Abstract:Objective: To investigate the clinical pathological features, and diagnosis and treatment as well as prognosis of pancreatic acinar cell carcinoma. Methods: The clinical data of 14 patients with pancreatic acinar cell carcinoma treated in the Department of General Surgery of China-Japan Friendship Hospital from January 1997 to January 2017 were retrospectively analyzed. Results: Of the 14 patients, 10 cases were males and 4 cases were females, with an average age of (51.6±15.6) years; the initial symptoms included abdominal pain in 7 cases, jaundice in 3 cases, nausea and vomiting in 1 case, and abdominal mass in 1 case, while 2 cases were asymptomatic and discovered by health examination. The average tumor diameter was (9.4±5.2) cm. The tumor was located in the body and tail of the pancreas in 10 cases (64%), in the head of the pancreas in 3 cases and the uncinate process in 1 case. All preoperative puncture biopsies and intraoperative frozen sections failed to identify pancreatic acinar cell carcinoma. R0 resection was achieved in 9 patients, and 5 patients received only pancreas biopsy or palliative resection due to liver metastasis or adjacent organ invasion. All patients were diagnosed as pancreatic acinar cell carcinoma by postoperative pathological findings. The results of immunohistochemical staining showed that positive expression rates of α-antitrypsin, α-antichymotrypsin and cytokeratin (AE I/AE3) were 100%. The mean survival time of the 9 patients with R0 resection was (32.0±25.6) months, while that of 5 patients without R0 resection was only (4.0±0.8) months. Conclusion: For pancreatic acinar cell carcinoma with a likelihood of R0 resection, aggressive surgical resection should be performed, even in the presence of liver metastases. Postoperative adjuvant chemotherapy is associated with better prognosis.

Abstract:Objective: To evaluate the clinical efficacy of using external drainage of the pancreatic duct with a stent after pancreaticoduodenectomy (PD). Methods: The studies comparing the external drainage of pancreatic duct with a stent and non-drainage after PD from January 2000 to December 2017 were collected by searching the relevant databases such as PubMed, EMBASE, the Cochrane Library and Web of Science. After assessment and data extraction of the selected studies, Meta-analysis was performed. Results: Four randomized controlled trials (RCTs) were finally included, involving 458 patients with 227 cases in external drainage group and 231 cases in non-drainage group. The results of Meta-analysis showed that the overall incidence of pancreatic fistula was significantly reduced in external drainage group compared with non-drainage group (RR=0.57, 95% CI=0.40–0.82, P=0.002), which was mainly contributed by reducing the grade B and C pancreatic fistula (RR=0.57, 95% CI=0.38–0.85, P=0.006) and exerting effect in patients with pancreatic duct diameter ≤ 3.0mm (RR=0.55, 95% CI=0.37–0.82, P=0.003). In addition, the incidence of pancreatic fistula was also significantly reduced in external drainage group compared with non-drainage group among patients undergoing duct-to-mucosa anastomosis (RR=0.42, 95% CI=0.22–0.80, P=0.008). Moreover, the overall incidence of postoperative complications was significantly decreased in external drainage group compared with non-drainage group (RR=0.79, 95% CI=0.64–0.98, P=0.03). There were no significant differences in incidence of delayed gastric emptying, abdominal bleeding, intra-abdominal fluid collections, and wound infection as well as the overall postoperative mortality (all P>0.05). Conclusion: Using external drainage of the pancreatic duct with a stent after PD can effectively reduce the incidence of pancreatic fistula and postoperative complications. However, this conclusion still needs to be further verified by large sample and high quality RCTs.

