[The Efficacy of 17 Cases of Pancreaticoduodenectomy Combined with Vascular Resection and Reconstruction by Using Robotic Operation System (with Video)].

OBJECTIVE: To explore the clinical efficacy of pancreaticoduodenectomy (PD) combined with vascular resection and reconstruction under robotic surgery system in the treatment of borderline resectable pancreatic cancer. METHODS: The clinical data of 17 patients with borderline resectable pancreatic cancer who underwent PD combined with vascular resection and reconstruction (see the Video 1 in Supplemental Contents, http://ykxb.scu.edu.cn/article/doi/10.12182/20200760202) under robotic surgery system between August 2011 and September 2018 was analyzed retrospectively. RESULTS: There were 4 cases required conversion because of serious tumor invasion and soft pancreas texture, the other 13 cases were successfully completed. 16 cases (94%) achieved margin-negative resection (R0 resection), 14 cases combined with vein resection, and 3 cases combined with arterial resection. The mean operation time was (401±170) min, the mean blood loss was (647±345) mL, the mean postoperative length of hospital stay was (20±8) d. There was no perioperative death. Postoperative pathology findings and follow-up outcomes were as follows: 1 patient was diagnosed as intraductal papillary mucinous neoplasm (IPMN) and 1 patient was diagnosed as pancreatic neuroendocrine tumors (PNET) (Grade 1), 8 patients with pancreatic ductal adenocarcinoma (PDAC). 1 patient with pancreatic neuroendocrine carcinoma (PNEC) died because of tumor recurrence and metastasis during the follow-up period, the median (Min-Max) survival time was 12 (8-26) months. 5 patients with PDAC and 1 patient with malignant IPMN were currently in the follow-up period. CONCLUSION: It is safe and feasible to perform RPD with vascular resection and reconstruction. The patient's condition should be fully evaluated before surgery to select the most appropriate treatment.

Robotic pancreatectomy for solid pseudopapillary tumors in the pancreatic head: A propensity score-matched comparison and analysis from a single center.

BACKGROUND: Robotic surgery is the most advanced minimally invasive technique for the treatment of complicated solid pseudopapillary tumors (SPT). The aim of this study is to evaluate feasibility of robotic surgery for the treatment of SPTs in the pancreatic head. METHODS: A retrospective analysis of the clinical data of 83 SPTs in pancreatic head was conducted. Clinical characteristics were extracted and propensity score matching (PSM) was used to compare and evaluate mid-term outcomes of the two techniques. RESULTS: Pancreaticoduodenectomy (PD), duodenum-preserving partial pancreatic head resection (DPPHR-P) and tumor enucleation (En) were performed in 51, 24, and 8 patients, respectively. The robotic approach was associated with a significantly lower volume of blood loss, lower need for transfusion, and faster time to post-surgery recovery. Major complications and costs were comparable for both techniques. CONCLUSION: A robotic approach provides an alternative to open surgery for SPTs in the pancreatic head without increasing the incidence of clinically relevant pancreatic fistula (CRPF) or other major complications and with good patient outcomes.

An allosteric PGAM1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma.

Glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by coordinating glycolysis and biosynthesis. A well-validated PGAM1 inhibitor, however, has not been reported for treating pancreatic ductal adenocarcinoma (PDAC), which is one of the deadliest malignancies worldwide. By uncovering the elevated PGAM1 expressions were statistically related to worse prognosis of PDAC in a cohort of 50 patients, we developed a series of allosteric PGAM1 inhibitors by structure-guided optimization. The compound KH3 significantly suppressed proliferation of various PDAC cells by down-regulating the levels of glycolysis and mitochondrial respiration in correlation with PGAM1 expression. Similar to PGAM1 depletion, KH3 dramatically hampered the canonic pathways highly involved in cancer metabolism and development. Additionally, we observed the shared expression profiles of several signature pathways at 12 h after treatment in multiple PDAC primary cells of which the matched patient-derived xenograft (PDX) models responded similarly to KH3 in the 2 wk treatment. The better responses to KH3 in PDXs were associated with higher expression of PGAM1 and longer/stronger suppressions of cancer metabolic pathways. Taken together, our findings demonstrate a strategy of targeting cancer metabolism by PGAM1 inhibition in PDAC. Also, this work provided "proof of concept" for the potential application of metabolic treatment in clinical practice.

