Abstract:Benign tumors of the pancreas are not rare, and most of them require surgical treatment, of which enucleation or local resection is the ideal procedure. However, for lesions of relatively large size or very close to the main pancreatic duct, or when there is intraoperative injury of the main pancreatic duct, then segmental resection, pancreaticojejunostomy or pancreaticoduodenectomy are recommended by most clinical guidelines. The above-mentioned procedures for benign conditions of the pancreas will result in greater intentional surgical trauma, excessive pancreatic resection, and unavoidable anatomical and physiological changes. The authors performed an investigative clinical research in a new procedure for benign pancreatic diseases using an innovative theory of bridge closure. The procedure, chiefly based on main pancreatic duct bridging repair and end-to-end pancreatic anastomosis reconstruction, plastically repairs the defect of the pancreas after excision of the benign lesion and then restores the normal anatomy. Preliminary clinical results have verified the feasibility and safety of this theory and technique, which is hopeful to correct the traditional misunderstanding that the main pancreatic duct is unreconstructable, and completely change the surgical treatment modalities for benign pancreatic diseases.

Abstract:The prevalence of pancreatic cancer, which is characterized by low resection rates and dismal prognosis, is increasing with the years. Surgical resection remains the only possible radical treatment for this condition. Great progress has been achieved in surgical treatment of pancreatic cancer in recent years, as evidenced by the dramatically decreased perioperative mortality rates and incidence of postoperative complications, but the surgical resection rates and long-term results are still disappointing. The development of pancreatoduodenectomy has gone through three stages: the emergence of prototypical procedure, gradual maturity and perfection, and procedure standardization, to which, tremendous contributions have been made by a number of scholars. At present, a consensus on standardized lymphadenectomy for pancreatic cancer has been reached, and advocation of expanded lymphadenectomy for achieving a R0 resection on the basis of clinical research and the combined venous resection for improving resection rates have gained general acceptance by surgeons, but majority of them hold negative attitudes towards the combined arterial resection, with agreements on the feasibility of combined organ resection in a small number of cases with distant metastases after selection. Neoadjuvant therapy has become an intense area, but there is no consensus about the indications and detailed treatment suggestions so far. The molecular pathological classification for pancreatic cancer indicates the gain of deep understanding of this highly heterogeneous tumor, which will open a new avenue to break through the current challenges. Here, the authors overview the history and current state of surgical treatment for pancreatic cancer.

Abstract:Objective: To investigate the clinical value of organ preserving pancreatectomy in treatment of benign or low-grade malignant pancreatic tumors. Methods: The clinical data of 66 patients with pancreatic benign or low-grade malignant tumor who underwent organ preserving pancreatectomy from January 2009 to December 2016 in the Department of General Surgery of the First Affiliated Hospital, Nanchang University were retrospectively analyzed. Of the patients, the lesion included insulinoma in 34 cases, solid pseudopapillary tumor in 6 cases, serous cystadenoma in 9 cases, intraductal papillary mucinous tumor in 4 cases, and nonfunctional neuroendocrine tumor, paraganglioma and mucinous cystadenoma in one case each; 34 cases underwent tumor enucleation, 10 cases underwent middle segmental pancreatectomy, 13 cases underwent spleen-preserving distal pancreatectomy, 6 cases underwent pylorus-preserving pancreaticoduodenectomy and 3 cases underwent duodenum-preserving pancreatic head resection. Results: The mean operative time was (163.6±77.4) min, intraoperative blood loss was (234.4±242.7) mL, and length of postoperative hospital stay was (11.3±8.1) d. The incidence of overall abdominal complications, biochemical pancreatic leak, grade B/C pancreatic fistula, intra-abdominal infection, delayed gastric emptying and intra-abdominal bleeding were 36.4%, 15.2%, 10.6%, 6.1%, 3.0% and 1.5%, respectively. No reoperation was required and no death occurred in any of the patients. After the mean follow-up period of (47.2±25.6) months, the incidence of new-onset diabetes mellitus and requirement of pancreatic enzyme replacement therapy was 3.1% (the34 cases with insulinoma were excluded) and 1.5% respectively, and no recurrence or metastasis was observed. Conclusion: Organ preserving pancreatectomy can maximally preserve the pancreatic parenchyma and adjacent organs, avoid the excessive loss of pancreatic endocrine and exocrine functions and preserve the function of the spleen. It should be considered as the first option for treatment of benign or low-grade malignant pancreatic tumor.