Abstract:Objective: To compare the clinical efficacy of modified pancreaticojejunostomy versus conventional pancreaticojejunostomy in pancreaticoduodenectomy. Methods: Using a retrospective historical approach, the clinical data of 79 patients with periampullary tumors undergoing conventional pancreaticojejunostomy for digestive tract reconstruction (conventional pancreaticojejunostomy group) from Jan 2014 to Nov 2015, and 87 patients with periampullary tumors undergoing modified pancreaticojejunostomy for digestive tract reconstruction (modified pancreaticojejunostomy group) from Dec 2015 to Dec 2017, were analyzed. The conventional pancreaticojejunostomy was end-to-side anastomosis between the remnant pancreas and lateral jejunal wall, and the modified pancreaticojejunostomy was mucosa-to-mucosa anastomosis between the remnant pancreas and lateral jejunal wall. The main clinical variables between the two groups were compared. Results: There were no significant differences in general data, surgical procedures, overall operative time, and intraoperative blood loss between the two groups (all P>0.05). Despite the similar overall operative times between the two groups, the time for pancreaticojejunostomy in modified pancreaticojejunostomy group was two times of that in conventional pancreaticojejunostomy group. The incidence of grade A or B pancreatic fistula in the modified pancreaticojejunostomy group was significantly lower than that in conventional pancreaticojejunostomy group (P=0.027 and 0.019), and the incidence of biliary fistula or abdominal infection was also significantly lower than that in conventional pancreaticojejunostomy group (P=0.014 and 0.011). The incidence of grade C pancreatic fistula, intestinal fistula, intra-abdominal bleeding, and delayed gastric emptying showed no statistical differences between the two groups (all P>0.05). Conclusion: Compared with the conventional pancreaticojejunostomy, the modified pancreaticojejunostomy offers reduced incidence of grade A and B pancreatic fistula, biliary fistula and abdominal infection. Although this modified procedure has somewhat prolonged operative time, it is recommended to be further used in clinical practice.

Abstract:Objective: To evaluate the efficacy of using enhanced recovery after surgery (ERAS) protocols in perioperative management of pancreaticoduodenectomy (PD). Methods: The studies comparing the use of ERAS protocols and conventional protocols in perioperative management of PD were collected by searching several national and international literature databases. After literature screening according to the inclusion and exclusion criteria, Meta-analysis was performed by using the Review Manager 5.3 software. Results: Four randomized controlled trials and 11 clinical controlled trials were finally included, involving 2 185 patients, with 1 036 cases in ERAS group and 1 149 cases in non-ERAS group. The results of Meta-analysis showed that the length of postoperative hospital stay was significantly reduced (MD=–4.38, 95% CI=–4.73– –4.04, P<0.000 01), the time to the first postoperative flatus (defecation) was significantly shortened (MD=–1.34, 95% CI= –2.33––0.35, P=0.008), and the overall incidence of postoperative complications was significantly decreased (RR=0.66, 95% CI=0.57–0.75, P<0.000 01) in ERAS group compared with non-ERAS group; there were no significant differences in terms of the incidence of postoperative delayed gastric emptying, pancreatic fistula and biliary fistula, as well as in-hospital mortality and readmission rates (all P>0.05). Conclusion: Current evidence indicates that ERAS can promote bowel function recovery, decrease length of hospital stay and incidence of postoperative complications in patients undergoing PD. So it is recommended to be used in clinical practice.

Abstract:Objective: To investigate the expression of endoplasmic reticulum oxidoreductin-1-like protein (ERO1L) in pancreatic cancer tissue and its clinical significance. Methods: The ERO1L mRNA expressions in 82 specimens of pancreatic cancer tissue and 12 specimens of normal pancreatic tissue adjacent to pancreatic cancer were determined by qRT-PCR method. The relations of ERO1L mRNA expression level with the clinicopathologic characteristics as well as the disease-free survival and overall survival rate of the pancreatic cancer patients were analyzed. Results: The relative expression level of ERO1L mRNA in pancreatic cancer tissue was significantly higher than that in adjacent normal pancreatic tissue (2.63 vs. 1.12, P<0.01). The expression of ERO1L mRNA was significantly associated with the degree of tumor differentiation, distant metastasis, clinical stage and lymph node metastasis of the patients (all P<0.05), but irrelevant to gender, age, tumor size and tumor location of the patients (all P>0.05). Survival analysis showed that the 1- and 3-year disease-free survival rate and overall survival rate in patients with high ERO1L mRNA expression was significantly lower than those in patients with low ERO1L mRNA expression (all P<0.01). The univariate and multivariate analyses revealed that ERO1L mRNA expression level was an independent risk factor for postoperative disease-free survival and overall survival in pancreatic cancer patients (both P<0.05). Conclusion: ERO1L expression is increased in pancreatic cancer tissue. The high expression of ERO1L is closely associated with the malignant clinicopathologic features of the pancreatic cancer patients and is also an independent prognostic factor for pancreatic cancer patients.