Silencing of long noncoding RNA LINC00958 prevents tumor initiation of pancreatic cancer by acting as a sponge of microRNA-330-5p to down-regulate PAX8.

Pancreatic cancer (PC) represents a relatively rare but severe malignancy worldwide. Accumulated studies have emphasized the potential of long noncoding RNA (lncRNA) as therapeutic strategies for several human cancers. Thus, we aimed to investigate whether a novel non-coding RNA regulatory circuitry involved in PC. Aberrantly expressed lncRNAs and mRNAs were screened out of microarray database. Following the determination of RNA expression, PANC-1 and BxPC-3 PC cells were adopted, after which the expression of miR-330-5p, PAX8 and LINC00958 were subsequently altered. RNA crosstalk was validated by dual-luciferase reporter gene assay. In order to detect whether LINC00958 could act as ceRNA to competitively sponge miR-330-5p and regulate PAX8, subcellular location of LINC00958 and interaction between LINC00958 and miR-330-5p were measured by FISH and RNA pull down respectively. The epithelial mesenchymal transition (EMT) process, cell invasion, and tumor growth were determined in vitro and in vivo. LINC00958 and PAX8 were up-regulated, while miR-330-5p was down-regulated during PC. LINC00958 mainly expressed in the cytoplasm and LINC00958 competitively sponged miR-330-5p. Upregulated miR-330-5p or downregulated PAX8 inhibited the EMT process as well as the invasion and metastasis ability of the PC cells. Moreover, the results indicated that miR-330-5p negatively targeted PAX8, and LINC00958 ultimately showcasing its ability to bind to miR-330-5p through its interaction with AGO2. Therefore, silencing of LINC00958 may bind to miR-330-5p to inhibit PAX8 in a competitive fashion, thereby preventing the progression of PC.

Robot-assisted duodenum-preserving pancreatic head resection with pancreaticogastrostomy for benign or premalignant pancreatic head lesions: a single-centre experience.

BACKGROUND: The purpose of this study was to compare short- and long-term outcomes of modified robot-assisted duodenum-preserving pancreatic head resection (RA-DPPHR) versus robot-assisted pancreaticoduodenectomy (RA-PD). METHODS: Matched for age, sex, ASA classification, tumour size, history of abdominal surgery and pathological type, 34 patients undergoing RA-DPPHR and 34 patients undergoing RA-PD between January 2010 and December 2016 were retrospectively analyzed. RESULTS: The RA-DPPHR group had shorter surgical time (188.2 vs. 386.3 min, p < 0.001) and less blood loss (168.2 vs. 386.3 ml, p = 0.026) but higher complication rate (47.1% vs. 32.4%, p = 0.105) and pancreatic fistula rate (32.4% vs. 17.6%, p = 0.161). Hospital mortality was 2.9%. Exocrine insufficiency was lower in the RA-DPPHR group (3.0% vs. 24.2%, p = 0.027). Endocrine insufficiency was observed in one RA-DPPHR patient and 5 RA-PD patients (p = 0.197). CONCLUSIONS: Modified RA-DPPHR benefits in terms of better conservation of exocrine and endocrine pancreatic functions at the expense of a significant morbidity and non-zero mortality.

MicroRNA-300 promotes apoptosis and inhibits proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/ß-catenin signaling pathway by targeting CUL4B in pancreatic cancer cells.

The study aims to verify the hypothesis that up-regulation of microRNA-300 (miR-300) targeting CUL4B promotes apoptosis and suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells by regulating the Wnt/ß-catenin signaling pathway. Pancreatic cancer tissues and adjacent tissues were collected from 110 pancreatic cancer patients. Expression of miR-300, CUL4B, Wnt, ß-catenin, E-cadherin, N-cadherin, Snail, GSK-3ß, and CyclinD1 were detected using qRT-PCR and Western blot. CFPAC-1, Capan-1, and PANC-1 were classified into blank, negative control (NC), miR-300 mimics, miR-300 inhibitors, siRNA-CUL4B, and miR-300 inhibitors + siRNA-CUL4B groups. The proliferation, migration, invasion abilities, the cell cycle distribution, and apoptosis rates were measured in CCK-8 and Transwell assays. Pancreatic cancer tissues showed increased CUL4B expression but decreased miR-300 expression. When miR-300 was lowly expressed, CUL4B was upregulated which in-turn activated the Wnt/ß-catenin pathway to protect the ß-catenin expression and thus induce EMT. When miR-300 was highly expressed, CUL4B was downregulated which in-turn inhibited the Wnt/ß-catenin pathway to prevent EMT. Weakened cell migration and invasion abilities and enhanced apoptosis were observed in the CUL4B group. The miR-300 inhibitors group exhibited an evident increase in growth rate accompanied the largest tumor volume. Smaller tumor volume and slower growth rate were observed in the miR-300 mimics and siRNA-CUL4B group. Our study concludes that lowly expressed miR-300 may contribute to highly expressed CUL4B activating the Wnt/ß-catenin signaling pathway and further stimulating EMT, thus promoting proliferation and migration but suppressing apoptosis of pancreatic cancer cells.

