Preoperative Anemia Is a Predictor of Worse Postoperative Outcomes Following Open Pancreatoduodenectomy: A Propensity Score-Based Analysis.

Background: Preoperative anemia is a common clinical situation proved to be associated with severe outcomes in major surgeries, but not in pancreatic surgery. We aim to study the impact of preoperative anemia on morbidity and mortality in patients undergoing open pancreatoduodenectomy and use propensity score matching (PSM) to balance the basal data and reduce bias. Methods: We analyzed the data of consecutive patients undergoing open pancreatoduodenectomy with a complete record of preoperative hemoglobin, at two pancreatic centers in China between 2015 and 2019. Anemia is defined as hemoglobin less than 12 g/dl for male and 11 g/dl for female, following Chinese criteria. We compared clinical and economic outcomes before and after PSM and used logistic regression analysis to assess the correlation between variables and anemia. Results: The unmatched initial cohort consisted of 517 patients. A total of 148 cases (28.6%) were diagnosed with anemia at admission, and no case received a preoperative blood transfusion or anti-anemia therapy. After PSM, there were 126 cases in each group. The rate of severe postoperative complications was significantly higher in the anemia group than in the normal group (43.7% vs. 27.0%, p = 0.006), among which the differences in prevalence of clinically relevant postoperative pancreatic fistula (CR-POPF) (31.0% vs. 15.9%, p = 0.005) and cardiac and cerebrovascular events (4.0% vs. 0.0%, p = 0.024) were the most significant. The costs involved were more in the anemia group (26958.2 ± 21671.9 vs. 20987.7 ± 10237.9 USD, p = 0.013). Among anemic patients, receiver operating characteristic (ROC) curve analysis shows the cut-off value of hemoglobin, below which, patients are prone to suffer from major complications (104.5 g/l in male and 90.5 g/l in female). Among all patients, multivariate analysis showed that preoperative obstructive jaundice [odds ratio (OR) = 1.813, 95% confidence interval (CI) (1.206-2.725), p = 0.004] and pancreatic ductal adenocarcinoma [OR = 1.861, 95% CI (1.178-2.939), p = 0.008] were predictors of anemia. Among paired patients, preoperative anemia [OR = 2.593, 95% CI (1.481-5.541), p = 0.001] and malignant pathology [OR = 4.266, 95% CI (1.597-11.395), p = 0.004] were predictors of postoperative severe complications. Conclusion: Preoperative anemia is a predictor of worse postoperative outcomes following open pancreatoduodenectomy and needs to be identified and treated.

Emerging Role of Exosomal-Derived Long Noncoding RNAs in Human PDAC.

Background: The incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) are increasing recently. Most patients with PDAC are diagnosed at advanced stage because of the high invasiveness of cancer cells and the lack of typical early symptoms. Therefore, early diagnosis of PDAC is very important to improve the prognosis. Exosomes play crucial role in intercellular communication and deliver the contents to recipient cells to regulate their biological behaviors. Recent evidence suggests emerging role of exosomes in the carcinogenesis of a variety of cancers including PDAC. Long noncoding RNAs (LncRNAs) have been reported to be involved in the development of PDAC. It has been proved that LncRNAs have the potential to be biomarkers and therapeutic targets for PDAC. Moreover, increasing number of studies focus on the role of exosomal LncRNAs in PDAC. Summary: In this review, we summarize the current status on our understanding of the role of exosomal-derived LncRNAs in the progression and metastasis of PDAC. Key Messages: We focus on challenges in the potential of exosomal-derived LncRNAs as novel diagnostic and prognostic markers and therapeutic targets of PDAC. In addition, we provide an overview about the demonstrated important role of exosomal LncRNAs in the progression of PDAC.

Fate of Surgical Patients with Small Nonfunctioning Pancreatic Neuroendocrine Tumors: An International Study Using Multi-Institutional Registries.

