Ailin Wei

Preoperative biliary drainage in patients with hilar cholangiocarcinoma undergoing major hepatectomy.

AIM To investigate the effect of preoperative biliary drainage (PBD) in jaundiced patients with hilar cholangiocarcinoma (HCCA) undergoing major liver resections. METHODS An observational study was carried out by reviewing a prospectively maintained database of HCCA patients who underwent major liver resection for curative therapy from January 2002 to December 2012. Patients were divided into two groups based on whether PBD was performed: a drained group and an undrained group. Patient baseline characteristics, preoperative factors, perioperative and short-term postoperative outcomes were compared between the two groups. Risk factors for postoperative complications were also analyzed by logistic regression test with calculating OR and 95%CI. RESULTS In total, 78 jaundiced patients with HCCA underwent major liver resection: 32 had PBD prior to operation while 46 did not have PBD. The two groups were comparable with respect to age, sex, body mass index and co-morbidities. Furthermore, there was no significant difference in the total bilirubin (TBIL) levels between the drained group and the undrained group at admission (294.2 ± 135.7 vs 254.0 ± 63.5, P = 0.126). PBD significantly improved liver function, reducing not only the bilirubin levels but also other liver enzymes. The preoperative TBIL level was significantly lower in the drained group as compared to the undrained group (108.1 ± 60.6 vs 265.7 ± 69.1, P = 0.000). The rate of overall postoperative complications (53.1% vs 58.7%, P = 0.626), reoperation rate (6.3% vs 6.5%, P = 1.000), postoperative hospital stay (16.5 vs 15.0, P = 0.221) and mortality (9.4% vs 4.3%, P = 0.673) were similar between the two groups. In addition, there was no significant difference in infectious complications (40.6% vs 23.9%, P = 0.116) and noninfectious complications (31.3% vs 47.8%, P = 0.143) between the two groups. Univariate and multivariate analyses revealed that preoperative TBIL > 170 μmol/L (OR = 13.690, 95%CI: 1.275-147.028, P = 0.031), Bismuth-Corlette classification (OR = 0.013, 95%CI: 0.001-0.166, P = 0.001) and extended liver resection (OR = 14.010, 95%CI: 1.130-173.646, P = 0.040) were independent risk factors for postoperative complications. CONCLUSION Overall postoperative morbidity and mortality rates after major liver resection are not improved by PBD in HCCA patients with jaundice. Preoperative TBIL > 170 μmol/L, Bismuth-Corlette classification and extended liver resection are independent risk factors linked to postoperative complications.

Clinical outcomes of combined necrotizing pancreatitis versus extrapancreatic necrosis alone

INTRODUCTION Extrapancreatic necrosis (EPN) alone, i.e., in the absence of pancreatic parenchyma necrosis has gradually come to be regarded as a separate entity of acute necrotizing pancreatitis (ANP). However, data regarding the prognostic significance of EPN are quite limited, and the outcomes of interventions for patients with EPN alone are not well elucidated. The aim of this study was to explore the differences in the outcomes of patients with EPN alone and patients with both the pancreatic parenchyma and extrapancreatic necrosis (combined necrosis). METHODS From January 2009 to December 2013, a total of 334 patients with ANP who had received interventions in the West China Hospital in China were included. Based on the extent of necrosis as assessed with contrast-enhanced CT, the patients were divided into Group 1 (n = 285) in which the necrosis involved both the pancreatic parenchyma and extrapancreatic tissues (combined necrosis) and Group 2 (n = 49) in which the necrosis involved only the extrapancreatic tissues. Additionally, Group 3 included 443 patients with interstitial pancreatitis who were also included in the analyses. The demographic characteristics, support treatment information, organ failure information, infection necrosis, persistent systemic inflammatory response syndrome (SIRS) in the first week of onset, CT severity index, and intervention types, as well as the postoperative stay lengths, ICU utility, and complications were collected and compared. RESULTS Compared with the patients in Group 1, the patients in Group 2 suffered less persistent SIRS in the first week of onset (12/24.5% vs. 145/50.9%; P < 0.05), less persistent organ failure (6/12.2% vs. 95/33.3%; P < 0.05), less persistent multiple organ failure (3/6.1% vs. 67/23.5%; P < 0.05), and less bacteremia (5/10.2% vs. 107/37.5%; P < 0.001). The intervention types were significantly different between the two groups (P < 0.001); initial open necrosectomy was performed in 174/61.6% and 8/16.3% of the patients in Groups 1 and 2, respectively, and initial percutaneous catheter drainage (PCD) was performed in 73/25.6% and 29/59.2% of the patients in the two respective groups. Second open necrosectomies following PCD were required in 61/83.5% and 9/31.0% of the patients in Groups 1 and 2, respectively (P < 0.001). A greater number of patients in Group 1 were diagnosed with infected necrosis (204/71.6% vs. 10/20.4%; P < 0.001) and had to be sent to the ICU for further postoperative care (221/77.5% vs. 23/46.9%; P < 0.001). The postoperative stay was longer for Group 1 (median: 43.0 vs. 26.5 days; P < 0.001). Residual necrotic tissue or abscess was the most common postoperative complication in both groups. The mortality was higher in Group 1 (52/18.2% vs. 1/2.1%; P < 0.05). Compared with the patients in Group 2, the patients with interstitial pancreatitis exhibited milder courses and better outcomes. Subgroup comparisons with Group 1 indicated that early multiple organ failure was significantly associated with higher mortality. CONCLUSION The patients with EPN alone exhibited significantly better prognoses than those with combined necrosis, and EPN alone should be regarded as a separate group of acute necrotizing pancreatitis. Open necrosectomy can be avoided in the majority of patients with EPN alone, who receive PCD as the initial first intervention.