Abstract:Objective: To investigate the expression of human phosphatidylethanolamine-binding protein 4 (hPEBP-4) in pancreatic cancer tissue and its clinical significance. Methods: The mRNA and protein expressions of hPEBP-4 in specimens of pancreatic cancer and paired adjacent tissues from 30 patients were determined by qRT-PCR, Western blot and immunohistochemical staining, respectively. The relations of the hPEBP-4 expression with clinicopathologic variables and prognosis of the pancreatic cancer patients were analyzed. Results: The results of qPCR and Western blot showed that the mRNA and protein expressions of hPEBP-4 were obviously up-regulated in 24 specimens of the 30 pancreatic cancer tissues relative to their adjacent tissues. The results of immunohistochemical staining showed that the high expression rate of hPEBP-4 in pancreatic cancer tissues was significantly higher than that in adjacent tissues (80.0% vs. 16.7%, χ2=24.093, P<0.001). The expression level of hPEBP-4 was significantly related to the degree of tumor differentiation, serum CA19-9 level and TNM stage (all P<0.05). The results of correlation analysis showed that the differentiation degree of pancreatic cancer and TNM staging were negatively correlated with hPEBP-4 (r=–0.507, P=0.004; r=–0.400, P=0.028), while serum CA19-9 level was positively correlated with hPEBP-4 (r=0.428, P=0.018). The results of survival analysis showed that the overall survival rate in patients with low hPEBP-4 expression was significantly higher than that in patients with high hPEBP-4 expression (χ2=8.658, P=0.003). Conclusion: The expression of hPEBP-4 is increased in pancreatic cancer tissue, which is associated with some malignant pathological features and poor prognosis in pancreatic cancer.

Abstract:Objective: To screen the prognostic risk long noncoding RNAs (lncRNAs) for pancreatic ductal adenocarcinoma (PDAC) by bioinformatics approaches. Methods: The RNA-Seq Level 2 data and clinical information of PDAC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The sequencing data of the downloaded mRNAs and lncRNAs were re-annotated according to the gene annotation data from NCBI Gene database and GENCODE v7 database. The differentially expressed mRNAs and lncRNAs were screened by using edgeR and limma packages in R. Then, the significantly co-expressed pairs between mRNAs and lncRNAs were obtained by correlation analysis, in which, the mRNAs were considered as target genes of the lncRNAs. After that, the functional modules of the lncRNAs were predicted by functional enrichment analysis of their target mRNAs with the clusterProfiler package in R. Finally, the significant prognostic risk lncRNAs for PDAC were determined by drawing Kaplan-Meier curves of the differentially expressed lncRNAs. Results: After gene re-annotation, the sequencing data of a total of 19 791 mRNAs and 1 623 lncRNAs were obtained, and then, 260 differentially expressed mRNAs and 15 differentially expressed lncRNAs were picked up. From the correlation analysis, 24 significantly co-expressed pairs comprised of 24 mRNAs and 5 lncRNAs were identified. Of them, LINC00857 had 6 target genes that were C1orf116, ESRP1, GPRC5A, LIPH, MAL2 and PLS1, respectively. According to the functional enrichment analysis, the target genes of lncRNA LINC00857 were mainly enriched in phospholipase activity, structural constituent of cytoskeleton, and lipase activity. The results of survival analysis revealed that lncRNA CASC8 and LINC00857 were significantly associated with prognostic risk of PDAC (P=0.0052, P=0.027). Conclusion: CASC8 and LINC00857 are potential prognostic risk lncRNAs for PDAC, and may probably become the novel indictors for prognosis of PDAC in the future.