Several treatment guidelines for sporadic, nonmetastatic nonfunctioning neuroendocrine tumors of the pancreas (NF-pNETs) have recommended resection, however, tumors ≤ 2 cm do not necessarily need surgery. This study aims to establish a surgical treatment plan for NF-pNETs ≤ 2 cm. From 2000 to 2017, 483 patients who underwent resection for NF-pNETs ≤ 2 cm in 18 institutions from Korea and China were enrolled and their medical records were reviewed. The median age was 56 (range 16-80) years. The 10-year overall survival rate (10Y-OS) and recurrence-free survival rate (10Y-RFS) were 89.8 and 93.1%, respectively. In multivariable analysis, tumor size (>1.5 cm; HR 4.28, 95% CI 1.80-10.18, p = 0.001) and nodal metastasis (HR 3.32, 95% CI 1.29-8.50, p = 0.013) were independent adverse prognostic factors for OS. Perineural invasion (HR 4.36, 95% CI 1.48-12.87, p = 0.008) and high Ki-67 index (≥3%; HR 9.06, 95% CI 3.01-27.30, p < 0.001) were independent prognostic factors for poor RFS. NF-pNETs ≤ 2 cm showed unfavorable prognosis after resection when the tumor was larger than 1.5 cm, Ki-67 index ≥ 3%, or nodal metastasis was present. NF-pNET patients with tumors ≤ 1.5 cm can be observed if the preoperative Ki-67 index is under 3%, and if nodal metastasis is not suspected in preoperative radiologic studies. These findings support the clinical use to make decisions about small NF-pNETs.

Preoperative Nutrition Support May Reduce the Prevalence of Postoperative Pancreatic Fistula after Open Pancreaticoduodenectomy in Patients with High Nutritional Risk Determined by NRS2002.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a severe complication which may be caused by a perioperative nutrition problem. We aimed to study whether patients with high nutritional risk (NRS2002 score ≥ 5) might benefit from preoperative nutrition support regarding the risk of CR-POPF after open pancreaticoduodenectomy. METHODS: Consecutive patients undergoing open pancreaticoduodenectomy with complete record of NRS2002 at two Chinese institutions between 2013 and 2018 were analysed. CR-POPF was diagnosed following the 2016 ISGPS criteria. Nutrition support included oral nutrition supplement and enteral and parenteral nutrition. Clinical and economic outcomes were analysed. RESULTS: 522 cases were included. 135 cases (25.9%) were at high nutritional risk (NRS2002 score ≥ 5), among which 41 cases (30.4%) received preoperative nutrition support. The CR-POPF rate was significantly lower in the preoperative nutrition support group compared with the no nutrition support group (12.2% versus 28.7%, P = 0.038). Multivariate analysis showed that preoperative nutrition support was a protective factor for CR-POPF in patients at high risk [OR 0.339, 95% CI (0.115-0.965), P = 0.039]. Higher albumin and a larger diameter of the main pancreatic duct were found to be other protectors for CR-POPF. CONCLUSIONS: Patients with high nutritional risk (NRS2002 score ≥ 5) may profit from preoperative nutritional support manifested in the reduction of CR-POPF.

Retrospective analysis of 45 cases of localized retroperitoneal Castleman disease from a single center.

BACKGROUND: Castleman disease (CD) is a rare lymphoproliferative disease characterized by high heterogeneity in clinical manifestation and prognosis. This study aimed to summarize clinical features of localized retroperitoneal CD and our experiences to improve the diagnosis and treatment of this disease. METHODS: Clinical data of 45 patients with localized retroperitoneal CD were retrospectively analyzed. The differences in clinical features between groups with and without paraneoplastic pemphigus (PNP) were compared. Survival was analyzed between groups depending on whether complicating with PNP, bronchiolitis obliterans (BO), gender, age and uni-centric CD (UCD)/multi-centric CD (MCD), respectively. RESULTS: Significant differences were observed between patient groups in the prevalence of retroperitoneal CD with PNP complicated with BO (P=0.010), the constituent ratios of initial symptoms (P<0.001) and the duration from appearance of the initial symptoms to being diagnosed (P=0.009). Among 45 cases, 43 tumors had clear margins and intact envelops and were completely resected, 40 patients were cured or significantly relieved, 3 patients were not significantly relieved, 2 patients received palliative surgical therapy and eventually relapsed and died after surgery. There were significant differences in the survival rate between groups depending on complication with BO, gender and age (≤40 and >40 years) (all P<0.05). CONCLUSIONS: Prompt and complete removal of the retroperitoneal CD tumor is critical to the management of this disease, as palliative resection tends to cause relapse and lead to a poor prognosis. Retroperitoneal CD patients with PNP may develop complications from BO leading to death. Complication with PNP, complication with BO, male gender and age ≥40 years were identified as prognostic risk factors for patients with localized retroperitoneal CD.

