Volume 29,Issue 9,2020 Table of Contents

1 Analysis of values of FRS and a-FRS for predicting pancreatic fistula after different types of pancreatic surgery

SHEN Jian , SUN Yan , GUO Feng , REN Dianyun , QIN Gengdu , JIN Xin , WU Heshui

2020, 29(9):1029-1036. DOI: 10.7659/j.issn.1005-6947.2020.09.001

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Abstract:
Background and Aims: Pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) are common surgical approaches for pancreatic tumors. Postoperative pancreatic fistula (POPF) is one of the most serious complications following pancreatic surgery, if the occurrence of POPF can be reliably predicted that will be of great clinical significance. The fistula risk score (FRS) and alternative fistula risk score (a-FRS) are two widely used prediction models for POPF, and however, the predictive efficiencies of FRS and a-FRS for POPF need further validation. This study was conducted to compare the predictive value of the FRS and a-FRS for POPF following DP and PD, so as to provide the theoretical basis and reference for the selection of the appropriate prediction model in clinical practice.
Methods: The clinical data of all patients undergoing pancreatic surgery between 2018 and 2019 in a single center were retrospectively collected, and the enrolled patients after screening for exclusion criteria were used as study subjects. The incidence rates of POPF in the whole group of patients and patients undergoing different surgery types (PD and DP) were counted, and the predictive efficiencies of the two scoring models in predicting POPF for the whole group and different surgery types were compared using area under the ROC curve (AUC).
Results: A total of 339 patients were included after exclusion of the ineligible cases, with 193 patients undergoing PD and 146 cases undergoing DP. The incidence of POPF was 17.4% in the entire group, and was 18.1% and 16.4% in PD group and DP group, respectively. FRS and a-FRS had a similar predictive ability for POPF in the whole group (AUC: 0.67 vs. 0.65, P=0.412), and the predictive value of FRS for POPF was better than that of a-FRS in PD group (AUC: 0.74 vs. 0.67, P=0.006), but FRS showed no predictive value for POPF in DP group (AUC=0.57, 95% CI=0.44–0.70, P=0.285), while the predictive ability of a-FRS for POPF was better than that of FRS in DP group (AUC: 0.66 vs. 0.57, P=0.048). Moreover, the incidence rates of POPF were increased in either the whole group, PD group or DP group with the increase of the risk grade classified by either FRS or a-FRS. Among the predictive factors of FRS, there were significant differences in intraoperative blood loss and diameter of the main pancreatic duct between DP group and PD group (both P<0.05).
Conclusion: Both FRS and a-FRS can be used for predicting POPF. However, FRS has a better predictive value than that of a-FRS for POPF following PD, but is unsuitable for POPF following DP, while a-FRS may be helpful for predicting POPF flowing DP. Blood loss and diameter of the main pancreatic duct may be responsible for the poor predictive ability of FRS for POPF following DP. However, these conclusions still need to be further verified due to the limitations of the study.

2 Predictive value of pancreatic stellate cell activity for postoperative pancreatic fistula after pancreaticoduodenectomy

CAO Xintong , ZHU Shuai , LUO Gengqiu , LIN Jiayan , NING Caihong , LI Jiarong , SHEN Dingcheng , WANG Xitao , HUANG Gengwen ,

