the statistical analysis were as follows: gender, age, type of surgery, preoperative body mass index (BMI), current BMI, BMI reduction ratio, preoperative insulin or oral diabetic medicine requirement, follow-up duration, and current state of diabetes. Assessment of diabetes status after surgery was classified into four categories according to the change in hypoglycemic agents after surgery and present status of T2DM: resolution, improvement, same, and worse.RESULTS: The mean follow-up duration was 33.7 mo (± 20.6 mo), preoperative BMI was 24.7 kg/m² (± 3.0 kg/m²), and BMI reduction ratio was 9.8% (± 8.6%). After surgery, T2DM was cured in 58 patients (15.1%) and was improved in 117 patients (30.4%). According to the type of surgery, the BMI reduction ratio was significantly higher in the total gastrectomy and Roux-en-Y reconstruction group [14.2% ± 9.2% vs 9.2% ± 7.7% (Billroth II group), P < 0.001] and significantly lower in the subtotal gastrectomy and Billroth I reconstruction group [7.6% ± 8.0%, 9.2% ± 7.7% (Billroth II group), P < 0.001]. The BMI reduction ratio, follow-up duration after surgery, type of surgery, extent of gastrectomy, and performance of duodenal bypass were significantly correlated to the course of T2DM (P < 0.05). The BMI reduction ratio was the most influential factor on T2DM status. In a subgroup analysis of patients with a BMI reduction ratio of 10% or less (n = 206), T2DM was cured in 15 (7.6%) patients and was improved in 57 (28.8%) patients after surgery, and only the duration of surgery was significantly correlated to T2DM status (P = 0.022).CONCLUSION: The course of T2DM was significantly correlated to the BMI reduction ratio but not to the type of surgery without a significant change in BMI.     

Oxymatrine liposome attenuates hepatic fibrosis via targeting hepatic stellate cells

AIM: To investigate the potential mechanism of Arg-Gly-Asp (RGD) peptide-labeled liposome loading oxymatrine (OM) therapy in CCl₄-induced hepatic fibrosis in rats.METHODS: We constructed a rat model of CCl₄-induced hepatic fibrosis and treated the rats with different formulations of OM. To evaluate the antifibrotic effect of OM, we detected levels of alkaline phosphatase, hepatic histopathology (hematoxylin and eosin stain and Masson staining) and fibrosis-related gene expression of matrix metallopeptidase (MMP)-2, tissue inhibitor of metalloproteinase (TIMP)-1 as well as type I procollagen via quantitative real-time polymerase chain reaction. To detect cell viability and apoptosis of hepatic stellate cells (HSCs), we performed 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide assay and flow cytometry. To reinforce the combination of oxymatrine with HSCs, we constructed fluorescein-isothiocyanate-conjugated Arg-Gly-Asp peptide-labeled liposomes loading OM, and its targeting of HSCs was examined by fluorescent microscopy.RESULTS: OM attenuated CCl₄-induced hepatic fibrosis, as defined by reducing serum alkaline phosphatase (344.47 ± 27.52 U/L vs 550.69 ± 43.78 U/L, P < 0.05), attenuating liver injury and improving collagen deposits (2.36% ± 0.09% vs 7.70% ± 0.60%, P < 0.05) and downregulating fibrosis-related gene expression, that is, MMP-2, TIMP-1 and type I procollagen (P < 0.05). OM inhibited cell viability and induced apoptosis of HSCs in vitro. RGD promoted OM targeting of HSCs and enhanced the therapeutic effect of OM in terms of serum alkaline phosphatase (272.51 ± 19.55 U/L vs 344.47 ± 27.52 U/L, P < 0.05), liver injury, collagen deposits (0.26% ± 0.09% vs 2.36% ± 0.09%, P < 0.05) and downregulating fibrosis-related gene expression, that is, MMP-2, TIMP-1 and type I procollagen (P < 0.05). Moreover, in vitro assay demonstrated that RGD enhanced the effect of OM on HSC viability and apoptosis.CONCLUSION: OM attenuated hepatic fibrosis by inhibiting viability and inducing apoptosis of HSCs. The RGD-labeled formulation enhanced the targeting efficiency for HSCs and the therapeutic effect.     

Involvement of 90-kuD ribosomal S6 kinase in collagen type I expression in rat hepatic fibrosis