High mobility group AT-hook 2 promotes tumorigenicity of pancreatic cancer cells via upregulating ANLN.

HMGA2 is associated with the regulation of cellular biological processes in various human disorders and cancer progression, yet little is known about how HMGA2 controls tumorigenesis. This study uncovered the mechanism of HMGA2-mediated regulation of tumorigenicity in pancreatic cancer. We showed that HMGA2 was highly expressed in pancreatic cancer cells and correlated with poor prognosis. HMGA2 expression knockdown inhibited the tumorigenicity of pancreatic cancer cells. Conversely, overexpression of HMGA2 promoted tumorigenicity. Combination of ChIP-Seq, RNA-Seq and dual-luciferase reporter assays revealed HMGA2 could directly regulate ANLN expression. Furthermore, we found ANLN could mediate the HMGA2-induced effects on pancreatic cancer cells. The identification of the regulatory mechanism of HMGA2 and ANLN will provide insights into the progression for human pancreatic cancer.

Locally advanced undifferentiated carcinoma with osteoclast-like giant cells of the pancreas.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas (UCOGCP) is an unusual pancreatic neoplasm that represents < 1% of all pancreatic malignancies. Moreover, the giant cells of UCOGCP morphologically resemble the benign giant cells of bone tumors. Due to the rarity of this tumor type, the histogenesis and biologic behavior of UCOGCP remain controversial. Here, we report a case of UCOGCP that exhibited an invasive growth pattern involving infiltration of the adjacent bowel loop and portal vein, as well as superior mesenteric vein thrombosis. The patient underwent a distal pancreatectomy with splenectomy and partial colectomy, followed by four cycles of gemcitabine chemotherapy. No evidence of recurrence was detected after ten years. In addition to this case, clinical information on other UCOGCP cases reported in the English literature is summarized.

[The diagnosis and management strategies for gastrointestinal hemorrhage following pancreaticoduodenectomy].

OBJECTIVE: To analyze the causes and clinical features of gastrointestinal hemorrhage following pancreaticoduodenectomy (PD), and to provide the management strategies for this complication. METHODS: The clinic data of 412 patients who underwent PD from January 2000 to April 2010 was retrospectively reviewed. There were 232 male and 180 female patients, average age was (60 ± 12) years. The mode of procedure was standard PD and the Child's reconstruction of digestive tract, whose anastomosic steps encluded gastroenterostomy following chlangioenterostomy and pancreaticoenterostomy, was employed. Etiology of gastrointestinal haemorrhage, diagnostic methods and treatment strategy was recorded and analyzed. RESULTS: The postoperative mobidity was 37.1% (153/412), the rate of haemorrhagic complications was 6.6% (27/412), and gastrointestinal hemorrhage was recorded in 11 patients (2.7%). The bleeding rate of pancreaticointestinal anastomosis and gastricointestinal anastomosis were 5/11 and 4/11, respectively. Among these 11 patients, early hemorrhage occurred in 6 patients, 7 patients were due to technical failure. In order to control this kind of complication, open abdominal operation alone was performed on 4 patients, endoscopic management was performed on 3 patients and succeeded in 2 patients, vascular interventional therapy was performed on 5 patients and succeeded in 2 patients, and Re-laparotomy following vascular interventional therapy was performed on 2 patients successfully. CONCLUSIONS: Gastrointestinal hemorrhage following PD always occurred in early stage and reliable hemostasis during operation is the key points for prevention. Angiography is minimally invasive and holds the diagnostic value. Timely and decisive reoperation is an important method to management of postoperative gastrointestinal hemorrhage.

[Individualized surgical treatment and prognosis of intraductal papillary mucinous neoplasms of the pancreas].

