Activation of CRF/CRFR1 Signaling in the Central Nucleus of the Amygdala Contributes to Chronic Stress-Induced Exacerbation of Neuropathic Pain by Enhancing GluN2B-NMDA Receptor-Mediated Synaptic Plasticity in Adult Male Rats.

Exacerbation of pain by chronic stress and comorbidity of pain with stress-related disorders such as depression and post-traumatic stress disorder, represent significant clinical challenges. Previously we have documented that chronic forced swim (FS) stress exacerbates neuropathic pain in spared nerve injury (SNI) rats, associated with an up-regulation of GluN2B-containing N-methyl-D-aspartate receptors (GluN2B-NMDARs) in the central nucleus of the amygdala (CeA). However, the molecular mechanisms underlying chronic FS stress (CFSS)-mediated exacerbation of pain sensitivity in SNI rats still remain unclear. In this study, we demonstrated that exposure of CFSS to rats activated the corticotropin-releasing factor (CRF)/CRF receptor type 1 (CRFR1) signaling in the CeA, which was shown to be necessary for CFSS-induced depressive-like symptoms in stressed rats, and as well, for CFSS-induced exacerbation of pain hypersensitivity in SNI rats exposed to chronic FS stress. Furthermore, we discovered that activation of CRF/CRFR1 signaling in the CeA upregulated the phosphorylation of GluN2B-NMDARs at tyrosine 1472 (pGluN2BY1472) in the synaptosomal fraction of CeA, which is highly correlated to the enhancement of synaptic GluN2B-NMDARs expression that has been observed in the CeA in CFSS-treated SNI rats. In addition, we revealed that activation of CRF/CRFR1 signaling in the CeA facilitated the CFSS-induced reinforcement of long-term potentiation as well as the enhancement of NMDAR-mediated excitatory postsynaptic currents in the basolateral amygdala (BLA)-CeA pathway in SNI rats. These findings suggest that activation of CRF/CRFR1 signaling in the CeA contributes to chronic stress-induced exacerbation of neuropathic pain by enhancing GluN2B-NMDAR-mediated synaptic plasticity in rats subjected to nerve injury. PERSPECTIVE: Our present study provides a novel mechanism for elucidating stress-induced hyperalgesia and highlights that the CRF/CRFR1 signaling and the GluN2B-NMDAR-mediated synaptic plasticity in the CeA may be important as potential therapeutic targets for chronic stress-induced pain exacerbation in human neuropathic pain. DATA AVAILABILITY: The data that support the findings of this study are available from the corresponding author upon reasonable request.

[Effect of Circulating Plasma Cells on the Prognosis of Patients with Multiple Myeloma].

OBJECTIVE: to analyze the effect of circulating plasma cells(CPC) on the prognosis of patients with multiple myeloma(MM) in the era of new drugs, and to explore the new definition standard of primary plasma cell leukemia(pPCL). METHODS: The clinical data of 321 patients with newly diagnosed MM and 21 patients with pPCL admitted to our hospital from January 2014 to May 2022 were retrospectively analyzed. According to the proportion of CPC in peripheral blood smears, all patients were divided into 4 groups: CPC 0% group(211 cases), CPC 1%-4% group(69 cases), CPC 5%-19% group(41 cases) and CPC≥20% group(21 cases). The clinical features of patients in each group were compared and the prognosis fators was analyzed. RESULTS: The median OS of the four groups were 44.5,21.3,24.6 and 12.8 months, respectively. Among them, 295 patients(86.3%) were treated with new drugs, and the median OS of the four groups were not reached, 26.7, 24.6 and 14.9 months, respectively. As the survival curves of CPC 5%-19% group and CPC≥20% group were similar, the patients were divided into CPC<5% group and CPC≥5% group, the median OS of CPC<5% group was better than that in CPC≥5% (43.5 vs 22.3 months, P<0.001). In addition, the median OS of patients in the CPC 1%-4% group was also significantly lower than that in the CPC 0% group and similar to that in the CPC≥5% group. Multivariate analysis showed that 1%-4% CPC was an independent risk factor for the OS of patients with CPC<5%. The patients with CPC<5% were stratified by R-ISS staging, and the OS of R-ISS stage Ⅰ or stage Ⅱ with 1%-4% CPC was similar to that of R-ISS stage Ⅲ. The newly defined pPCL patients showed increased tumor load and obvious invasive characteristics. Multivariate analysis showed no independent prognostic factors for pPCL, and high-risk cytogenetic abnormalities(HRCA) had no significant effect on the prognosis. CONCLUSION: The validity of IMWG's new pPCL definition standard was verified, and it was found that the survival of MM with 1%-4% CPC also is poor and the prognosis is very close to pPCL. In addition, the newly defined pPCL has unique clinical and biological characteristics.