2020, 29(9):1037-1044. DOI: 10.7659/j.issn.1005-6947.2020.09.002

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Abstract:
Background and Aims: The texture of the pancreas is an important factor for the occurrence of postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy (PD). However, there are no objective evaluation criteria for estimating the hardness of the pancreatic texture. Studies have demonstrated that the activation of the pancreatic stellate cells (PSCs) is closely associated with the pancreatic fibrosis, and therefore, their activity may probably influence the texture of the pancreas. This study was designated to investigated the feasibility and effectiveness of using the degree of PSC activity for predicting the clinically relevant postoperative pancreatic fistula (CR-POPF) after PD.
Methods: The surgical margin samples from 101 consecutive patients who underwent PD in the Department of Pancreatic Surgery, Xiangya Hospital, Central South University from December 2017 to September 2019 were prospectively collected. The degree of PSC activity was determined and graded by immunohistochemical staining of α-smooth muscle actin (α-SMA) protein. The relations of PSC activity with CR-POPF and the pancreatic texture, as well as the relations of other relevant clinicopathologic factors with CR-POPF were analyzed. The efficiency of PSC activity in predicting CR-POPF was determined by ROC analysis.
Results: In the 101 patients, CR-POPF occurred in 41 cases (40.6%). Results of analysis showed that the incidence of CR-POPF was decreased progressively with the increase of the grade of PSC activity, and the distributions of PSC activity grades were significantly different among different pancreatic textures (both P<0.001). Results of correlation analysis showed that the degree of PSC activity was positively correlated with the hardness of pancreatic texture (r=0.456, P<0.001), while was negatively correlated with the incidence of CR-POPF (r=–0.539, P<0.001). Results of univariate analysis showed that pancreatic texture, tumor pathology, PSC activity grade, preoperative body mass index, pancreatic duct diameter, preoperative total bilirubin, drainage fluid amylase on postoperative day 1 were significantly associated with the occurrence of CR-POPF (all P<0.05), and the results of multivariate Logistic regression analysis showed that the PSC activity (OR=0.24, 95% CI=0.10–0.56, P<0.001) and preoperative total bilirubin (OR=1.01, 95% CI=1.00–1.01, P=0.008) were the independent risk factors for CR-POPF. Results of ROC analysis showed that the AUC of the degree of PSC activity for predicting CR-POPF was 0.795 (95% CI=0.708–0.881), with a sensitivity of 63.3% and a specificity of 87.8%.
Conclusion: The degree of PSC activity can objectively and accurately reflect the hardness of the pancreatic texture. It is an effective index for predicting the CR-POPF following PD, and has certain clinical application value.

3 Clinical value of imbedding pancreaticojejunostomy in reducing pancreatic fistula after laparoscopic pancreaticoduodenectomy: a report of 69 cases

SHI Chengjian , ZHU Feng , WANG Min , TIAN Rui , ZHANG Hang , QIN Renyi

2020, 29(9):1045-1050. DOI: 10.7659/j.issn.1005-6947.2020.09.003

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Abstract:
Background and Aims: Pancreatic fistula is a common complication after pancreatectomy, which can lead to abdominal hemorrhage or infections and even death of the patients. Laparoscopic pancreatoduodenectomy (LPD) is a widely used pancreatic surgery. Compared with traditional open surgery LPD has the advantages of shorter hospital stay, lower blood loss and higher overall long-term survival rate, but it still has a high incidence of postoperative pancreatic fistula. Pancreaticojejunostomy for digestive tract reconstruction is closely related to the serious complications such as postoperative hemorrhage and pancreatic fistula, which is also a key point being focused on and continuously improved. Among many pancreaticojejunostomy methods, anastomosis of the pancreatic duct and jejunal mucosa is a widely accepted anastomotic method in the world at present time. However, pancreatic duct-to-jejunal mucosa anastomosis has a significant degree of technical difficulty during LPD, and the risk of pancreatic fistula is still high. Imbedding pancreaticojejunostomy is a new anastomotic method developed by the author's team after years of exploration and practice. The purpose of this study was to evaluate the clinical value of this method in reducing the incidence of pancreatic fistula after LPD.
Methods: The clinical data of 69 patients who received imbedding pancreaticojejunostomy during LPD from January 2018 to December 2018 were reviewed. The general data (age, sex), perioperative variables (total operative time, operative time for pancreaticojejunostomy, intraoperative blood loss, postoperative complications such as pancreatic fistula, bile leakage, bleeding, abdominal infection, and pathological results) were collected and analyzed.
Results: LPD was successfully performed in all the 69 patients, and 4 patients received a combined portal vein/superior mesenteric vein resection and (or) repair. The total operative time was (264.5±27.2) min, the operative time for pancreaticojejunostomy was (25.7±7.2) min, and the intraoperative blood loss was (85.5±19.5) mL. Postoperative pancreatic fistula occurred in 2 patients, including grade B and grade C pancreatic fistula in each case; postoperative bile leakage occurred in 1 patient (1.4%), which healed after non-surgical treatment, such as strengthening the nutrition and inhibiting the secretion of digestive fluid; postoperative abdominal hemorrhage occurred in 2 patients (2.8%), of whom, the bleeding was control in one case by intravenous infusion of hemostatic drugs and blood transfusion, and in the other case by intravenous infusion of hemostatic drugs, blood transfusion and interventional therapy; abdominal infection occurred in 1 patient (1.5%), which was related to pancreatic fistula, and was cured by adjusting abdominal drainage tube and abdominal puncture drainage tube. The average length of postoperative hospital stay was (15.7±1.3) d. The postoperative pathology showed that there were 23 cases of pancreatic head cancer, 6 cases of pancreatic serous cystadenoma, 3 cases of solid pseudopapilloma, 1 case of intraductal papillary mucinous tumor, 21 cases of duodenal papillary carcinoma, 7 cases of ampullary carcinoma and 8 cases of distal common bile duct carcinoma.
Conclusion: Imbedding pancreaticojejunostomy can effectively reduce the incidence rates of pancreatic fistula and other related complications after LPD, which is more suitable for laparoscopic operation, and is a reliable method of pancreaticojejunostomy. So, it is recommended to be widely used in clinical practice.