OBJECTIVE: To investigate the clinical manifestation, individualized surgical treatment, and prognosis of intraductal papillary mucinous neoplasms (IPMN) of pancreas. METHODS: The clinical data of 56 IPMN cases treated between January 2007 and December 2011 was retrospectively analyzed. Among the 56 patients (38 male and 18 female, mean age (61 ± 7) years), 26 were main-duct type, 18 were branch-duct type, 12 were mixed type. Pancreatectomy was performed on 48 cases, including pancreaticoduodenectomy on 29 patients, distal pancreatectomy on 17 patients, and total pancreatectomy on 2 patients. RESULTS: The overall postoperative morbidity rate was 27.1% (13/48), there was no perioperative mortality. Pathology showed 31 cases of noninvasive IPMN, 17 cases of invasive IPMN, and 7 cases of lymph node metastasis. The rate of invasive tumors was 46.2% (12/26) in main duct type, 3/12 in mixed type, and 2/18 in branch duct type IPMN, the difference was statistically significant (χ(2) = 6.385, P = 0.041). The five-year survival rate for patients with noninvasive and invasive neoplasms was 100% and 24.6%, respectively. The prognosis of invasive cases with lymph node metastasis was significantly worse than those without lymph node metastasis (P = 0.017). A regular follow-up without surgical treatment was performed on 8 cases with asymptomatic side branch IPMN less than 3 cm in diameter, and no progression was found during the follow-up. CONCLUSIONS: IPMN has a relative good prognosis. Main duct type and mixed type IPMN have a higher malignant potential, and should receive a surgical treatment. Patients of branch duct type IPMN with a <3 cm diameter lesion and no clinical manifestations can be managed with close follow-up only.

Hedgehog signaling pathway regulates human pancreatic cancer cell proliferation and metastasis.

Pancreatic cancer is one of the most aggressive and devastating malignancies. The Hedgehog (Hh) pathway has been reported to play an important role in pancreatic cancer development and progression. The aim of this study was to examine the activation of the Hh pathway in human pancreatic cancer tissue samples and pancreatic cancer cell lines, and the molecular mechanisms involved in the Hh pathway mediated effects on pancreatic cancer cell proliferation and invasion. The expression levels of Hh molecules in human pancreatic cancer tissue samples and pancreatic cancer cell lines were evaluated using RT-PCR. The role of the Hh pathway in cell proliferation and invasion was evaluated using flow cytometry, MTT, colony formation assays and transwell invasion assays, and the expression of cancer stem cell markers and epithelial-mesenchymal transition (EMT) were evaluated using flow cytometry and RT-PCR. Tumorigenicity assays were used to further investigate the role of the Hh pathway in vivo. Hh molecules were highly expressed in human pancreatic cancer tissue samples and pancreatic cancer cell lines. Inhibition of the Hh pathway notably decreased cell proliferation and induced apoptosis through inhibition of the PI3K/AKT pathway and cancer stem cells. Furthermore, inhibition of the Hh signaling pathway significantly inhibited EMT by suppressing the activation of transcription factors Snail and Slug, which are correlated with significantly reduced pancreatic cancer cell invasion, suggesting that the Hh signaling pathway is involved in early metastasis. These results indicate that activation of the Hh pathway is a common event. Inhibition of the Hh pathway may be a potential molecular target of new therapeutic strategies for pancreatic cancer.

[Effects and mechanisms of combined suppression of epidermal growth factor receptor and hedgehog signaling on proliferation in pancreatic cancer cells].

OBJECTIVE: To explore the synergistic effects on proliferation and apoptosis by targeted suppression of epidermal growth factor receptor (EGFR) in combination with blockade of Hedgehog signaling pathways in pancreatic cancer cells and examine the synergistic mechanism of Hedgehog and EGFR signaling pathways. METHODS: The sequences of RNA interference targeting EGFR gene were designed, synthesized and cloned into the pFU-GW-RNAi vector. And a stable transfection cell line was obtained by transfecting the human Panc-1 cells with lentivirus. The expressions of Shh and Gli1 were tested by real-time polymerase chain reaction (PCR). The antiproliferative effect was examined by the assays of colony formation and methyl thiazolyl tetrazolium (MTT). Fluorescence activated cell sorter (FACS) was applied to assay the apoptotic rate in all experimental groups. Western blot was applied to detect the phosphorylation levels of ERK and AKT.In vivo nude mice tumorigenicity model was used to test the effect of growth inhibition. RESULTS: The RNAi technology with lentivirus could restrain the expression of EGFR gene. After the blocking of EGFR and Hedgehog signaling pathways by RNAi silencing, the chemosensitivity to cyclopamine significantly increased in human pancreatic cancer cells. The half-inhibitory concentration (IC 50) of cyclopamine declined from (2.978 ± 0.336) to (1.698 ± 0.057) µmol/L (P < 0.05). The prophase apoptotic rate of co-treated group was as high as 38.75% and it was significantly higher than the RNAi silencing EGFR (17.65%) and control groups (3.02%) (P < 0.05). The results of tumor xenografts assay showed that the tumor volume of co-treated group (394.8 ± 87.5 mm(3)) was significantly lower than that of simple EGFR RNAi (594.7 ± 86.1 mm(3)) and single cyclopamine treated group (771.3 ± 82.9 mm(3)); the combination treatment could also produce obviously synergistic antiproliferative effect in colony formation assays. After RNAi silencing EGFR, the phosphorylation levels of ERK and AKT decreased significantly versus the control group. Further reduction was obtained with the combined use of cyclopamine in the co-treated group. CONCLUSION: The blocking of EGFR and Hedgehog signaling pathways by RNAi silencing may further inhibit cell proliferation and increase apoptosis in vivo and in vitro in human pancreatic cancer cells. The synergism of Hh and EGFR signaling pathways may be correlated with the phosphorylation levels of ERK and AKT.