[Correlation between D-Dimer/Fibrinogen Ratio and Bleeding in Patients with Newly Diagnosed Acute Promyelocytic Leukemia].

OBJECTIVE: To further explore the better indicators for predicting the degree of bleeding associated with newly diagnosed acute promyelocytic leukemia (APL). METHODS: A total of 131 patients with newly diagnosed APL were classified according to WHO bleeding scales before treatment and divided into two groups: scales 0, 1 and 2 were included in no severe bleeding group, scales 3 and 4 were included in severe bleeding group. The information of the patients were collected, including sex, age, hemoglobin (Hb), white blood cell (WBC) count and platelet (PLT) count, peripheral blood lymphocyte percentage (LYMPH%), peripheral blood monocyte percentage (MONO%), percentage of leukemic cells in pripheral blood and bone marrow, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) levels, D-dimer (D-D), D-dimer/fibrinogen ratio (DFR). RESULTS: Among 131 patients, 110 were classified as no severe bleeding, and 21 were severe bleeding. The results of univariate analysis showed that patients with severe bleeding had significantly higher percentage of leukemic cells in pripheral blood, WBC, D-D, and DFR, as well as longer PT and lower LYMPH%, compared to those with no severe bleeding. Multivariate analysis revealed that DFR (OR =1.054, 95%CI : 1.024-1.084, P < 0.001) and percentage of peripheral blood leukemic cells (OR=1.026, 95%CI: 1.002-1.051, P =0.033) were independent risk factors for severe bleeding. The area under ROC curve (AUC) of peripheral blood leukemic cells, D-D and DFR were 0.748, 0.736 and 0.809, respectively. There was no statistical difference between the peripheral blood leukemic cells and D-D in diagnostic efficacy (P =0.8708). Compared with D-D, DFR had a higher predictive value (P =0.0302). The optimal cut-off value of DFR was 16.50, with a sensitivity of 90.5% and a specificity of 70.0%. CONCLUSION: DFR has a significant advantage in predicting the degree of bleeding associated with newly diagnosed APL. The greater the DFR value, the heavier the degree of bleeding. The risk of severe or fatal bleeding increases when DFR is greater than 16.50.

AQP4 Aggravates Cognitive Impairment in Sepsis-Associated Encephalopathy through Inhibiting Nav 1.6-Mediated Astrocyte Autophagy.

The pathology of sepsis-associated encephalopathy (SAE) is related to astrocyte-inflammation associated with aquaporin-4 (AQP4). The aim here is to investigate the effects of AQP4 associated with SAE and reveal its underlying mechanism causing cognitive impairment. The in vivo experimental results reveal that AQP4 in peripheral blood of patients with SAE is up-regulated, also the cortical and hippocampal tissue of cecal ligation and perforation (CLP) mouse brain has significant rise in AQP4. Furthermore, the data suggest that AQP4 deletion could attenuate learning and memory impairment, attributing to activation of astrocytic autophagy, inactivation of astrocyte and downregulate the expression of proinflammatory cytokines induced by CLP or lipopolysaccharide (LPS). Furthermore, the activation effect of AQP4 knockout on CLP or LPS-induced PPAR-γ inhibiting in astrocyte is related to intracellular Ca2+ level and sodium channel activity. Learning and memory impairment in SAE mouse model are attenuated by AQP4 knockout through activating autophagy, inhibiting neuroinflammation leading to neuroprotection via down-regulation of Nav 1.6 channels in the astrocytes. This results in the reduction of Ca2+ accumulation in the cell cytosol furthermore activating the inhibition of PPAR-γ signal transduction pathway in astrocytes.

Impairment of antigen-presenting function of peripheral γδ T cells in patients with sepsis.