Abstract:Objective: To investigate the clinical value of using enhanced recovery after surgery (ERAS) protocols in perioperative period of pancreaticoduodenectomy (PD). Methods: The clinical data of 42 patients undergoing radical PD in the Affiliated Tumor Hospital of Zhengzhou University from June 2015 to December 2016 were retrospectively analyzed. All patients received ERAS management during perioperative period. The clinical variables that included postoperative complications, length of hospitalization and readmission were recorded. Results: On postoperative day (POD) 1, all patients underwent routine removal of urinary catheter, of whom, 2 cases had catheter indwelling due to prostatic hyperplasia, 22 patients (52.4%) successfully ambulated and 10 patients (23.8%) achieved the scheduled activity standard. On POD 2, routine gastric tube removal was performed, but the gastric tube was reintroduced in 5 cases for occurrence of delayed gastric emptying and 30 cases (71.4%) tolerated the liquid diet. On POD 3, abdominal drainage tube was removed in 35 cases (83.3%). On POD 4, 33 patients (78.6%) tolerated solid diet intake. The postoperative complications included pancreatic leakage in 3 cases, bile leakage in 1 case, bleeding in 1 case, abdominal fluid collections in 3 cases, delayed gastric emptying in 4 cases, and lung infection in 1 case, with an overall incidence of postoperative complications of 31.0%, which were all resolved after symptomatic treatment. No death occurred. The median length of hospitalization was 10 (8–35) d. Three patients (7.1%) patients required hospital readmission within 30 d of discharge, and of whom, one was for gastric insufficiency, one for abdominal fluid collection with infection and one for biliary tract infection. Conclusion: Application of ERAS in perioperative period of PD is safe and feasible, which can reduce the length of hospitalization without increase of incidence of postoperative complications and readmission rate.

Abstract:Objective: To investigate the influential factors and prediction for early postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD), so as to guide the earlier removal of abdominal drainage tube to accelerate postoperative recovery of the patients. Methods: The clinical data of 430 patients undergoing PD in Southwest Hospital from January 2013 to October 2015 were reviewed. The risk factors and their predictive values for early POPF were analyzed by univariate and multivariate statistical analysis, and receiver operating characteristic (ROC) curve, respectively. Results: Early POPF occurred in 116 patients (26.9%) of the total 430 patients. In addition, among the patients without early POPF, the incidences of POPF, intra-abdominal infections and overall complications were all significantly reduced in those with abdominal drainage tube removed within postoperative day (POD) 5 compared with others with abdominal drainage tube retained more than POD 5 (3.1% vs. 12.1%; 9.2% vs. 20.3%; 24.5% vs. 42.0%, all P<0.05). The results of univariate and multivariate Logistic regression analysis showed that drain fluid amylase on POD 1 (DFA1) and serum amylase on POD 1(SA1) were independent risk factors for early POPF following PD (OR=1.000 and 1.004, 95% CI=1.000–1.001 and 1.001–1.006, both P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of DFA1 for predicting early POPF was 0.916 which was obviously larger than that of SA1 (0.745), and the sensitivity, specificity, and the positive and negative predictive value were 91.7%, 80.8%, 62.7%, and 96.5% for DFA1≥494.75 IU/L, respectively. Conclusion: DFA1 is an important risk and predictive factor for early POPF after PD. In patients with DFA1<494.75 IU/L, the abdominal drainage tube can be safely removed and then fast track recovery protocol can be adapted on POD 3.

Abstract:Objective: To investigate clinical manifestations, risk factors, diagnosis and treatment of pancreatico-enteric anastomotic stenosis after pancreaticoduodenectomy (PD). Methods: The clinical data of patients developing pancreatico-enteric anastomotic stenosis after PD treated from January 2008 to January 2018 were reviewed. The diagnosis and treatment process and follow-up results of the patients were analyzed and summarized. Results: Six patients developing pancreatico-enteric anastomotic stenosis after PD were enrolled, of whom, the primary disease in one case was serous cystadenoma, two cases was duodenal papillary carcinoma, two patients was chronic pancreatitis and one case was ampullary carcinoma; 5 cases underwent pancreaticojejunostomy and one case underwent pancreaticogastrostomy; perioperative complications occurred in 3 cases, including biochemical leak, grade B pancreatic fistula and delayed gastric emptying in one case each. The main manifestation of the 6 patients was repeated onset of acute pancreatitis with no obvious predisposing cause after PD, and their pancreatico-enteric anastomotic stenosis were diagnosed by MRCP and/or CT. The median time from PD to diagnosis was 54 (15–84) months. After diagnosis, 5 patients underwent reconstruction of the pancreatico-enteric anastomosis, of whom, no special discomforts were noted in 2 cases within 6- and 8-month follow-up period respectively, and acute pancreatitis recurrence occurred and with repeated onset in the remaining 3 cases during follow-up from 6 to 39 months; one patient refused further surgery and subsequently still suffered from repeated onset of acute pancreatitis. Conclusion: Pancreatico-enteric anastomotic stenosis is one of the rare complications after PD. The stenosis frequently occurs in the pancreatic duct opening. Its potential risk factors include chronic pancreatitis, postoperative pancreatic fistula, intra-abdominal infection and pancreaticogastrostomy. Its main manifestation is repeated onset of acute pancreatitis. Reconstruction of the pancreatico-enteric anastomosis is a commonly used and safe treatment method, but the recurrence rate of pancreatitis after surgery is still high.