Factors associated with post-pancreaticoduodenectomy hemorrhage: 303 consecutive cases analysis.

BACKGROUND: Because of the complexity and severity of the surgery and its associated complications, pancreaticoduodenectomy (PD) is associated with significant morbidity and mortality, especially the hemorrhage post-PD. Exploring the factors associated with post-PD hemorrhage is very important for the patients' safety. METHODS: Clinical data from 303 cases of PD between January 1998 and December 2008 were analyzed retrospectively. RESULTS: The overall mortality rate was 4.95% (15/303). However, post-operative bleeding occurred in 25 patients (8.25%) with nine episodes resulting in death (36.00%). Univariate analysis was performed and identified tumor size, Child's classification, total pancreatic uncinatic process resection, and pancreatic leakage as significant risk factors for post-PD hemorrhage. In the severe hemorrhage group, incomplete resection of uncinate process of pancreas and pancreatic leakage were the main causes. The multivariate Logistic regression analysis revealed that each of these variables is an independent risk factor. CONCLUSIONS: Primary prevention of bleeding complications depends on total pancreatic uncinatic process resection and meticulous hemostatic techniques during surgery. In addition, several peri-operative factors were found to contribute to post-PD bleeding.

Combined effects of EGFR and Hedgehog signaling pathway inhibition on the proliferation and apoptosis of pancreatic cancer cells.

In the present study, we established a new experimental model to investigate the effects of EGFR targeting by RNAi, and the synergistic actions between the hedgehog (Hh) and EGFR signaling pathways on the proliferation and apoptosis in pancreatic cancer cells. Three human pancreatic cancer cell lines expressing EGFR shRNA were established, and gene expression inhibition was assessed in these lines using RT-PCR and western blot analysis. The effects of EGFR RNAi and Hh inhibition on cell proliferation and apoptosis were explored in vitro and in vivo. We observed that EGFR RNAi notably inhibited cell proliferation and colony formation, induced apoptosis and markedly decreased xenograft tumor growth. Furthermore, EGFR RNAi significantly enhanced cyclopamine sensitivity both in vitro and in vivo, and a synergistic decrease of both AKT and ERK phosphorylation was observed. The present study demonstrates that combined inhibition of both EGFR and Hh signaling pathways could establish a more promising antitumor approach than inhibiting each singly, and that there is a possible synergistic effect for Hh and EGFR signaling pathways on ERK and AKT phosphorylation.

Influential factors and effect evaluation of the intra-operative puncture biopsy for pancreatic masses.

BACKGROUND: It 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. METHODS: A 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. RESULTS: The 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). CONCLUSIONS: Intra-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.

Suppression of the epidermal growth factor receptor inhibits epithelial-mesenchymal transition in human pancreatic cancer PANC-1 cells.

BACKGROUND: Aberrant expression of epidermal growth factor receptor (EGFR) has been detected in pancreatic cancer; however, the mechanisms of EGFR in inducing pancreatic cancer development have not been adequately elucidated. The objective of this study was to determine the role of EGFR in mediating epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. METHODS: Pancreatic cancer cell line PANC-1 was transfected with small interfering RNA of EGFR by use of a lentiviral expression vector to establish an EGFR-knockdown cell line (si-PANC-1). PANC-1 cells transfected with lentiviral vector expressing negative control sequence were used as negative control (NC-PANC-1). Scratch assay and transwell study were used to analyze cell migration and invasion. Real-time PCR and Western blotting were used to detect the expression of EMT markers E-cadherin, N-cadherin, vimentin, and fibronectin and transcription factors snail, slug, twist1, and sip1 in PANC-1, NC-PANC-1, and si-PANC-1 cells. Immunofluorescent staining with these antibodies and confocal microscopy were used to observe their cellular location and morphologic changes. RESULTS: After RNA interference of EGFR, the migration and invasion ability of si-PANC-1 cells decreased significantly. The expression of epithelial phenotype marker E-cadherin increased and the expression of mesenchymal phenotype markers N-cadherin, vimentin, and fibronectin decreased, indicating reversion of EMT. We also observed intracellular translocation of E-cadherin. Expression of transcription factors snail and slug in si-PANC-1 cells decreased significantly. CONCLUSION: Suppression of EGFR expression can significantly inhibit EMT of pancreatic cancer PANC-1 cells. The mechanism may be related with the down-regulation of the expression of transcription factors snail and slug.