CUL4B promotes metastasis and proliferation in pancreatic cancer cells by inducing epithelial-mesenchymal transition via the Wnt/ß-catenin signaling pathway.

This study determines whether cullin 4B (CUL4B) promotes pancreatic cancer (PC) metastasis by inducing epithelial-mesenchymal transition (EMT) via the Wnt/ß-catenin signaling pathway. A total of 64 PC patients were enrolled in this study. Human PC cell lines were distributed into blank, negative control, shCUL4B, PLOC, PLOC-CUL4B, and PLOC-CUL4B + siRNA-ß-catenin groups. The expressions of CUL4B, Wnt/ß-catenin signaling pathway-related proteins, and EMT-related proteins were determined using RT-qPCR and Western blotting. The positive expressions of CUL4B and ß-catenin protein in tissues were detected by immunohistochemistry. MTT assay and flow cytometry was performed for cell proliferation and cell cycle, scratch test, and transwell assay for cell migration and invasion ability. CUL4B and ß-catenin were expressed at a higher level in PC tissues than in paracancerous tissues though paracancerous tissues had higher expressions of CUL4B and ß-catenin than normal tissues. The PLOC-CUL4B group showed increased CUL4B, Wnt, ß-catenin, LEF-1, c-Jun, Cyclin D1, N-cadherin, Vimentin, Snail, and ZEB1 expression; decreased E-cadherin expression; accelerated cell proliferation; increased S-phase cell percentages; increased cell migration ability; more liver metastases; and enlarged tumor than the PLOC and PLOC-CUL4B + siRNA-ß-catenin groups. The shCUL4B group showed decreased CUL4B, Wnt, ß-catenin, LEF-1, c-Jun, Cyclin D1, N-cadherin, Vimentin, Snail, and ZEB1 expression; increased E-cadherin expression; decelerated cell proliferation; decreased S-phase cell percentages; reduced cell migration ability; less liver metastases; and decreased tumor weight than the blank and negative control groups. We demonstrate that CUL4B promotes PC metastasis by inducing EMT via the Wnt/ß-catenin signaling pathway. Therefore, CUL4B might be the clinical target for treating PC.

Up-regulation of chemokine receptor CCR4 is associated with Human Hepatocellular Carcinoma malignant behavior.

Studies indicate that the chemokine receptor is responsible for poor prognosis of hepatocellular carcinoma (HCC) patients. In this study, we initially demonstrated that CCR4 is overexpressed in HCC specimens, and its elevation in HCC tissues positively correlates with tumor capsule breakthrough and vascular invasion. Although overexpression of CCR4 failed to influent proliferation of HCC cells in vitro apparently, the prominent acceleration on HCC tumor growth in vivo was remarkable. The underlying mechanism may be involved in neovascularization. Interestingly, different from effect on proliferation, CCR4 overexpression could trigger HCC metastasis both in vitro and in vivo also induced HCC cell epithelial-mesenchymal transition (EMT) as well. Then we identified matrix metalloproteinase 2 (MMP2) as a direct target of CCR4 which plays an important role in CCR4-mediated HCC cell invasion, which was up-regulated by ERK/AKT signaling. Positive correlation between CCR4 and MMP2 expression was also observed in HCC tissues. In conclusion, our study suggested that chemokine receptor CCR4 promotes HCC malignancy and facilitated HCC cell metastases via ERK/AKT/MMP2 pathway. These findings suggest that CCR4 may be a potential new diagnostic and prognostic marker in HCC, and targeting CCR4 may be a potential therapeutic option for blocking HCC metastasis.

