Combined analysis of imaging tumor capsule with imaging tumor size guides the width of resection margin for solitary hepatocellular carcinoma.

BACKGROUND: The optimal width of resection margin (RM) for hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the value of imaging tumor capsule (ITC) and imaging tumor size (ITS) in guiding RM width for patients with HCC. METHODS: Patients who underwent hepatectomy for HCC in our center were retrospectively reviewed. ITC (complete/incomplete) and ITS (≤ 3 cm/> 3 cm) were assessed by preoperative magnetic resonance imaging (MRI). Using subgroup analyses based on ITC and ITS, the impact of RM width [narrow RM (< 5 mm)/wide RM (≥ 5 mm)] on recurrence-free survival (RFS), overall survival (OS), and RM recurrence was analyzed. RESULTS: A total of 247 patients with solitary HCC were included. ITC and ITS were independent predictors for RFS and OS in the entire cohort. In patients with ITS ≤ 3 cm, neither ITC nor RM width showed a significant impact on prognosis, and the incidence of RM recurrence was comparable between the narrow RM and wide RM groups (15.6% vs. 4.3%, P = 0.337). In patients with ITS > 3 cm and complete ITC, the narrow RM group exhibited comparable RFS, OS, and incidence of RM recurrence with the wide RM group (P = 0.606, 0.916, and 0.649, respectively). However, in patients with ITS > 3 cm and incomplete ITC, the wide RM group showed better RFS and OS and a lower incidence of RM recurrence compared with the narrow RM group (P = 0.037, 0.018, and 0.046, respectively). CONCLUSIONS: As MRI-based preoperative markers, conjoint analysis of ITC with ITS aids in determining RM width for solitary HCC patients. Narrow RM is applicable in patients with ITS ≤ 3 cm regardless of ITC status and in those with ITS > 3 cm and complete ITC. Wide RM is preferred in those with ITS > 3 cm and incomplete ITC.

Alpha-Lipoic Acid Suppresses Extracellular Histone-Induced Release of the Infammatory Mediator Tumor Necrosis Factor-α by Macrophages.

BACKGROUND/AIMS: This study investigated signaling pathways via which extracellular histones induce the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) release from the macrophage cell line RAW 264.7 and the anti-inflammatory efficacy of the antioxidant alpha-lipoic acid (ALA). METHODS: ELISA and western blotting analyses were conducted to detect the release of TNF-α from histone-stimulated RAW 264.7 macrophages and the associated phospho-activation of MAPKs (ERK and p38) and NF-κB p65. The effects of ALA on the release of TNF-α and phospho-activation of the MAPKs and NF-κB p65 were studied. P < 0.05 was considered statistically significant. RESULTS: Extracellular histones dose-dependently induced TNF-α release from RAW 264.7 cells and increased the phosphorylation of p38, ERK, and NF-κB p65. TNF-α release was markedly suppressed by p38, ERK, and NF-kB inhibitors. ALA reduced histone-induced TNF-α release, ERK/p38 MAPK activation, and NF-kB activation without affecting macrophage viability. CONCLUSION: Histones induce TNF-α release from macrophages by activating the MAPK and NF-kB signaling pathways, while ALA suppresses this response by inhibiting ERK, p38 and NF-kB. These findings identify potentially critical inflammatory signaling pathways in sepsis and molecular targets for sepsis treatment.

[Primary diffuse large B-cell non-Hodgkin's lymphoma of the small intestine: clinicopathologic features, management, and prognosis in 24 patients].

OBJECTIVE: To investigate the clinicopathological features of primary diffuse large B-cell lymphomas (DLBCLs) of the small intestine, CD10 expression, and their relationship to prognosis. METHODS: Twenty-four cases of small intestinal DLBCLs were studied clinically and pathologically. All cases were staged according to the Ann Arbor classification of lymphoma. RESULTS: Fifteen cases (62.5%) were at stages I and II, and nine cases (37.5%) at stages III and IV. The Karnofsky performance status ranged from 40% to 100% (mean 75.5%). Twenty cases (83.3%) received surgical resection, sixteen cases (66.7%) received chemotherapy, and no patient received radiotherapy. Seven of 19 cases (36.8%) were CD10+. Although there was no statistically significant difference(P = 0.28) in therapy result between the CD10+ and CDO1--groups, patients with CD10+ lymphoma more frequently presented with stages I compared with those with CD10 - lymphoma (P = 0.013). Follow-up information was available in 19 cases ranging from 1 to 111 months (mean 32.7 months). Five cases died of the disease. The mortality rate was 26.3%. The analysis of survival rate showed a longer overall survival duration in the stage I and II group compared with that of the stage III and IV group ( P = 0.0197 ) , but there was no significant difference between CD10+ and CD1- groups. CONCLUSION: The primary small intestnal diffuse large B cell lymphoma patients at stage I and II respond better to therapy including surgical resection and chemotherapy than those at stage III and IV. CD10+ expression is more common in stage I lymphomas.

[Research of rat small intestinal mesentery lymphoid tissue stimulating allograft mixed lymphocyte reaction].