AIM： To investigate the relationship between 90-kuD ribosomal $6 kinase （pg0RSK） and collagen type I expression during the development of hepatic fibrosis in vivo and in vitro.METHODS： Rat hepatic fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. The protein expression and cell location of p90RSK and their relationship with collagen type I were determined by co-immunofluoresence and confocal microscopy.Subsequently, RNAi strategy was employed to silence p90RSK mRNA expression in HSC-T6, an activated hepatic stellate cell （HSC） line. The expression of collagen type I in HSC-T6 cells was assessed by Western blotting and real-time polymerase chainreaction. Furthermore, HSCs were transfected with expression vectors or RNAi constructs of p90RSK to increase or decrease the p90RSK expression, thencollagen type I promoter activity in the transfected HSCs was examined by reporter assay. Lastly HSC-T6 cells transfected with p90RSK siRNA was treated withor without platelet-derived growth factor （PDGF）-BB at a final concentration of 20μg/L and the cell growthwas determined by MTS conversion.RESULTS： In fibrotic liver tissues, p90RSK was over-expressed in activated HSCs and had a significantpositive correlation with collagen type I levels.In HSC-T6 cells transfected with RNAi targeted top90RSK, the expression of collagen type I was down-regulated （61.8% in mRNA, P 〈 0.01, 89.1% inprotein, P 〈 0.01）. However, collagen type ] promoteractivity was not increased with over-expression of p90RSK and not decreased with low expression either,compared with controls in the same cell line （P = 0.076）.Furthermore, p90RSK siRNA exerted the inhibitionof HSC proliferation, and also abolished the effect of PDGF on the HSC proliferation.CONCLUSION： p90RSK is over-expressed in activatedHSCs and involved in regulating the abnormalexpression of collagen type I through initiating theproliferation of HSCs.     

Characteristics and long-term prognosis of patients with rectal neuroendocrine tumors

AIM:To analyze the clinicopathologic characteristics and prognostic factors of rectal neuroendocrine tumors.METHODS:The records of 48 patients with rectal neuroendocrine tumors who were treated at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,Beijing,from March 2004 to September 2009were retrospectively reviewed.The clinicopathological data were extracted and analyzed,and patients were followed-up by telephone or follow-up letter to determine their survival status.Follow-up data were available for all 48 patients.Uni-and multivariate Cox regression analyses were performed to determine the prognostic factors significantly associated with overall survival.RESULTS:The tumors occurred mostly in the middle and lower rectum,and the most prominent symptoms experienced by patients were hematochezia and diarrhea.The median distance between the tumors andthe anal edges was 5.0±2.257 cm,and the median diameter of the tumors was 0.8±1.413 cm.The major pathological type was a typical carcinoid tumor,which accounted for 93.8%(45/48)of patients.Tumor-nodemetastasis(TNM)stagesⅠ,Ⅱ,ⅢandⅣtumors accounted for 78.8%,3.9%,9.6%and 7.7%of patients,respectively.The main treatment method,in 72.9%(35/48)of patients,was transanal extended excision.The 1-,3-and 5-year survival rates of the whole group of patients were 100%,93.7%,and 91.3%,respectively.Univariate analysis showed that age(P=0.032),tumor diameter(P<0.001),histological type(P<0.001),TNM stage(P<0.001),and surgical approach(P=0.002)were all prognostic factors.On multivariate analysis,only the pathological type was shown to be an independent prognostic factor(HR=2.797,95%CI:1.676-4.668,P=0.004).CONCLUSION:In patients with rectal neuroendocrine tumors,TNM stage Ⅰ is the most common stage found,and lymph node or distant metastases are rarely seen.The pathological type of the tumor is an independent prognostic factor.     

Stimulation of oval cell and hepatocyte proliferation by exogenous bombesin and neurotensin in partially hepatectomized rats

AIM: To investigate the effect of the neuropeptides bombesin (BBS) and neurotensin (NT) on oval cell proliferation in partially hepatectomized rats not pretreated with a known hepatocyte inhibitor.METHODS: Seventy male Wistar rats were randomly divided into five groups: I = controls, II = sham operated, III = partial hepatectomy 70% (PHx), IV = PHx + BBS (30 μg/kg per day), V = PHx + NT (300 μg/kg per day). Forty eight hours after liver resection, portal endotoxin levels and hepatic glutathione redox state were determined. α-fetoprotein (AFP) mRNA (in situ hybridisation), cytokeratin-19 and Ki67 antigen expression (immunohistochemistry) and apoptosis (TUNEL) were evaluated on liver tissue samples. Cells with morphological features of oval cells that were cytokeratin-19 (+) and AFP mRNA (+) were scored in morphometric analysis and their proliferation was recorded. In addition, the proliferation and apoptotic rates of hepatocytes were determined.RESULTS: In the control and sham operated groups, oval cells were significantly less compared to groups III, IV and V (P < 0.001). The neuropeptides BBS and NT significantly increased the proliferation of oval cells compared to group III (P < 0.001). In addition, BBS and NT induced a significant increase of hepatocyte proliferation (P < 0.001), whereas it decreased their apoptotic activity (P < 0.001) compared to group III. BBS and NT significantly decreased portal endotoxemia (P < 0.001) and increased the hepatic GSH: GSSG ratio (P < 0.05 and P < 0.001, respectively) compared to group III.CONCLUSION: BBS and NT stimulated oval cell proliferation in a model of liver regeneration, without use of concomitant suppression of hepatocyte proliferation as oval cell activation stimuli, and improved the hepatocyte regenerative response. This peptides-induced combined stimulation of oval cell and hepatocyte proliferation might serve as a possible treatment modality for several liver diseases.     

Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia

AIM:To determine the expression of neurokinin-1receptor(NK-1R),phosphorylated epidermal growth factor receptor(p EGFR),cyclooxygenase-2(Cox-2),and vitamin D receptor(VDR)in normal,inflammatory bowel disease(IBD),and colorectal neoplasia tissues from Puerto Ricans.METHODS:Tissues from patients with IBD,colitisassociated colorectal cancer(CAC),sporadic dysplasia,and sporadic colorectal cancer(CRC),as well as normal controls,were identified at several centers in Puerto Rico.Archival formalin-fixed,paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R,p EGFR,Cox-2,and VDR.Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a4-point scale that assessed intensity of staining.Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia,in addition to the areas of cancer,within each tissue.Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test.The mean scores for normal tissues and tissues with IBD,dysplasia,CRC,and CAC were calculatedand statistically compared using one-way analysis of variance and Dunnett’s multiple comparisons test.Correlations between protein expression patterns were analyzed with the Pearson’s product-moment correlation coefficient.Data are presented as mean±SE.RESULTS:On average,patients with IBD were younger(34.60±5.81)than normal(63.20±6.13,P0.01),sporadic dysplasia(68.80±4.42,P0.01),sporadic cancer(74.80±4.91,P0.001),and CAC(57.50±5.11,P0.05)patients.NK-1R in cancer tissue(sporadic CRC,1.73±0.34;CAC,1.57±0.53)and sporadic dysplasia(2.00±0.45)were higher than in normal tissues(0.73±0.19).p EGFR was significantly increased in sporadic CRC(1.53±0.43)and CAC(2.25±0.47)when compared to normal tissue(0.07±0.25,P0.05,P0.001,respectively).Cox-2 was significantly increased in sporadic colorectal cancer(2.20±0.23 vs 0.80±0.37 for normal tissues,P0.05).In comparison to normal(2.80±0.13)and CAC(2.50±0.33)tissues,VDR was significantly decreased in sporadic dysplasia(0.00±0.00,P0.001 vs normal,P0.001 vs CAC)and sporadic CRC(0.47±0.23,P0.001 vs normal,P0.001 vs CAC).VDR levels negatively correlated with NK-1R(r=-0.48)and p EGFR(r=-0.56)in normal,IBD,sporadic dysplasia and sporadic CRC tissue,but not in CAC.CONCLUSION:Immunohistochemical NK-1R and p EGFR positivity with VDR negativity can be used to identify areas of sporadic colorectal neoplasia.VDR immunoreactivity can distinguish CAC from sporadic cancer.     

Preoperative carcinoembryonic antibody is predictive of distant metastasis in pathologically T1 colorectal cancer after radical surgery

AIM:To identify the predictors of distant metastasis in pathologically T1(pT1)colorectal cancer(CRC)after radical resection. METHODS:Variables including age,gender,preoperative carcinoembryonic antibody(CEA)level,tumor location,tumor size,lymph node status,and histological grade were recorded.Patients with and without metastasis were compared with regard to age,gender,CEA level and pathologic tumor characteristics using the independent t test orχ 2 test,as appropriate.Risk factors were determined by logistic regression analysis. RESULTS:Metastasis occurred in 6(3.8%)of the 159 patients during a median follow-up of 67.0(46.5%) mo.The rates of distant metastasis in patients with pT1 cancer of the colon and rectum were 6.7%and 2.9%, respectively(P<0.001).The rates of distant metastasis between male and female patients with T1 CRC were 6.25%and 1.27%,respectively(P<0.001).The most frequent site of distant metastasis was the liver. Age(P=0.522),gender(P=0.980),tumor location(P =0.330),tumor size(P=0.786),histological grade(P =0.509),and high serum CEA level(P=0.262)were not prognostic factors for lymph node metastasis.Univariate analysis revealed that age(P=0.231),gender(P =0.137),tumor location(P=0.386),and tumor size (P=0.514)were not risk factors for distant metastasis after radical resection for T1 colorectal cancer.Postoperative metastasis was only significantly correlated with high preoperative serum CEA level(P=0.001).Using multivariate logistic regression analysis,high preoperative serum CEA level(P=0.004;odds ratio 15.341; 95%CI 2.371-99.275)was an independent predictor for postoperative distant metastasis. CONCLUSION:The preoperative increased serum CEA level is a predictive risk factor for distant metastasis in CRC patients after radical resection.Adjuvant chemotherapy may be necessary in such patients,even if they have pT1 colorectal cancer.     

Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer

AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) population.METHODS: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage Ⅰ-Ⅲ CRC and examined associations of these mutations with disease-free survival(DFS) and overall survival(OS) using uni- and multivariate Cox proportional hazards models.RESULTS: KRAS and BRAF mutations were detected in 312(38%) of 812 and 40(5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males(P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender(P = 0.006), proximal tumor location(P 0.001), mucinous or poorly differentiated histology(P 0.001), and MSI-high tumors(P 0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS(HR = 1.35; 95%CI: 1.03-1.75) and OS(HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS(HR = 2.20; 95%CI: 1.19-4.06) and OS(HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS.CONCLUSION: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, inJapanese patients with curatively resected CRC.