Abstract:Objective: To investigate the diagnosis and treatment methods as well as prognosis of pancreatic neuroendocrine tumors (pNETs). Methods: The clinical data of 8 patients with pNETs treated from January 2008 to January 2017 in the Affiliated Hospital of Inner Mongolia Medical University were retrospectively analyzed. Results: Of the 8 patients, two cases were male and 6 cases were female, and the age ranged from 36 to 72 years with an average age of 53 years; the lesions in all cases were ascertained by imaging examinations; 5 cases were non-functioning tumors with main symptoms of abdominal pain or bloating, abdominal mass, inappetence and emaciation, and 3 caseswere functioning tumors with main symptoms of hypoglycemic reaction or hyperglycemia; one case underwent tumor enucleation, two cases underwent distal pancreatectomy, 4 cases underwent pancreaticoduodenectomy and one case underwent distal pancreatectomy plus splenectomy with pancreaticojejunostomy. The 8 patients were followed up for 30 to 66 months, during which period, 7 cases were still alive, and one case died. Conclusion: Combination of laboratory tests and imaging examinations will be helpful for the diagnosis of this condition, and rational and feasible combined treatment can increase the cure rate, and improve the quality of life and prognosis of the patients.

Abstract:Objective: To analyze the clinical features as well as the diagnosis and treatment methods of pancreatic neuroendocrine neoplasms (PNENs). Methods: The clinical data of 5 patients with PNENs treated from June 2013 to June 2016 were retrospectively analyzed. Results: Of the 5 patients, 2 cases were male and 3 were female and age ranged from 48 to 57 years. All of the cases underwent ultrasound and CT examination, and one case had PET-CT examination. The clinical manifestations were varied with no specificity and the results of laboratory tests showed no significant findings. Four cases underwent surgical treatment, and one case underwent puncture biopsy only. The pathological results (based on the 2010 WHO classification) showed stage G1 in 2 cases, stage G2 in 1 case, and stage G3 in 2 cases, respectively. All of the 5 patients were followed up; one case died at 12 months postoperatively due to liver metastasis and the remaining cases recovered well. Conclusion: Most PNENs lack characteristic clinical manifestations, so preoperative diagnosis is difficult and it mainly depends on postoperative pathology. Surgery-based multimodality therapy is the main treatment method for PNENs, and offers better prognosis.

Abstract:Objective: To investigate the effect of down-regulating G protein signal regulating protein 2 (GPSM2) expression on chemotherapy sensitivity of pancreatic cancer cells. Methods: The pancreatic cancer MIA-PaCa-2 cells with low GPSM2 expression were constructed and identified. Sixteen nude mice were equally randomized into two groups, and were subcutaneously implanted with MIA-PaCa-2 cells with low GPSM2 expression and MIA-PaCa-2 cells with natural GPSM2 expression to establish the tumor-bearing models. After that, half mice underwent gemcitabine injection (100 mg/kg) and half mice were given saline of the same volume in each group (intraperitoneal injection, 3 times per week for 4 weeks). The tumor growth curves were drawn, and all mice were sacrificed on the third day after the last injection, and the volumes of the tumor xenografts were determined. Results: The pancreatic cancer MIA-PaCa-2 cells with low GPSM2 expression were successfully created. Both growth speed and volume of the tumor xenografts presented a decreasing trend as natural GPSM2 expression plus saline group>natural GPSM2 expression plus gemcitabine group>low GPSM2 expression plus saline group>low GPSM2 expression plus gemcitabine group. The result of factorial design showed that the main effect of either gemcitabine alone or down-regulating GPSM2 gene expression alone on tumor growth inhibition had statistical significance (both P=0.000), while the interaction effect of gemcitabine combined with down-regulating GPSM2 gene expression on tumor growth inhibition did not reach a statistical significance (P=0.073), but the simple effect of gemcitabine combined with down-regulating GPSM2 gene expression on tumor growth inhibition had statistical significance compared with gemcitabine alone or down-regulating GPSM2 gene expression alone (P=0.000 and 0.003). Conclusion: Whether down-regulating GPSM2 gene expression will enhance chemotherapy sensitivity of pancreatic cancer cells cannot be confirmed. However, the inhibitory effect of down-regulating GPSM2 gene expression with simultaneous chemotherapy on pancreatic cancer is remarkably greater than that of their single actions.