OBJECTIVE: To evaluate the effect of the small intestinal mesenteric lymphoid tissues stimulating mixed lymphocyte reaction with dendritic cells (DC) and peripheral blood monocyte cells (PBMC), and observe the changes of the MHC molecular expression on DC. METHODS: DC, PBMC and mixed lymphocyte were separated to culture from SD rats. Lymphoid tissue suspension was adopted from small intestinal mesentery of Wistar rats. In the mixed lymphocyte reaction (MLR), the cellular proliferation of small intestinal mesenteric lymphoid tissue antigen act on DC and PBMC was detected with cell counting of CCK-8 assay, the same assay used in small intestinal mesenteric lymphoid tissue antigen and ovalbumin (OVA) acting on DC. FACS analysis was performed after lymphoid tissue suspension stimulating DC to observe the MHC molecular expression. RESULTS: In the lymphoid tissue suspension, 91% of the cells was lymphocyte, others including granulocyte, plasmocyte, epithelium. The effect of stimulating mixed lymphocyte proliferation were higher in DC groups than in PBMC groups with the small intestinal mesenteric lymphoid tissue (P < 0.05). In the proportion of DC and mixed lymphocyte >or= 1:100 groups, the mixed lymphocyte proliferation were higher in the small intestinal mesenteric lymphoid tissues groups than in the OVA groups (P < 0.05). After stimulated by the small intestinal mesenteric lymphoid tissue, DC expressed higher MHC-I and -II molecules than control groups. CONCLUSIONS: The small intestinal mesenteric lymphoid tissue has high antigenicity; the antigen presenting ability of DC was much stronger than granulocytes; DC expresses high MHC-I and MHC-II molecules after stimulated by mixed lymphoid tissue suspension.

[Clinical analysis of infectious complications following abdominal cluster transplantation].

OBJECTIVE: To investigate the characteristic and management of postoperative infection in abdominal cluster transplantation. METHODS: Preliminary experience of two cases of abdominal cluster transplantation including small intestine was reviewed. RESULTS: Combination of five immunosuppressive agents based on tacrolimus was used. Severe Gram-negative bacillus infections occurred. The majority of invasive fungal infections was due to Candida species. Cytomegalovirus (CMV) infection increased monocytes and caused eosinopenia and an inversion of the CD4(+) to CD8(+) cell ratio in recipient I, and human CMV matrix proteins pp71 (CMV-pp71) was detected and identified in bile by PCR. Microabscesses in liver transplant biopsies were presented. CONCLUSIONS: Infectious complications after cluster transplantation were complicated. Strategies to optimize the immunity suppression protocol and early diagnosis and treatment will be important to reduce infection after abdominal cluster transplantation.

Protective effect of sodium nitroprusside on the rat small intestine transplanted mucosa.

The intestinal mucosal epithelium is extremely susceptible to even brief periods of ischemia. Mucosal barrier damage, which is associated with ischemia/reperfusion (I/R) injury and consequently bacterial translocation, remains a major obstacle for clinically successful small bowel transplantation (SBT). Previous studies have demonstrated a protective effect of nitric oxide (NO) on other transplanted organs and NO mediated intestinal protection has also been reported in vitro. The aim of this study was to evaluate the effect of sodium nitroprusside (SNP), NO donor, on graft mucosal histology and molecular markers of function after SBT in rats. We used SNP in different period of heterotopic SBT rats. The groups consisted of SBT, pre-SNP group, and post-SNP group. Interestingly, the pre-SNP graft samples exhibited less damage compared to the SBT and post-SNP samples. In addition, mucosal samples from the pre-SNP group showed higher Na(+)-K(+)-ATPase activity and higher levels of laminin expression compared to the SBT and post-SNP samples. The findings of the present study reveal that SNP given before graft ischemia/reperfusion injury has a protective effect on mucosal histology and molecular markers of function in the transplanted small intestine.

Could Tumor Size Be A Predictor for Papillary Thyroid Microcarcinoma: a Retrospective Cohort Study.

BACKGROUND: Central lymph node metastasis(CLNM) is common in papillary thyroid microcarcinoma (PTMC). The aim of this study was to define the pathohistologic risk grading based on surgical outcomes. MATERIALS AND METHODS: Statistical analysis was performed to figure out the optimal cut-off values of size in preoperative ultrasound images for defining the risk of CLNM in papillary thyroid microcarcinoma. Receiver operating characteristic curves (ROC) studies were carried out to determine the cutoff value(s) for the predictor(s). All the patients were divided into two groups according to the above size and the clinic-pathological and immunohistochemical parameters were compared to determine the significance of findings. RESULTS: The optimal cut-off value of tumor size to predict the risk of CLNM in papillary thyroid microcarcinoma was 0.575 cm (area under the curve 0.721) according to the ROC curves. Significant differences were observed on the multifocality, extrathyroidal extension and central lymph node metastasis between two groups which were divided according to the tumor size by the cutoff values. Patients in two groups showed different positive rate and intensity of Ki67. CONCLUSIONS: The size of PTMC in ultrasound images are helpful to predict the aggressiveness of the tumors, it could be an easy predictor for PTMC prognosis and assist us to choose treatment.