Abstract:Objective: To investigate the copy number variation (CNV) of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene in pancreatic cancer and its relationship to the prognosis of pancreatic cancer patients.
Methods: The CNV and RNA Seq V2 data in the Cancer Genome Atlas (TCGA) were used for analysis of correlation between the CDKN2A gene CNV and its mRNA expression, and the influence of CDKN2A gene CNV on the expressions of other genes. The difference in CDKN2A gene expressions between normal subjects and pancreatic cancer patients was compared and the relation of CDKN2A gene CNV with the prognosis of pancreatic cancer patients was analyzed by using TCGA database and GTEx database. Functional enrichment analysis of CDKN2A and its co-expressed genes was performed by using gene ontology analysis (GO analysis) in DIVAD combined with KEGG.
Results: By mining the TCGA database, CDKN2A gene CNV was found to be positively correlated with its mRNA expression (Pearson: r=0.102, Spearman: r=0.257). The expression levels of HOXC6 and SLC2A1 mRNA were significantly increased, while the expression levels of GGA2 and MTAP mRNA were significantly decreased in pancreatic cancer with CDKN2A gene (all P<0.05), and the correlation analysis showed that CDKN2A gene was positively correlated with MTAP mRNA (Pearson: r=0.42, Spearman: r=0.55). The CDKN2A gene expression in pancreatic cancer tissues was found to be significantly higher than that in normal pancreatic tissues by analyzing the GTEx database (P<0.05). The overall survival rate and tumor-free survival rate of pancreatic cancer patients with CDKN2A gene CNV were significantly reduced compared with those without CDKN2A gene CNV (both P<0.05). Functional enrichment analysis of co-expressed genes related to CDKN2A showed that the functions of these co-expressed genes were mainly concentrated in the signal pathways of cell cycle.
Conclusion: CDKN2A gene CNV is an unfavorable prognostic factor for pancreatic cancer and can be used as an indicator for estimating the prognosis of pancreatic cancer.

Abstract:Objective: To investigate the miR-519d expression in pancreatic cancer cells, and its actions. Methods: The miR-519d expressions in pancreatic cancer cell lines AsPC-1, BxPC-3, Capan-2 and Panc-1 as well as in normal pancreatic duct epithelial cell line HPDE6-C7 were detected by qRT-PCR. The Panc-1 cells were transfected with miR-519d over-expression plasmid (miR-519d group) and negative plasmid (negative control group) respectively, with untreated Panc-1 cells as blank control group. After that, the proliferative and invasion abilities, apoptosis and expression of X-linked inhibitor of apoptosis protein (XIAP) were determined by MTT assay, Transwell assay, flow cytometry and Western blot analysis, respectively. Results: The relative expression level of miR-519d in each pancreatic cancer cell line was significantly lower than that in normal pancreatic duct epithelial HPDE6-C7 cells (all P<0.05). In cells of miR-519d group compared with blank control group, the proliferative ability was reduced (significantly reduced after 72-h culture), the apoptosis rate was significantly increased, the invasion ability was significantly decreased and the expression level of XIAP protein was significantly down-regulated (all P<0.05). All the differences of the observed parameters in negative control group and blank control group showed no statistical significance (all P>0.05). Conclusion: The miR-519d expression is down-regulated in pancreatic cancer cells. Down-regulation of miR-519d expression can enhance the proliferative and invasion abilities, and decrease apoptosis in pancreatic cancer cell lines, and these actions may be associated with its regulating XIAP protein expression.