Abstract:

Objective: To investigate the expression of long non-coding RNA BCAR4 (LncRNA BCAR4) in pancreatic carcinoma cells and its effects on proliferation and apoptosis of pancreatic carcinoma cells. Methods: The expressions of LncRNA BCAR4 in different pancreatic carcinoma cell lines (AsPC-1, HPAC, BxPC-3 and Panc-1) and normal pancreatic duct epithelial cells HPDE6-C7 were determined by qRT-PCR method. The pancreatic carcinoma AsPC-1 cells were transfected with BCAR4 siRNA or crambled sequences, with untransfected AsPC-1 cells as blank control, and then the cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry, and the protein expression levels of p-mTOR and p-P70S6K as well as phosphorylated mTOR (p-mTOR) and phosphorylated P70S6K (p-P70S6K) were detected by Western blot analysis. Results: The relative expression levels of LncRNA BCAR4 in all studied pancreatic carcinoma cell lines were significantly higher than that in normal pancreatic duct epithelial HPDE6-C7 cells (all P<0.05). After BCAR4 siRNA transfection, AsPC-1 cells exhibited decreased proliferation, increased apoptosis rate and down-regulated p-mTOR and p-P70S6K expressions (all P<0.05). Conclusion: LncRNA BCAR4 expression is increased in pancreatic carcinoma cells. High LncRNA BCAR4 expression can promote proliferation and inhibit apoptosis of the pancreatic carcinoma cells, and the mechanism may be associated with its up-regulating phosphorylation level of mTOR/P70S6K pathway.

Abstract:Objective: To assess the clinical efficacy of necrotic pancreatic tissue removal through a small incision along the existing tract of the PCD tube combined with percutaneous nephroscope in treatment of severe acute pancreatitis (SAP) complicated with infected necrosis. Methods: In 23 SAP patients at infection stage after receiving poor treatment such as inadequate drainage, a small incision approximately 2 cm in length along the tract of the PCD tube was made, through which, the necrotic pancreatic tissue in the superficial areas was removed with a lithotomy forceps, and in the deep areas was cleared visually by baskets via the combined percutaneous nephroscope. A douche tube and a double cannula were respectively inserted in the superior area and the inferior area of the residual space after necrotic pancreatic tissue removal, and the tubes were then brought out through abdominal wall at relatively thin sites and secured in places. The previous incision wound of PCD tube was closed. After above operation, the residual necrotic tissue was gradually cleared by irrigation of the purulent cavity with normal saline through the douche tube, and continuous drainage of the double cannula under a negative pressure. The drainage volume (difference between input and output), body temperature, white blood cell (WBC) counts, procalcitonin (PCT) and C-reactive protein (CRP) before and after treatment were monitored and recorded. Review abdominal CT examination was performed on one month after surgery to check the residual necrotic tissue around the pancreas. Results: In the 23 SAP patients at infection stage and underwent the above treatment, the symptoms of infection or intoxication were all improved, the drainage volumes were significantly increased within postoperative day 30 compared with preoperative level (all P<0.05), and the infection indexes (body temperature, WBC count, PCT and CRP) were significantly decreased at different time points after operation compared with their preoperative levels (all P<0.05). About one month after the operation, the result of review CT examination showed peripancreatic necrosis tissue and collections had largely disappeared. Douche tube change was required in 5 patients due to drainage tube blockage at 2 weeks postoperatively. No complications such as abdominal hemorrhage, intestinal leakage or perforation occurred, and no minimally invasive surgical intervention or open surgery was required in any of them. Finally, all patients recovered and were discharged. Conclusion: Necrotic pancreatic tissue removal through a small incision along the tract of PCD tube combined with percutaneous nephroscope has demonstrable clinical efficacy in treatment of SAP complicated with infected necrosis.