Impairment of antigen-presenting functions is a key mechanism contributing to sepsis-induced immunosuppression. Recently, γδ T cells have been demonstrated as professional antigen-presenting cells (APCs); however, their role in sepsis remains unknown. In this in vitro study, the APC function of human peripheral γδ T cells was assessed using samples collected from 42 patients with sepsis and 27 age-matched healthy controls. The APC-related markers HLA-DR, CD27, CD80, and CCR7 on fresh γδT cells were significantly higher in patients with sepsis compared with matched controls; however, they responded poorly to 4-hydroxy-3-methyl-2-butenyl pyrophosphate (HMBPP) stimulation, characterized by the deactivation of these APC markers and impaired proliferation. Furthermore, the adhesion function of γδ T cells, essential for antigen presentation, was greatly reduced in patients with sepsis; for instance, in co-cultures with green fluorescent protein-expressing Escherichia coli, HMBPP-activated γδT cells from healthy individuals adhered to E. coli efficiently, whereas no such phenomenon was observed with respect to γδT cells from patients with sepsis. In line with these results, in co-cultures with isolated CD4+ αß T cells, HMBPP-activated γδT cells of healthy individuals promoted the efficient proliferation of CD4+ αß T cells, whereas γδT cells from patients with sepsis did not do so. In conclusion, our findings show that the antigen-presenting function of γδT cells is severely impaired in patients with sepsis and the mechanisms behind need further study.

Correction to: Exosomal miR-21 regulates the TETs/PTENp1/PTEN pathway to promote hepatocellular carcinoma growth.

Following the publication of article [1], the authors found that the images of Transwell Matrigel invasion (Fig. 7d) are incorrect.

Exosomal miR-21 regulates the TETs/PTENp1/PTEN pathway to promote hepatocellular carcinoma growth.

BACKGROUND: As an important means of communication, exosomes play an important role in the development of hepatocellular carcinoma (HCC). METHODS: Bioinformatics analysis, dual-luciferase reporter assays, methylation-specific quantitative PCR, and ChIP-PCR analysis were used to gain insight into the underlying mechanism of miR-21 in HCC. RESULTS: The detection of miRNAs in exosomes of HCC showed that miR-21 expression in exosomes was positively correlated with the expression level of miR-21 in cells and negatively correlated with the expression of its target genes PTEN, PTENp1 and TETs. HCC cell-derived exosomes could increase miR-21 and p-Akt expression in HCC cells and downregulate the expression of PTEN, PTENp1 and TETs. MiR-21 inhibitors or PTENp1 overexpression vectors could weaken the effect of the abovementioned exosomes and simultaneously weaken their role in promoting cell proliferation and migration and inhibiting apoptosis. Further studies showed that miR-21 not only directly regulated the expression of PTEN, PTENp1 and TETs but also increased the methylation level of the PTENp1 promoter by regulating the expression of TETs, thereby inhibiting the expression of PTENp1 and further downregulating the expression of PTEN. CONCLUSIONS: Exosomal miR-21 can regulate the expression of the tumor suppressor genes PTEN and PTENp1 in various ways and affect the growth of HCC cells.

A comparative analysis of genetic diversity of candidate genes associated with type 2 diabetes in worldwide populations.

Over the last decade, a larger number of type 2 diabetes mellitus (T2DM) susceptible candidate genes have been reported by numerous genome-wide association studies (GWAS). Understanding the genetic diversity of these candidate genes among worldwide populations not only facilitates to elucidating the genetic mechanism of T2DM, but also provides guidance to further studies of pathogenesis of T2DM in any certain population. In this study, we identified 170 genes or genomic regions associated with T2DM by searching the GWAS databases and related literatures. We next analyzed the genetic diversity of these genes (or genomic regions) among present-day human populations by curetting the 1000 Genomes Projects phase1 dataset covering 14 worldwide populations. We further compared the characteristics of T2DM genes in different populations. No significant differences of genetic diversity were observed among the 14 worldwide populations between the T2DM candidate genes and the non-T2DM genes in terms of overall pattern. However, we observed some genes, such as IL20RA, RNMTL1-NXN, NOTCH2, ADRA2A-BTBD7P2, TBC1D4, RBM38-HMGB1P1, UBE2E2, and PPARD, show considerable differentiation between populations. In particular, IL20RA (FST=0.1521) displays the greatest population difference which is mainly contributed by that between Africans and non-Africans. Moreover, we revealed genetic differences between East Asians and Europeans on some candidate genes such as DGKB-AGMO (FST=0.173) and JAZF1 (FST=0.182). Our results indicate that some T2DM susceptible candidate genes harbor highly-differentiated variants between populations. These analyses, despite preliminary, should advance our understanding of the population difference of susceptibility to T2DM and provide insightful reference that future studies can relay on.

Activation of peroxisome proliferator-activated receptor-γ (PPARγ) inhibits hepatoma cell growth via downregulation of SEPT2 expression.

Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis and low therapeutic efficacy. Recent studies have demonstrated the therapeutic prospect of peroxisome proliferator-activated receptor-γ (PPARγ) cancer angiogenesis. However, the action mechanisms remain elusive. In the present study, by using mass spectrometry, we found that PPARγ ligand rosiglitazone (RGZ) could regulate HCC cell growth by influencing various downstream factors and pathways. Among the altered proteins, septin 2 (SEPT2) was found to exhibit oncogenic function. PPARγ overexpression could inhibit the expression of SEPT2, thus blocking the promoting effects of SEPT2 on HCC cell proliferation, invasion and its inhibitory effect on cell apoptosis. Further studies also indicated that SEPT2 promoted HCC cell growth via upregulation of matrix metalloproteinase (MMP)-2 and -9, and simultaneously inhibited the cleavage of caspase-3, -7, and -9. Interestingly, the effects of SEPT2 on the above factors could be suppressed by PPARγ overexpression, suggesting that PPARγ could inhibit HCC cell growth via regulating the expression and blocking the oncogenic function of SEPT2. Taken together, these results provide new evidence for the action mechanisms of PPARγ in carcinogenesis of HCC, and upon further investigation, PPARγ could be developed as a new target for the treatment of liver cancer.

Gli2 silencing enhances TRAIL-induced apoptosis and reduces tumor growth in human hepatoma cells in vivo.

Our previous studies have showed that Gli2 played a predominant role in proliferation and apoptosis resistance to TRAIL in hepatoma cells. The purpose of this study was to explore whether Gli2 silencing enhances efficiency of TRAIL for hepatoma in vivo. SMMC-7721-shRNA cells were implanted subcutaneously into nude mices and TRAIL was injected into the peritoneal space. TUNEL assay was used to detect apoptosis of tumor cells. The expression of Gli2, c-FLIPL, c-FLIPS, and Bcl-2 protein was determined by immunohistochemistry, respectively. Apoptosis and the level of caspases proteins in SMMC-7721 and HepG2 cells were detected by Flow cytometry and Western blot. Transcriptional activity of c-FLIP induced by Gli2 was measured by luciferase reporter gene assay. The results showed that lower volumes and weights of tumor were found in mice xenografted with SMMC-7721-shRNA cells as compared with control cells in the presence of TRAIL (P < 0.05). TUNEL assay showed significantly higher apoptosis index (AI) in the SMMC-7721-shRNA group than in the control groups (P < 0.05). There were remarkable positive correlations between Gli2 and c-FLIPL, c-FLIPS, Bcl-2 protein expression. Over-expression of c-FLIP or Bcl-2 in HepG2 cells attenuated TRAIL-induced apoptosis via suppression of caspase-8 or caspase-9 activity, respectively. Luciferase reporter gene assay found a regulatory sequence by which Gli2 activated transcription between -1007 to -244 in the c-FLIP promoter region. This study demonstrates that Gli2 showed regulatory activity on transcription of c-FLIP gene, and Gli2 silencing enhances TRAIL-induced apoptosis via down-regulation of c-FLIP and Bcl-2 in human hepatoma cells in vivo.

MicroRNA-1269 promotes proliferation in human hepatocellular carcinoma via downregulation of FOXO1.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies and a major cause of cancer-related mortality in the world. MicroRNAs (miRNAs) are small, noncoding RNAs that play essential roles in various stages during cancer progression. The aim of the current study was to elucidate the role of miR-1269 in the pathogenesis of HCC. METHODS: The expression of miR-1269 in HCC cells and tissues were determined by Real-time PCR analysis. Cell viability, colony formation and anchorage-independent growth ability assays were performed to examine cell proliferative capacity and tumorigenicity. Flow cytometry analysis was conducted to determine cell cycle progression. The expression of p21, CyclinD1, phosphorylated Rb, Rb and FOXO1 were examined by Western blotting analysis. Luciferase assay was used to determine whether FOXO1 is the direct target of miR-1269. RESULTS: miR-1269 was upregulated in HCC cells and tissues. Ectopic miR-1269 expression promoted, but inhibition of miR-1269 reduced, proliferation, tumorigenicity and cell cycle progression of HCC cells. Furthermore, we demonstrated that FOXO1 was a direct target of miR-1269. Suppression of FOXO1 by miR-1269 was associated with dysregulation of p21, cyclin D1, phosphorylated Rb and Ki67 expression, thereby playing an essential role in the growth of HCC cells. CONCLUSIONS: Our study indicated that overexpression of miR-1269 promotes cell proliferation in HCC through directly suppressing FOXO1, and functions as an oncomiR in HCC.

miR-145 suppresses cell invasion in hepatocellular carcinoma cells: miR-145 targets ADAM17.