4 Application of modified continuous penetrating-suture pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy

QIAN Daohai , WANG Guannan , SHEN Zhengchao , FANG Xiaosan , HAN Meng , WANG Xiaoming

2020, 29(9):1051-1059. DOI: 10.7659/j.issn.1005-6947.2020.09.004

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Abstract:
Background and Aims: Laparoscopic pancreaticoduodenectomy (LPD) is one of the most complex operations in general surgery, characterized by long operative time, difficult resection, numerous anastomoses and high incidence of complications. Particularly, the postoperative pancreatic fistula (POPF) following LPD, which may cause the abdominal infection, bleeding and even death seriously restrict further development and application of this technique. Therefore, the avoidance of POPF has become an urgent problem to be solved. The authors previously have applied the continuous penetrating-suture pancreaticojejunostomy in LPD, which yielded satisfying results, but still has some limitations. So, this study was conducted to further observe the clinical efficacy of using the modified continuous penetrating-suture pancreaticojejunostomy in LPD.
Methods: Twenty-five patients admitted to Yijishan Hospital from June 2017 to December 2019 for LPD were randomly divided into two groups, and underwent continuous penetrating-suture pancreaticojejunostomy (control group, 15 cases) or modified continuous penetrating-suture pancreaticojejunostomy (observation group, 10 cases) during LPD, respectively. The latter was namely that 2 U-shaped sutures were performed on the cut surface of the pancreas to reinforce the cut surface of the pancreas prior to performing the continuous penetrating-suture pancreaticojejunostomy. The main clinical variables between the two groups of patients were compared.
Results: There was no significant difference in each preoperative variable between the two groups of patients (all P>0.05). LPD was successfully completed in all the 25 patients. There were no significant differences in the average operative time and intraoperative blood loss between the two groups (both P>0.05), but the average operative time for pancreaticojejunostomy in observation group was significantly longer than that in control group (23.50 min vs. 20.20 min, P=0.003). There was no significant difference in the overall incidence of pancreatic fistula between the two groups (P>0.05), but the incidence of grade B pancreatic fistula in observation group was significantly lower than that in control group (0 vs. 40%, P=0.028); the overall incidence of other postoperative complications such as abdominal infection and bleeding was lower in observation group than that in control group, but the difference did not reach a statistical significance (0 vs. 33.3%, P=0.057); the time for removal of the drainage tube placed near the pancreaticojejunostomy (11.00 d vs. 25.60 d, P<0.001) and length of hospital stay (12.20 d vs. 18.53 d, P=0.045) in observation group were significantly shorter than those in control group.
Conclusion: Modified penetrating-suture pancreaticojejunostomy is a simple and convenient method, and its application in LPD is safe and reliable, which not only reduces the incidence of grade B pancreatic fistula, but speeds up the postoperative recovery of the patients. So, it is recommended to be widely used in clinical practice.

5 Influence of cryptotanshinone on biological behaviors of pancreatic cancer cells and the action mechanism

HUANG Zhiwei , TAN Peng , DU Yichao , SHI Hao , CHEN Hao , QIAN Baolin , LIU Yu , FU Wenguang , LI Qiu