The over expression of long non-coding RNA ANRIL promotes epithelial-mesenchymal transition by activating the ATM-E2F1 signaling pathway in pancreatic cancer: An in vivo and in vitro study.

This study aims to investigate the roles of lncRNA ANRIL in epithelial-mesenchymal transition (EMT) by regulating the ATM-E2F1 signaling pathway in pancreatic cancer (PC). PC rat models were established and ANRIL overexpression and interference plasmids were transfected. The expression of ANRIL, EMT markers (E-cadherin, N-cadherin and Vimentin) and ATM-E2F1 signaling pathway-related proteins (ATM, E2F1, INK4A, INK4B and ARF) were detected. Small molecule drugs were applied to activate and inhibit the ATM-E2F1 signaling pathway. Transwell assay and the scratch test were adopted to detect cell invasion and migration abilities. ANRIL expression in the PC cells was higher than in normal pancreatic duct epithelial cells. In the PC rat models and PC cells, ANRIL interference promoted the expressions of INK4B, INK4A, ARF and E-cadherin, while reduced N-cadherin and Vimentin expression. Over-expressed ANRIL decreased the expression of INK4B, INK4A, ARF and E-cadherin, but raised N-cadherin and Vimentin expressions. By inhibiting the ATM-E2F1 signaling pathway in PC cells, E-cadherin expression increased but N-cadherin and Vimentin expressions decreased. After ANRIL was silenced or the ATM-E2F1 signaling pathway inhibited, PC cell migration and invasion abilities were decreased. In conclusion, over-expression of lncRNA ANRIL can promote EMT of PC cells by activating the ATM-E2F1 signaling pathway.

Robot-assisted laparoscopic versus open middle pancreatectomy: short-term results of a randomized controlled trial.

OBJECTIVE: This first prospective randomized controlled trial was performed to compare short-term outcomes of robot-assisted laparoscopic middle pancreatectomy (RA-MP) with open middle pancreatectomy (OMP). BACKGROUND: RA-MP is a novel minimally invasive surgical technique for benign or borderline tumors in the pancreatic neck or body. Its short-term effectiveness and safety remain unknown, compared to OMP. METHODS: Patients eligible for MP from August 2011 to November 2015 were randomized into the RA-MP or OMP group. The primary endpoint was length of hospital stay (LOS). Secondary endpoints were intraoperative parameters, and postoperative and recovery variables. RESULTS: A total of 100 patients were included into the study to analyze primary and secondary endpoints. Demographic characteristics and pathological parameters were similar in both groups. Furthermore, LOS was significantly shorter (15.6 vs. 21.7 days, P = 0.002), median operative time was reduced (160 vs. 193 min, P = 0.002), median blood loss was lower (50 vs. 200 mL, P < 0.001), rate of clinical postoperative pancreatic fistula (POPF) was lower (18 vs. 36.0 %, P = 0.043), nutritional status recovery was better, off-bed return to activity was expedited (3.1 vs. 4.6 days, P < 0.001), and resumption of bowel movement was faster (3.5 vs. 5.0 days, P < 0.001) in the RA-MP group, compared to the OMP group. CONCLUSION: RA-MP was associated with significantly shorter LOS, reduced operative time, blood loss and clinical POPF rate, and expedited postoperative recovery, compared to OMP.

Robotic Enucleation for Benign or Borderline Tumours of the Pancreas: A Retrospective Analysis and Comparison from a High-Volume Centre in Asia.

BACKGROUND: Enucleation is increasingly performed for benign or borderline tumours of the pancreas because it is a parenchyma-sparing and less invasive procedure compared to conventional pancreatectomy, which reduces the risk of exocrine and endocrine insufficiency. This study retrospectively evaluated and compared the pre-, intra-, and post-operative clinical characteristics after open and robotic approaches for pancreatic enucleation. METHODS: Fifty-six cases of enucleation for benign or borderline tumours of the pancreas treated from March 2010 to July 2015 were identified by a retrospective search. These included 25 patients who underwent an open approach and 31 patients who underwent a robotic approach. The clinical characteristics were extracted and compared. RESULTS: The two groups had a similar location and pathology of the tumour. The robotic group had a significantly shorter operation time and significantly less blood loss than the open group. The rates of clinical pancreatic fistula (PF) formation and major complications were similar. The robotic approach could be applied for a tumour on the right side of the pancreas without increasing the incidence of clinical PF or other major complications. The patients with clinical PF had a significantly shorter distance between the lesion and the main pancreatic duct (MPD). CONCLUSION: Robotic enucleation appears to be a feasible and safe approach for benign or borderline tumours of the pancreas and was associated with similarly favourable surgical outcomes as the open approach. Identifying and avoiding the MPD is an important step during enucleation.