AIM: miR-145 is a candidate tumor suppressor miRNA. However, it is unknown whether miR-145 is involved in the invasion of hepatocellular carcinoma (HCC). Therefore, we aimed to explore the effect and mechanism of miR-145 in the control of HCC cell invasion. METHODS: HCC cell invasion was evaluated by transwell assays after transfection with pre-miR-145 or anti-miR-145. A luciferase reporter assay was used to determine whether a disintegrin and metalloprotease 17 (ADAM17) were a target of miR-145. The levels of miR-145 and ADAM17 mRNA were detected by a real-time polymerase chain reaction assay, and the level of ADAM17 protein was measured by western blot analysis. Pearson's correlation test was used to assess the correlation between ADAM17 mRNA expression and miR-145 expression in 20 HCC tissue samples. RESULTS: miR-145 was significantly downregulated in HCC tissues and cell lines. The loss of miR-145 expression was associated with the tumor-node-metastasis stage, vascular invasion and intrahepatic metastasis. The overexpression of miR-145 was able to suppress tumor MHCC-97H cell invasion, whereas the knockdown of miR-145 expression induced SMMC-7721 cell invasion. We demonstrated that miR-145 bound directly to the 3'-untranslated region of ADAM17 and inhibited the expression of ADAM17. The knockdown of ADAM17 in SMMC-7721 cells could partially reverse the effects of anti-miR-145. miR-145 expression was inversely associated with ADAM17 expression in 20 HCC tissue specimens. CONCLUSION: Our findings indicate that miR-145 could inhibit HCC cell invasion by regulating the expression of ADAM17.

[Transforming growth factor ß1 cooperates with stromal cell derived factor 1 to affect the proliferation of hepatic oval cells via ß-catenin inactivation].

OBJECTIVE: To investigate the role of stromal cell derived factor 1 (SDF-1) on the proliferation of hepatic oval cells, and the influencing factors. METHODS: Flow cytometry was used to detect the expression of CXCR4 on the cell surface when WB-F344 cells were growing in the culture medium with and without transforming growth factor ß1 (TGF-ß1) respectively. Western bolt was used to detect the expression of ß-catenin and its phosphorylation level. The translocation of ß-catenin was shown by confocal microscopy analysis. Q-RT-PCR was used in detecting the ß-catenin downstream gene expression such as Ccnd1 and c-Myc. MTT was used to detect the proliferation of WB-F344 cells which were treated by SDF-1 + TGF-ß1 and those cells exposed to SDF-1 or TGF-ß1 only, as well as of the negative control group. RESULT: WB-F344 cells rarely express CXCR4 under conventional circumstance, but this receptor can be up-regulated when the culture medium contain a modest amount of TGF-ß1 (the rate of CXCR4 positive cell increased by 39.5%). The bond of SDF-1 to CXCR4 results in the phosphorylation of ß-catenin, and its inactivation. SDF-1 alone didn't affect the proliferation of WB-F344 cells (0.512 ± 0.010 vs. 0.513 ± 0.008, t = 0.337, P > 0.05), while TGF-ß1 group show a slight decrease of cell population (0.393 ± 0.007,t = 28.001, P < 0.05). But when TGF-ß1 combined with SDF-1, the proliferation of WB-F344 was more weakened than TGF-ß1 group, and the difference was statistically significant (0.272 ± 0.009,t = 32.204, P < 0.05). CONCLUSIONS: TGF-ß1 can up-regulate the expression of CXCR4 in hepatic oval cells, and then inhibit the proliferation of hepatic oval cells via inactivating ß-catenin in vitro.

Green tea polyphenol epigallocatechin-3-gallate enhances 5-fluorouracil-induced cell growth inhibition of hepatocellular carcinoma cells.