Major hepatectomy in Bismuth types I and II hilar cholangiocarcinoma

BACKGROUND Historically, hilar bile duct resection (HBDR) has been regarded as the choice of treatment for Bismuth types I and II hilar cholangiocarcinoma (HCCA). The present study aimed to evaluate the advantages of major liver resection (MLR) in the treatment of patients with Bismuth types I and II HCCA when compared with HBDR. MATERIALS AND METHODS Between January 2005 and September 2012, in total, 52 patients with Bismuth types I and II HCCA who underwent HBDR alone or MLR were included for retrospective analysis. The intraoperative outcomes, postoperative complications, and oncological outcomes including recurrence and overall or disease-free survival rate were compared. RESULTS The MLR group had significantly higher curative resection rates compared with the HBDR group (95% versus 62.5%, P = 0.021) and lower tumor recurrence (28% versus 63%, P = 0.049), albeit with longer operating time (395.5 ± 112.7 versus 270.9 ± 98.8, P < 0.001), and higher blood transfusion requirements (70% versus 16%, P < 0.001). MLR resulted in significantly higher overall postoperative morbidity (70% versus 34.4%, P = 0.012), compared with HBDR alone. When restricted to R0 resections for all the procedures, MLR significantly increased the overall postoperative survival rate compared with the HBDR group (P = 0.016); the overall survival rate at 1, 3 y was 68.4% and 60.8% for MLR group and 59.6% and 21.9% for HBDR group, respectively. Also, the disease-free survival rate was significantly higher in patients who underwent MLR, as compared with those who underwent HBDR (53.2% versus 0% at 3 y, P = 0.005). CONCLUSIONS Our study has shown that MLR results in higher curative resections, fewer recurrences, and increased postoperative survival rate for Bismuth types I and II HCCA as compared with HBDR alone. However, there is a need for well-designed, multicenter studies to be undertaken to better inform a decision on the standard treatment for Bismuth types I and II HCCA.

Deregulated expression of miR-107 inhibits metastasis of PDAC through inhibition PI3K/Akt signaling via caveolin-1 and PTEN

ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) displays a highly aggressive malignancy and is considered to be an incurable and rapidly lethal disease. MicroRNAs (miRNAs) are small non‐coding RNAs of approximately nucleotides that regulate several aspects of tumors pathogenesis, including migration, invasion, metastasis and epithelial‐mesenchymal transition. We have found that miR‐107 was significantly high expression in PDAC tissues and cells. High miR‐107 expression is associated with poor clinicopathological parameters and prognosis in PDAC patients. Deregulated expression of miR‐107 in PDAC cells (AsPC‐1 and Panc‐1) is sufficient to reduce cell migration and invasion, and to induce upregulation of epithelial markers (&bgr;‐catenin, ZO‐1 and E‐cadherin) and a decrease of mesenchymal marker expression (ZEB‐1 and vimentin). We also found that the caveolin‐1, PTEN and p‐Akt expression are modulated by miR‐107 in PDAC cells. Moreover, our study clearly demonstrated that deregulated expression of miR‐107 inhibited cell migration and invasion and EMT by up‐regulation of caveolin‐1 and PTEN, and inhibition of PI3K/Akt signaling in PDAC cells. Our study suggested that miR‐107 expression might both be a useful indicator of the metastatic potential and provided a new potential therapeutic target in PDAC.

MicroRNA-410-3p attenuates gemcitabine resistance in pancreatic ductal adenocarcinoma by inhibiting HMGB1-mediated autophagy

Gemcitabine-based chemotherapy is the most common treatment option for pancreatic ductal adenocarcinoma (PDAC). However, it offers little therapeutic value in many cases due to the rapid development of chemoresistance. MicroRNAs (miRNAs) have been found to play pivotal roles in the chemotherapeutic resistance of PDAC. We found that miR-410-3p was significantly down-regulated in human pancreatic cancer xenograft (HPCx) tumor tissues from gemcitabine-treated mice. Low miR-410-3p expression correlated with gemcitabine resistance in HPCx tumors and PDAC cells as well as poor prognosis in PDAC patients. We also found that miR-410-3p attenuated the gemcitabine resistance of PDAC by targeting the 3′-UTR of HMGB1. Moreover, our study clearly demonstrated that miR-410-3p enhanced chemosensitivity to gemcitabine via inhibiting HMGB1-induced autophagy during chemotherapy in PDAC cells. Our study suggests that miR-410-3p expression may be a useful indicator of the potential for chemoresistance to gemcitabine and provide a potential new therapeutic target for chemoresistance in PDAC.