Abstract:Objective: To investigate the risk factors for early peripancreatic infection secondary to acute pancreatitis (AP). Methods: The clinical data of 826 consecutive AP patients admitted within 72 h after onset between January 2010 and October 2016 in Xiangya Hospital, Central South University were analyzed retrospectively. Of the patients, the clinical characteristics and results of blood tests within 24 h after admission were compared between cases who developed peripancreatic infection and those without peripancreatic infection during hospitalization to analyze the risk factors for peripancreatic infection, and further, the risk factors for peripancreatic infection in patients with severe acute pancreatitis (SAP) were analyzed separately. Results: Of the 826 AP patients, 30 cases (3.6%) developed peripancreatic infection. The results of univariate and multivariate Logistic analyses showed that the persistent organ failure for more than 48 h (OR=21.143, P<0.001), male sex (OR=11.659, P=0.003) and decrease of albumin (OR=0.872, P=0.006) within 24 h after admission were independent risk factors for developing peripancreatic infection. Of the 59 patients with SAP, 21 cases (35.6%) developed peripancreatic infection during their hospital stay. The results of univariate and multivariate Logistic analyses revealed that persistent organ failure for more than one week (OR=7.47, P=0.007) was the independent risk factor for developing the peripancreatic infection. Conclusion: Persistent organ failure in the early stage, male sex and the decrease of albumin within 24 h after admission are risk factors for developing peripancreatic infection in AP patients, and the risk of peripancreatic infection is increased with the prolongation of the duration of organ failure.

Abstract:Objective: To analyze the morbidity situation of fungal infected pancreatic necrosis (IPN) as well as its surgical treatment and clinical outcomes. Methods: The clinical data of 145 consecutive patients with IPN treated in Xiangya Hospital of Central South University from January 2010 to July 2018 were retrospectively analyzed, with a particular focus on those associated with fungal IPN. Results: Of the 145 IPN patients, a total of 46 cases were fungal IPN (31.7%); the results of time distribution analysis showed that fungal IPN had the highest proportion in the last two years (2017 to 2018), which reached 40.7%; all the 46 patients were monilial infections, which were caused mainly by monilia albicans (25 cases), secondly by candida albicans (14 cases) and thirdly by candida tropicalis (7 cases). Of the 46 patients, 41 cases underwent step-up treatment approach and 5 cases received step-down treatment approach. In fungal IPN patients, the number of total surgical interventions was 159 times, and the average number of surgical interventions was significantly higher than that in non-fungal IPN patients (3.5 times per case vs. 2.7 times per case, P<0.05). The mortality rate in the entire group of patients was 22.1% (32/145), which in fungal IPN patients was 17.3% (8/46) and in non-fungal IPN patients was 24.2% (24/99), and the difference had no significance (P>0.05). Of the 46 patients, 4 cases had concomitant bloodstream fungal infection, in whom, the mortality rate was significantly higher than that in those without bloodstream fungal infection [75% (3/4) vs. 14.3% (5/42), P<0.05]. Conclusion: The incidence of fungal IPN exhibits a rising trend. Although fungal infection does not increase the mortality in IPN patients, it always requires more surgical interventions, and the mortality is significantly increased when combined with bloodstream fungal infection. Thus, proper selection of antifungal agents and thorough control of the source of infection are the essential prerequisites for successful treatment of fungal IPN.

Abstract:Objective: To investigate the feasibility and effectiveness of nursing intervention based on multidisciplinary collaboration and integration in patients undergoing per-oral cholangiopancreatoscopy (PCPS) during the period of diagnosis and treatment. Methods: Ninety-six patients with pancreatobiliary duct diseases requiring PCPS treatment were randomly allocated by the order of admission to observation group (49 cases) and control group (47 cases). During the period of diagnosis and treatment, the patients in control group received conventional nursing intervention, while those in observation group received nursing intervention based on multidisciplinary collaboration and integration, which mainly included the informed consent, discussion before diagnosis and treatment, risk assessment, psychological preparation of patient, PCPS specific preparation, cooperation between medical and nursing care, nurse-patient cooperation and the intra- and postoperative supervision. Using the State-Trait Anxiety Inventory (STAI), Frankl Scale and self-designed questionnaires, the degree of anxiety, medical compliance, comfort level and satisfaction rate of the patients of the two groups were assessed, and the systolic blood pressure, heart rate and complications of the patients were also recorded. Results: Observation group was significantly superior to control group in terms of degree of anxiety, changes in systolic blood pressure and heart rate, patients’ medical compliance and comfort levels (all P<0.05). Meanwhile, the satisfaction rate was significantly increased after intervention and the incidence of treatment-associated complications was significantly reduced (all P<0.05). Conclusion: Through nursing intervention based on multidisciplinary collaboration and integration during the period of diagnosis and treatment, the stress discomforts such as anxiety and depression can be alleviated, the changes in blood pressure and heart rate can be reduced, the medical compliance, comfort level and satisfaction rate can be improved, and the incidence of complications can be decreased in patients undergoing PCPS.