TMEM45B promotes proliferation, invasion and migration and inhibits apoptosis in pancreatic cancer cells.

In the present study, we focused on the expression and biological functions of TMEM45B in pancreatic cancer tissues and cell lines. Real-time PCR and Western blotting were used to examine the expression levels of TMEM45B in pancreatic cancer tissues and cell lines. The functions of TMEM45B were evaluated using CCK-8, flow cytometry and transwell analysis. Our results showed that TMEM45B exhibited high expression in pancreatic cancer tissues and cell lines compared with the normal pancreatic tissues and cells. Using gene set enrichment analysis (GSEA), we found that TMEM45B may regulate multiple genes involved in the cell cycle and metastasis pathways. Downregulation of TMEM45B by RNA interference significantly reduced proliferation, invasion and migration of SW1990 and PANC-1 cells, accompanied by the induction of cell cycle arrest and apoptosis, whereas overexpression of TMEM45B promoted proliferation, invasion and migration of CFPAC-1 cells as well as apoptosis inhibition. Taken together, our study provides evidence that TMEM45B is an oncogene involved in the tumorigenesis of pancreatic cancer and may represent a new molecular target for pancreatic cancer treatment.

Preparation of three-dimensional macroporous chitosan-gelatin B microspheres and HepG2-cell culture.

Chitosan-gelatin B microspheres with an open, interconnected, highly macroporous (100-200 µm) structure were prepared via a three-step protocol combining freeze-drying with an electrostatic and ionic cross-linking method. Saturated tripolyphosphate ethanol solution (85% ethanol) was chosen as the crosslinking agent to prevent destruction of the porous structure and to improve the biostability of the chitosan-gelatin B microspheres, with N-(3-dimethylaminopropyl)-N'-ethyl-carbodiimide/N-hydroxysuccinimide as a second crosslinking agent to react with gelatin A and fixed chitosan-gelatin B microspheres to attain improved biocompatibility. Water absorption of the three-dimensional macroporous chitosan-gelatin B microspheres (3D-P-CGMs) was 12.84, with a porosity of 85.45%. In vitro lysozyme degradation after 1, 3, 5, 7, 10, 14, and 21 days showed improved biodegradation in the 3D-P-CGMs. The morphology of human hepatoma cell lines (HepG2 cells) cultured on the 3D-P-CGMs was spherical, unlike that of cells cultured under traditional two-dimensional conditions. Scanning electron microscopy and paraffin sections were used to confirm the porous structure of the 3D-P-CGMs. HepG2 cells were able to migrate inside through the pore. Cell proliferation and levels of albumin and lactate dehydrogenase suggested that the 3D-P-CGMs could provide a larger specific surface area and an appropriate microenvironment for cell growth and survival. Hence, the 3D-P-CGMs are eminently suitable as macroporous scaffolds for cell cultures in tissue engineering and cell carrier studies. Copyright © 2014 John Wiley & Sons, Ltd.

Robotic approach improves spleen-preserving rate and shortens postoperative hospital stay of laparoscopic distal pancreatectomy: a matched cohort study.

BACKGROUND: Spleen preservation (SP) is beneficial for patients undergoing distal pancreatectomy of benign and borderline tumors; however, the conventional laparoscopy approach (C-LDP) is less effective in controlling splenic vessel bleeding. The benefits of the robotic-assisted approach (RA-LDP) in SP have not been clearly described. This study aimed to evaluate whether a robotic approach could improve SP rate and effectiveness/safety profile of laparoscopic distal pancreatectomy (LDP). METHODS: Matched for scheduled SP, age, sex, ASA classification, tumor size, tumor location, and pathological type, 69 patients undergoing RA-LDP and 50 undergoing C-LDP between January 2005 and May 2014 were included. Main outcome measures included SP rate, operative time (OT), blood loss, transfusion frequency, morbidity, postoperative hospital stay (PHS), and oncologic safety. RESULTS: Among matched patients scheduled for SP, RA-LDP was associated with significantly higher overall (95.7 vs. 39.4%) and Kimura SP rates (72.3 vs. 21.2%), shorter OT (median 120 vs. 200 min), less blood loss (median 100 vs. 300 mL), lower transfusion frequency (2.1 vs. 18.2%), and shorter mean PHS (10.2 vs. 14.5 days). Among matched patients scheduled for splenectomy, RA-LDP was associated with similar OT, blood loss, transfusion frequency, and PHS. The two approaches were similar in overall morbidity, frequency of pancreatic fistula, and oncologic outcome among patients undergoing splenectomy for malignant tumors. CONCLUSIONS: RA-LDP was associated with a significantly better SP rate and reduced OT, blood loss, transfusion requirement, and PHS for patients undergoing SP compared to C-LDP, but offered less benefits for patients undergoing splenectomy.