[Changes in serum level of carboxy-terminal telopeptide of type I collagen in patients with coronary heart disease].

OBJECTIVE: To investigate the serum level of carboxy-terminal telopeptide of type I collagen (ICTP) and explore its correlation with MMP-2 and MMP-9 in patients with coronary artery disease (CHD). METHODS: A total of 103 CHD patients treated in our hospital between October, 2013 and May, 2014 were enrolled, including 39 with stable angina pectoris (SAP), 39 with unstable angina (UA), and 25 with acute myocardial infarction (AMI), with 38 non-CHD volunteers as the control group. The serum levels of ICTP, MMP-2, and MMP-9 were detected in all the subjects using enzyme-linked immunosorbent assay (ELISA). RESULTS: No significant difference in serum levels of MMP-2, MMP-9, or ICTP was found between the control and SAP groups or between UA and AMI groups (P>0.05), but the latter two groups had significantly higher serum levels of MMP-2, MMP-9, and ICTP than the former two groups (P<0.05). Serum ICTP level was found to negatively correlated with the fibrotic area and positively with the lipid component in the plaques (P<0.05). Regression analysis revealed significant positive correlations of serum ICTP with MMP-2 and MMP-9 (P<0.05). CONCLUSION: An elevated serum ICTP level is indicative of the presence of unstable plaques in CHD patients. Serum ICTP is more strongly correlated with MMP-2 than with MMP-9, and can be used as a non-invasive marker for assessing vulnerable plaques in patients with acute coronary syndrome.

Histones-mediated lymphocyte apoptosis during sepsis is dependent on p38 phosphorylation and mitochondrial permeability transition.

Lymphocyte apoptosis is one reason for immunoparalysis seen in sepsis, although the triggers are unknown. We hypothesized that molecules in plasma, which are up-regulated during sepsis, may be responsible for this. In this study, peripheral lymphocyte apoptosis caused by extracellular histones was confirmed both in mouse and human primary lymphocytes, in which histones induced lymphocyte apoptosis dose-dependently and time-dependently. To identify which intracellular signal pathways were activated, phosphorylation of various mitogen-activated protein kinases (MAPKs) were evaluated during this process, and p38 inhibitor (SB203580) was used to confirm the role of p38 in lymphocyte apoptosis induced by histones. To investigate the mitochondrial injury during these processes, we analyzed Bcl2 degradation and Rhodamine 123 to assess mitochondrial-membrane stability, via cyclosporin A as an inhibitor for mitochondrial permeability transition (MPT). Then, caspase 3 activation was also checked by western-blotting. We found that p38 phosphorylation, mitochondrial injury and caspase 3 activation occurred dose-dependently in histones-mediated lymphocyte apoptosis. We also observed that p38 inhibitor SB203580 decreased lymphocyte apoptotic ratio by 49% (P<0.05), and inhibition of MPT protected lymphocytes from apoptosis. Furthermore, to investigate whether histones are responsible for lymphocyte apoptosis, various concentrations of histone H4 neutralization antibodies were co-cultured with human primary lymphocytes and plasma from cecal ligation and puncture (CLP) mice or sham mice. The results showed that H4 neutralization antibody dose-dependently blocked lymphocyte apoptosis caused by septic plasma in vitro. These data demonstrate for the first time that extracellular histones, especially H4, play a vital role in lymphocyte apoptosis during sepsis which is dependent on p38 phosphorylation and mitochondrial permeability transition. Neutralizing H4 can inhibit lymphocyte apoptosis, indicating that it could be a potential target in clinical interventions for sepsis associated immunoparalysis.

[Primary non-Hodgkin lymphoma of small bowel: a clinical analysis of 34 cases].

OBJECTIVE: To study the clinical characteristics,treatment and prognosis of primary non-Hodgkin's lymphoma of small bowel. METHODS: The records of 34 patients with a confirmed diagnosis of primary non-Hodgkin's lymphoma of small bowel, registered between Jan. 1996 and Dec. 2005 at our hospital, were retrieved and analysed retrospectively. RESULTS: Twenty-seven patients had B-cell lymphoma and 7 had T-cell lymphoma of the small bowel. The major symptoms included abdominal pain and intestinal obstruction. According to Ann Arbor staging classification, 22 patients belonged to stage I~II, including 20 cases of B-cell lymphoma and 2 cases of T-cell lymphoma, and 12 patients belonged to stage III~IV, including 7 cases of B-cell lymphoma and 5 cases of T-cell lymphoma. Compared with T-cell lymphoma patients, B-cell lymphoma patients had lower lymphoma stages (P<0.05). Twenty-seven patients were treated with surgical resection. Fourteen patients were treated with six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy, and 8 patients were treated with Rituximab at the same time. T-cell lymphoma patients were more often treated with emergent operation than B-cell lymphoma patients would (P<0.05). It happened more frequently that B-cell lymphoma patients reached complete remission and their accumulative survival rate was longer than T-cell lymphoma patients did (P<0.05). CONCLUSION: Patients with stages I and II B-cell lymphoma of small bowel respond well to surgery and chemotherapy, and the treatment and prognosis of patients with T-cell lymphoma of small bowel are unsatisfactory.