Role of the Helix in Talin F3 Domain (F3 Helix) in Talin-Mediated Integrin Activation

Increases in ligand binding to cellular integrins (activation) play an important role in platelet and leukocyte function. Talin is necessary in vivo and sufficient in vitro for integrin αIIbβ3 activation. The precise mechanisms by which talin activates integrin are still being elucidated. In particular, talin undergoes conformational changes (around the F3 helix) and inserts the F3 helix into lipid bilayer; however, the connection between this lipid-inserting mechanism of talin and talin’s capacity to activate integrin has never been explored before. In this work, we used rational mutagenesis, modeled cell systems, and structural modeling to study the potential role of membrane-induced talin conformational changes in talin-mediated integrin activation. Mutations of the residues critical for talin F3 helix to insert into membrane completely abolished talin-mediated integrin activation without affecting the binding of talin to integrins. Furthermore, mutations of the lipid-binding sequences in talin F3 helix significantly reduced the capacity of talin to activate integrin. Our results suggest that the F3 helix may contribute to talin-mediated integrin activation.

Early complications after interventions in patients with acute pancreatitis.

AIM To identify the possible predictors of early complications after the initial intervention in acute necrotizing pancreatitis. METHODS We collected the medical records of 334 patients with acute necrotizing pancreatitis who received initial intervention in our center. Complications associated with predictors were analyzed. RESULTS The postoperative mortality rate was 16% (53/334). Up to 31% of patients were successfully treated with percutaneous catheter drainage alone. The rates of intra-abdominal bleeding, colonic fistula, and progressive infection were 15% (50/334), 20% (68/334), and 26% (87/334), respectively. Multivariate analysis indicated that Marshall score upon admission, multiple organ failure, preoperative respiratory infection, and sepsis were the predictors of postoperative progressive infection (P < 0.05). Single organ failure, systemic inflammatory response syndrome upon admission, and C-reactive protein level upon admission were the risk factors of postoperative colonic fistula (P < 0.05). Moreover, preoperative Marshall score, organ failure, sepsis, and preoperative systemic inflammatory response syndrome were the risk factors of postoperative intra-abdominal bleeding (P < 0.05). CONCLUSION Marshall score, organ failures, preoperative respiratory infection, sepsis, preoperative systemic inflammatory response syndrome, and C-reactive protein level upon admission are associated with postoperative complications.

Differential Binding of Active and Inactive Integrin to Talin

Bi-directional signaling of integrins plays an important role in platelet and leukocyte function. Talin plays a key role in integrin bi-directional signaling and its binding to integrin is highly regulated. The precise regulation of the recruitment and binding of talin to integrin is still being elucidated. In particular, the recruitment of talin to integrin is controlled by the RAP-1 and RIAM/lamellipodin signaling axis and the affinity between talin and integrin is regulated by the conformation or protease cleavage of talin. However, whether the binding between integrin and talin is also regulated by integrin conformation has not been thoroughly explored before. In this work, we used biochemical binding assays to study the potential role of integrin conformational changes in integrin–talin interactions. Constitutively active integrin αIIbb3 binds markedly stronger to talin than inactive αIIbb3. Inactive αIIbb3 markedly increases its binding to talin once activated, regardless of how αIIbb3 is activated. Further, the increased binding to talin is b3 tail dependent. Our results suggest that integrin conformation is another regulatory mechanism for integrin–talin interaction.

Laparoscopic Splenectomy for the Elderly Liver Cirrhotic Patients With Hypersplenism: A Retrospective Comparable Study.

AbstractA growing body of evidence has supported the benefits of laparoscopic splenectomy (LS) for hypersplenism due to liver cirrhosis. With the increased proportion of elderly persons worldwide, it is necessary to investigate the risks and benefits of LS in elderly liver cirrhotic patients.From September 2003 to March 2012, LS and open splenectomy (OS) were performed for 21 (Group 1) and 19 (Group 3) patients, respectively, all of whom were 65 years of age and older; in addition, 39 patients who were <65 years old were treated with LS and referred to as Group 2. Data (i.e., demographic characteristics and preoperative, intraoperative, and postoperative information) were retrospectively collected. Between-group comparisons were performed for the above-mentioned data.Compared with the patients in Group 3, the patients in Group 1 required longer operative times, fewer transfusions, less intensive care, a shorter postoperative course, and a shorter time to the first oral intake, and they had less blood loss and fewer postoperative short-term complications. During the follow-up period, compared with the preoperative status, significant changes in hemoglobin, leukocyte, platelet, and albumin levels were observed in all groups, whereas changes in the total BILirubin (BIL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were inconspicuous.Patients >65 years of age with hypersplenism caused by liver cirrhosis can safely undergo LS.