Robot-assisted laparoscopic versus open pancreaticoduodenectomy: a prospective, matched, mid-term follow-up study.

BACKGROUND: Robot-assisted laparoscopic pancreaticoduodenectomy is a novel minimally invasive surgery technique, and its effectiveness and safety remain unknown in patients with borderline malignant or malignant diseases. This study aimed to prospectively evaluate the effectiveness and safety of RLPD versus open PD (OPD). METHODS: Between January 2010 and December 2013, 180 eligible patients were prospectively hospitalized for elective RLPD (n = 60) or OPD (n = 120). They were matched for tumor location, tumor type, tumor size, ASA classification, age, and sex. The main outcome measures included demographics, intraoperative variables, morbidity, postoperative recovery, and mid-term evaluation. RESULTS: Over the study period, the RLPD group had a significantly longer but decreasing operative time (median 410 vs. 323 min; P < 0.001), less blood loss (median 400 vs. 500 mL; P = 0.005), better nutritional status recovery, expedited off-bed return to activity (3.2 vs. 4.8 d; P < 0.001), faster resumption of bowel movement (3.6 vs. 5.2 d; P < 0.001), and shorter hospital stay (20 vs. 25 d; P = 0.002) compared to the OPD group. The two groups had similar surgical morbidities and mortality as well as R0 resection rate and number of lymph nodes resected. Among patients with pancreatic adenocarcinoma, the two groups had similar overall and disease-free survival (ACTRN12614000299606). CONCLUSIONS: This first largest, prospective matched study demonstrated that for treating selected borderline and malignant pathologies, RLPD was associated with a significant learning curve effect and expedited postoperative recovery, but had a surgical and oncological safety profile similar to OPD.

Prognostic evaluation of patients undergoing living-donor liver transplant by APACHE II and MELD scores.

OBJECTIVES: We hypothesized that the combination of APACHE II and Model for End-Stage Liver Disease systems would work satisfactorily in patients admitted to intensive care unit after living-donor liver transplant. MATERIALS AND METHODS: Data were retrospectively collected from the database of our surgical team. The study included 38 patients (hepatitis B virus cirrhosis, 47.4%; hepatocellular carcinoma, 28.9%; other diseases, 23.7%). Laboratory values were obtained. Vital signs, Glasgow Coma scale scores, and urine output were abstracted. Variables included age, sex, acute physiology score, APACHE II score, APACHE II-predicted intensive care unit and hospital mortality, predicted length of intensive care unit, and hospital stay. Patients' actual length of intensive care unit and hospital stays, intensive care unit and hospital discharge status, and discharge location were recorded. Standardized mortality ratios were calculated. Discrimination and calibration of APACHE II were assessed. All patients were divided into 3 groups: Model for End-Stage Liver Disease score: >25, 18 to 25, and <18. Predicted hospital mortality was calculated and compared. RESULTS: Mean APACHE II scores of survivors and non-survivors were 13.03 and 23.67. Mean risk of death was 7.05% and 25.07%. APACHE II scores and risk of death between survivors and non-survivors was significantly different (P <.001). The cutoff value of APACHE II score and Model for End-Stage Liver Disease score in the receiving operating characteristic curve was 20 and 25. Patients with APACHE II scores greater than 20 or Model for End-Stage Liver Disease scores greater than 25 had higher predicted hospital mortality after living-donor liver transplant. CONCLUSIONS: The modified APACHE II model provides an accurate prognosis of patients receiving a living-donor liver transplant. The combined application of Model for End-Stage Liver Disease score and APACHE II score can improve the predictive accuracy.