[Regulatory mechanisms of Hedgehog signaling pathway for epithelial-mesenchymal transition in pancreatic cancer cells].

OBJECTIVE: To explore the blocking effects of hedgehog signaling pathway on the processes of cell migration, invasion and epithelial-mesenchymal transition (EMT) in human pancreatic cancer cells and elucidate its possible mechanisms. METHODS: The lentiviral expression vector for RNA interference of human Smoothened (SMO) gene was constructed to silence the expression of SMO. And RNAi against SMO was used to suppress the hedgehog signaling pathway in human pancreatic cancer Panc-1 cells. The in vitro invasion capacity in Panc-1 cells was assessed by Matrigel/Transwell chamber assay. Real-time PCR (polymerase chain reaction) and Western blot were used to detect the expressions of such EMT markers as E-cadherin, N-cadherin, ß-catenin, vimentin and fibronectin and such transcription factors as Snail, Slug, Twist1 and Sip1. RESULTS: The stable interference of SMO could suppress the hedgehog signaling activity in Panc-1 cells. The inhibition of hedgehog signaling reduced the in vitro invasion capacity significantly in Panc-1 cells. The expression of E-cadherin significantly increased while N-cadherin, vimentin and fibronectin were significantly down-regulated in the RNAi group. Compared to the control group, the expressions of Snail and Slug were significantly reduced in the SMO knock-down group. CONCLUSION: The inhibition of hedgehog signaling pathway reduces the in vitro invasion capacity in human pancreatic cancer cells. And the EMT process is significantly suppressed. The mechanism is partially correlated with the down-regulations of Snail and Slug.

[Surgical complications after pancreatoduodenectomy: risk factors and treatments].

OBJECTIVE: To explore the impact factors and treatment of post pancreatoduodenectomy complications. METHODS: The clinical data of 412 cases between January 1995 and April 2010 underwent pancreatoduodenectomy were analyzed retrospectively. There were 232 male, 180 female. Univariate and multivariate logistic regression model were used to identify the risk factors related to occurrence of postoperative complications. RESULTS: The overall postoperative morbidity rate was 37.1% (153/412), and mortality rate was 4.6% (19/412). Total uncinate process resection, type of pancreatic-enteric anastomosis, duct diameter and pancreatic texture had effects on postoperative pancreatic fistula statistically. Total uncinate process resection, the amount of intra-operative blood loss ≥ 600 ml and pancreatic fistula were identified as significant risk factors for post pancreatoduodenectomy hemorrhage by means of univariate analysis. Delayed gastric empting occurrence in the patients with pylorus-preserving pancreaticoduodenectomy was higher than those with standard pancreaticoduodenectomy significantly. The multivariate Logistic regression analysis revealed that duct diameter and pancreatic texture were the independent risk factors of pancreatic fistula. Total uncinate process resection, the amount of intra-operative blood loss ≥ 600 ml and pancreatic fistula were independent risk factors of bleeding. There were no statistically significant differences between the radical group and the standard group when postoperative complication rates were analyzed (P < 0.05). CONCLUSIONS: Pancreaticojejunal anastomoses by means of duct-to-mucosa is fit for the patients with dilated pancreatic duct and end-to-end invaginated pancreaticojejunostomy is fit for the patients with undilated pancreatic duct. The prevention of postoperative bleeding depends on total uncinate process resection and meticulous hemostatic technique during operation. The pancreatic fistula is one of the most important factors which can result in postoperative bleeding. Pancreaticoduodenectomy combines with SMV/PV resection and extended lymphadenectomy do not significantly increase the morbidity rates.