AIM: 5-Fluorouracil (5-FU) is one of the most commonly used chemotherapeutic drugs. Resistance to 5-FU is a major cause of chemotherapy failure in advanced-stage hepatocellular carcinoma (HCC). Green tea polyphenol Epigallocatechin-3-gallate (EGCG) plays a critical role in growth inhibition and apoptotic induction in HCC cell lines. The aim of this study is to investigate whether EGCG can enhance 5-FU-induced cell growth inhibition and to explore its potential mechanisms. METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cell growth. Western blotting analysis was performed to detect the proteins expression in Hep3B cells. Small interfering RNA was used to suppress cyclooxygenase-2 (COX-2) expression. Furthermore, enzyme linked immunosorbent assay was used to test the prostaglandin E(2) (PGE(2) ) production in cell cultures. RESULTS: Epigallocatechin-3-gallate augmented the anti-tumor effect of 5-FU in Hep3B cells. Significant difference was observed between the treated groups and the control group (P < 0.05). EGCG (its concentrations at over 5 µmol/L) combined with 5-FU presented a synergic effect. Furthermore, the combination of EGCG and 5-FU abrogated the COX-2 overexpression and PGE(2) secretion induced by 5-FU. The upregulation of COX-2 expression decreased the phosphorylation of Akt (Thr(308) ) expression. These appeared to be followed by the AMPK hyperactivation. CONCLUSION: Epigallocatechin-3-gallate sensitizes HCC cells to 5-FU antitumor activity, and the combination of EGCG and 5-FU exhibits synergism in chemo-resistant cancer cells. The results suggest potential novel therapies for the treatment of advanced-stage liver cancer.

[Effects of E-selectin and their ligands on the adhesive metastasis of hepatocellular carcinoma].

OBJECTIVES: To explore the effects of E-selectin, ICAM-1 and their ligands on the adhesive metastasis of hepatocellular carcinoma (HCC), and to select possible anti-adhesion drugs for hepatocellular carcinoma metastasis. METHODS: 78 HCC patients were analyzed with the correlation of clinical features to the expression levels of E-selectin, sLeX, sLeA and CD44v6 in the tumor tissue. The adhesion between HepG2 and endothelial cell lines was examined by solid phase adhesion assay in vitro. Two kinds of drugs were accessed for their anti-adhesion ability. RESULTS: The positive rate of E-selectin in vascular endothelia cells adjacent to cancer nest is 70.51%, and which of sLeX, sLeA, CD44v6 within tumor cells is 64.10%, 69.23%, 62.90% respectively. The patients' life span is closely related with the positive expression of sLeX, sLeA, CD44v6 (P = 0.008, 0.001, 0.022). The positive expression of E-selectin, sLeX and sLeA is significantly correlated to portal vein tumor thrombus (PVTT), preoperative extrahepatic metastasis, and satellite foci, but not to the size of tumor and AFP. The level of CD44v6 expression is significantly correlated to patient's survival time. The expression levels of E-selectin and ICAM-1 are remarkably higher after ED25 and ECV304 cell lines be activated. Meanwhile the adhesive ability of HepG2 to endothelial cell is mediated. Dexamethasone, tanshinone IIA are able to block this adhesion at low concentration. CONCLUSION: The expression levels of E-selectin, sLeX, sLeA and CD44v6 are closely correlated with clinical features. E-selectin, ICAM-1 and their ligands are important molecules of hepatocellular carcinoma and endothelial cells to tumor adhesive metastasis. Dexamethasone, tanshinone II A can be hopefully used as anti-adhesion drugs.

[Risk factors of postoperative complications of pancreatoduodenectomy].

BACKGROUND & OBJECTIVE: Pancreatoduodenectomy is the main treatment for pancreatic carcinoma and periampullary carcinoma. This study was to explore risk factors of postoperative complications of pancreatoduodenectomy for pancreatic carcinoma and periampullary carcinoma. METHODS: Clinical data of 94 patients with pancreatic carcinoma or periampullary carcinoma, underwent pancreatoduodenectomy at the second affiliated hospital of Guangzhou Medical Collage and Gansu Provincial Tumor Hospital from Jan. 1993 to Nov. 2006, were analyzed. Thirteen clinicopathologic factors that could possibly influence postoperative mortality and morbidity were selected for univariate analysis and multivariate analysis using Cox proportional hazards model. RESULTS: Univariate analysis showed that major risk factors of postoperative mortality and morbidity of the patients were total serum bilirubin level, serum album level, duration of jaundice, decompression of jaundice, operating time, intra-operative bleeding, and depth of tumor invasion (P<0.05). Multivariate analysis showed that intra-operative bleeding, operating time, total serum bilirubin level, and duration of jaundice were independent risk factors (P<0.01). CONCLUSION: Postoperative mortality and morbidity of pancreatoduodenectomy for periampullary carcinoma are closely related to intra-operative bleeding, operating time, serum bilirubin level and duration of jaundice.