Candidate microRNA biomarkers of pancreatic ductal adenocarcinoma: meta-analysis, experimental validation and clinical significance.

BACKGROUND: The diagnostic and prognostic value of microRNA (miRNA) expression aberrations in pancreatic ductal adenocarcinoma (PDAC) has been studied extensively in recent years. However, differences in measurement platforms and lab protocols as well as small sample sizes can render gene expression levels incomparable. METHODS: A comprehensive meta-review of published studies in PDAC that compared the miRNA expression profiles of PDAC tissues and paired neighbouring noncancerous pancreatic tissues was performed to determine candidate miRNA biomarkers for PDAC. Both a miRNA vote-counting strategy and a recently published Robust Rank Aggregation method were employed. In this review, a total of 538 tumour and 206 noncancerous control samples were included. RESULTS: We identified a statistically significant miRNA meta-signature of seven up- and three down-regulated miRNAs. The experimental validation results showed that the miRNA expression levels were in accordance with the meta-signature. The results from the vote-counting strategy were consistent with those from the Robust Rank Aggregation method. The experimental validation confirmed that the statistically unique profiles identified by the meta-review approach could discriminate PDAC tissues from paired nonmalignant pancreatic tissues. In a cohort of 70 patients, the high expression of miR-21 (p=0.018, HR=2.610; 95% CI=1.179-5.777) and miR-31 (p=0.039, HR=2.735; 95% CI=1.317-6.426), the low expression of miR-375 (p=0.022, HR=2.337; 95% CI=1.431-5.066) were associated with poor overall survival following resection, independent of clinical covariates. CONCLUSIONS: The identified miRNAs may be used to develop a panel of diagnostic and prognostic biomarkers for PDAC with sufficient sensitivity and specificity for use in a clinical setting.

Andrographolide causes apoptosis via inactivation of STAT3 and Akt and potentiates antitumor activity of gemcitabine in pancreatic cancer.

Gemcitabine is a first-line drug utilised in the chemotherapy of pancreatic cancer; however, this drug induces chemo-resistance and toxicity to normal tissue during treatment. Here, we firstly report that andrographolide (ANDRO) alone not only has anti-pancreatic cancer activity, but it also potentiates the anti-tumour activity of gemcitabine. Treatment with ANDRO alone inhibits proliferation of the pancreatic cancer cell lines in a dose- and time-dependent manner in vitro. Interestingly, ANDRO induces cell cycle arrest and apoptosis of pancreatic cancer cells by inhibiting STAT3 and Akt activation, upregulating the expression of p21(WAF1) and Bax, and downregulating the expression of cyclinD1, cyclinE, survivin, X-IAP and Bcl-2. Additionally, ANDRO combined with gemcitabine significantly induce stronger cell cycle arrest and more obvious apoptosis than each single treatment. The mechanistic study demonstrates that this synergistic effect is also dependent on the inhibition of STAT3 and Akt activations which subsequently regulates the pathways involved in the apoptosis and cell cycle arrest. Furthermore, both ANDRO alone and the combination treatments exhibit efficacious anti-tumour activity in vivo. Overall, our results provide solid evidence supporting that ANDRO alone or its combination with gemcitabine is a potential chemotherapeutic approach for treating human pancreatic cancer in clinical practice.

Clinical significance of RECK promoter methylation in pancreatic ductal adenocarcinoma.

The aim of this study was to analyze the clinical significance of reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) promoter methylation in pancreatic ductal adenocarcinoma (PDA). Methylation-specific polymerase chain reaction was used to examine the promoter methylation status of RECK in 60 pairs of PDA tissue samples and adjacent non-cancerous tissue samples. Statistical analyses were applied to test the associations between RECK promoter methylation status, clinicopathologic factors, and prognosis. The rate of RECK promoter methylation was significantly higher in PDA tissues than in adjacent non-cancerous tissues (P < 0.001). RECK methylation status was significantly associated with clinical stage (P = 0.017), histological differentiation (P = 0.046), and lymph node metastasis (P = 0.003), but was not associated with gender, age, and tumor location (all P > 0.05). Additionally, RECK promoter methylation is associated with malignant behavior and poor prognosis. In conclusion, determination of RECK promoter methylation status in tumor tissues may assist in the identification of patients who require aggressive postoperative intervention in order to improve prognosis.