Abstract:Objective: To investigate the optimization of preoperative preparation processes in the operating room and its application value in gastrointestinal surgery. Methods: One hundred and twenty five patients undergoing gastrointestinal surgery were selected. Before the start of surgery, 35 cases received the collaborative optimization measures that were established after discussion among anesthesiologists, surgeons and operating room nurses (optimization group), while 90 cases received the conventional approaches (conventional group). The playback data from the video surveillance cameras of the operating room of the two groups of patients were analyzed. Results: Regardless of whether dividing the operative positions or not, the preparation times from the initiation of induction of anesthesia to the start of surgery in optimization group were all significantly shorter than those in conventional group (all P<0.05). In supine position surgery, the times from initiation of induction of anesthesia to start of urinary catheterization, from the end of urinary catheterization to start of operation site disinfection, and from completion of draping to start of surgery in patients receiving optimization measures were all significantly superior to those receiving conventional approaches (all P<0.05); in lithotomy position surgery, the times from initiation of induction of anesthesia to patient positioning, from end of patient positioning to start of operation site disinfection, and from completion of draping to start of surgery in patients receiving optimization measures were all significantly superior to those receiving conventional approaches (all P<0.05). Conclusion: The established optimization measures based on multidisciplinary team collaboration can help to reduce the changeover times between processes and time for inducing anesthesia, and thereby boost the efficiency of the operating room.

Abstract:Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor that is prone to micrometastasis, lacks obvious symptoms in early stage, but often invades the surrounding healthy tissues. The majority of patients are found to be at an advanced stage at the time of diagnosis, the 5-year survival rates of those with localized cancer and metastatic cancer are only 23% and 5%, respectively. Therefore, how to improve the survival rate of PDAC patients, optimize the therapeutic schedule and increase the cure rate are currently urgent issues. At present, operation-based multidisciplinary treatment and individualized treatment mode have become the research focuses, which include the pathogenetic mechanism, staged treatment strategy, neoadjuvant therapy and postoperative monitoring of PDAC. The authors address the research progress of various treatment methods for PDAC.

Abstract:At present, the clinical treatment of pancreatitis is mainly supportive, with long period of hospitalization, high medical expenses and high mortality. Therefore, it is urgent to find a new treatment strategy. Mesenchymal stem cells (MSCs) are considered to be ideal seed cells for tissue or organ repair in regenerative medicine, due to well-established self-renewal, multi-lineage differentiation potential, low immunogenicity, as well as immunomodulatory properties. In the last few years, several studies have found that MSCs can not only home to the damage area, but also promote the repair of pancreas injury through anti-inflammation, anti-apoptosis, angiogenesis and immune regulation. These studies suggest that MSCs therapy is a promising strategy for the treatment of pancreatitis. Here, the authors address the latest progress in MSCs therapy for acute and chronic pancreatitis.

Abstract:Infected pancreatic necrosis (IPN) is a serious complication of acute pancreatitis and it is also a leading cause of death. Minimally invasive debridement of the necrotic pancreatic tissue combined with antibiotics is currently the main treatment method for IPN. IPN is mostly involving hospital-acquired infections, with complex spectrum, frequent multidrug-resistant bacteria, and difficult choice of antibiotics. At present, the clinical data on the pathogens and drug resistance of IPN patients are limited, so understanding the risk factors for its occurrence, bacterial spectrum, drug resistance and related prognosis can provide better diagnosis and treatment for these patients.