Abstract:Objective: To investigate the surgical treatment strategies for infected pancreatic necrosis (IPN) and the situations of carbapenem-resistant enterobacteriaceae (CRE) infection. Methods: The clinical data of 118 IPN patients treated the Department of Biliopancreatic Surgery of Xiangya Hospital, Central South University from January 2010 to September 2017 were reviewed, and the cases with CRE infection was critically analyzed. Results: In the entire group of 118 IPN patients (3 cases did not undergo surgical treatment), the number of total surgical interventions was 328 times, with an average of 2.77 times per case, and the mortality rate was 20.3% (24/118), in which, the mortality rate in patients with bloodstream infection was significantly higher than in those without bloodstream infection [(39.5% (17/43) vs. 9.0% (7/75), P<0.001]. In the 31 cases (26.3%) with CRE infection, the number of total surgical interventions was 100 times, with an average of 3.22 times per case, of whom, 27 cases underwent a step-up approach treatment, and 4 cases underwent a step-down approach treatment, with a mortality rate of 32.3% (10/31). In IPN patients with CRE infection compared with IPN patients without CRE infection, the severity of acute pancreatitis was upgraded, mortality rate was increased, and length of ICU stay was prolonged significantly (all P<0.05). In addition, the mortality rate of IPN patients was gradually reduced over the past 8 years, but the proportion of CRE infection was markedly elevated during the past 4 years. Conclusion: IPN mainly depends on surgical treatment at present. CRE have become the main pathogenic bacteria of IPN, and are also associated with more severe conditions and longer the ICU stay. Step-up approach is becoming the mainstream surgical strategy for IPN associated with CRE.

Abstract:Objective: To investigate the selection of timing for laparoscopic cholecystectomy in patients with acute biliary pancreatitis (ABP). Methods: Ninety-six ABP patients admitted during March 2014 to January 2017 were enrolled. Of the patients, 47 cases underwent conservative treatment before laparoscopic cholecystectomy and common bile duct exploration (observation group), and 49 cases were subjected to laparoscopic cholecystectomy and common bile duct exploration directly (control group). The main clinical variables between the two groups of patients were compared. Results: In observation group compared with control group, the number of cases requiring postoperative analgesics (19 cases vs. 9 cases), average operative time (1.9 h vs.1.6 h), average time to postoperative recovery of peristalsis (2.6 d vs.1.9 d), number of cases with postoperative wound infection (7 cases vs.1 case), number of cases requiring open conversion (6 cases vs.1 case), average volume of postoperative drainage (56.9 mL vs. 32.4 mL), and average length of postoperative hospital stay (6.2 d vs. 4.5 d) were reduced and overall treatment effective rate (81.6% vs. 95.7%) was increased significantly (all P<0.05). Follow-up was conducted for 9 to 39 months, and repeated ABP was noted. Conclusion: For ABP, administering conservative treatment first until pancreatitis subsides prior to laparoscopic cholecystectomy is safe and feasible, and it is recommended to be used in clinical practice.

Abstract:Pancreatic cancer is a common malignant tumor currently, and its mortality is nearly equal to its morbidity. How to improve early diagnosis and treatment efficiency of pancreatic cancer has become an urgent issue. The role of tumor markers in screening patients with pancreatic cancer, assessing treatment efficacy and detecting postoperative recurrence has become increasingly important. In this paper, the authors mainly discuss the role of tumor markers for diagnosis and prognosis estimation of pancreatic cancer through reviewing the research progress of tumor makers in the body fluids such as the blood serum and pancreatic juice of pancreatic cancer patients and current problems.

Abstract:Acute pancreatitis (AP) is an acute abdomen often seen in clinical practice, and its treatment remains a clinical challenge, because the pathogenesis has not been clarified yet. Studies have demonstrated that autophagy plays a very important role in the pathogenesis of AP, which can lead to the activation of trypsinogen in pancreatic acinar cells and cause the occurrence and aggravation of the inflammatory reactions. Here, the authors address the research progress of the basic molecular mechanisms of autophagy and its action mechanism in AP.

Abstract:Acute pancreatitis (AP) is a common digestive disease in clinical practice. A large number of studies have showed that many types of alkaloids exert therapeutic effect on AP, especially on severe acute pancreatitis (SAP). Alkaloids are widely distributed in the plant kingdom, and most of them exist in dicotyledonous plants. Here, the authors address the progress concerning the therapeutic effect of several types of currently known alkaloids on AP and their action mechanisms.