2020, 29(9):1060-1068. DOI: 10.7659/j.issn.1005-6947.2020.09.005

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Abstract:
Background and Aims: Pancreatic cancer is a highly malignant tumor of the digestive system. Although the current treatment for pancreatic cancer is constantly evolving, the prognosis of pancreatic cancer patients is still poor. Cryptotanshinone (CPT) is a monomer extracted from Chinese medicinal herb salvia miltiorrhiza with variety of activities, which has been proven to have anti-cancer potential against cervical cancer and prostate cancer, etc. However, its effect on pancreatic cancer is still unclear. This study was conducted to investigate the effect of CPT on the growth and migration of pancreatic cancer cells in vitro and the possible mechanism, so as to provide theoretical and experimental basis for the development of relevant drugs for clinical use.
Methods: The human pancreatic cancer BxPC-3 and SW1990 cells were used as study subjects. In these two types of pancreatic cancer cells, the concentration and time effects of CPT on cell viability were determined after treatment with different concentrations (10, 20 and 40 μmol/L) of CPT for different times (0, 1, 2 and 3 d); the changes in abilities of colony formation, migration and invasion after treatment with above concentrations of CPT for 24 h were determined by colony forming assay, scratch wound healing assay and Transwell assay, respectively; the expressions of Akt, phosphorylated Akt (p-AKT), and the epithelial-mesenchymal transition (EMT)-associated proteins vimentin and E-cadherin as well as the cell cycle-related proteins CDK4, cyclin D1 after treatment with 20 μmol/L CPT for different times were determined by Western blot analysis. The cells for control were treated with the vehicle (DMSO) only.
Results: In the two types of pancreatic cancer cells compared with corresponding control group, the growth abilities were significantly inhibited after CPT treatment, with a concentration- and time-dependent manner (all P<0.05); the degree of wound healing, relative colony formation rate and number of invading cells were significantly reduced, with a concentration-dependent manner (all P<0.05); the protein expressions of Akt, p-Akt, vimentin and E-cadherin, CDK4 and cyclin D1 were all significantly down-regulated, with a time-dependent manner (all P<0.05).
Conclusion: CPT can effectively inhibit the growth and migration of pancreatic cancer cells, and the mechanism may be probably associated with its downregulating the expression of Akt and thereby, cause the cell cycle arrest and inhibition of the EMT process of the pancreatic cancer cells.

6 Expression of lncRNA TUG1 pediatric in hepatoblastoma and its association with miR-204-mediated JAK2-STAT3 pathway

YUAN Miaoxian , YIN Qiang , JI Chunyi , XIE Weixin

2020, 29(9):1069-1075. DOI: 10.7659/j.issn.1005-6947.2020.09.006

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Background and Aims: Although a certain progress has been made in the treatment of hepatoblastoma (HB) in children, the overall clinical prognosis is still poor. So, exploring its pathogenesis and effective therapeutic targets are of great importance. This study was conducted to investigate the expressions of the long non-coding RNA taurine-upregulated gene 1 (TUG1) and the molecules associated with JAK2-STAT3 pathway in HB tissue and preliminarily analyze the relationship between TUG1 and miR-204-mediated JAK2-STAT3 angiogenic signaling pathway.
Methods: Sixty pediatric patients with HB admitted in Hunan Children’s Hospital from March 2017 to April 2018 were enrolled as study subjects. The HB tumor tissues along with the tumor-adjacent normal tissues of the patients were collected. The protein expressions of JAK2, STAT3 and their downstream angiogenesis-related molecules in the tissue samples were detected by immunohistochemical staining and Western blot, respectively. The RNA expressions of TUG1 and miR-204 as well as JAK2 and STAT3 and their downstream angiogenesis-related molecules in the tissue samples were determined by qRT-PCR method, and the correlation between TUG1 and miR-204 expressions in HB tissue was analyzed. Moreover, in human HB cell line HepG2, the changes in RNA and protein expression levels of JAK2, STAT3 and their downstream angiogenesis-related molecules were analyzed after TUG1 knockdown or miR-204 overexpression.
Results: The results of immunohistochemical staining showed that the positive expression rates of both JAK2 and STAT3 HB tissue were significantly higher than those in tumor-adjacent normal tissue (JAK2: 40.1% vs. 16.9%; STAT3: 55.7% vs. 19.8%, both P<0.05). The results of qRT-PCR showed that the RNA expression levels of TUG1, miR-204 as well as JAK2 and STAT3 and their downstream angiogenesis-related molecules that included VEGF, VEGFR2 and HIF-1α were significantly up-regulated in HB tissue than those in tumor-adjacent normal tissue (all P<0.05), and there was a significant negative correlation between TUG1 and miR-204 expressions in HB tissue (r=–0.962, P=0.014). The results of Western blot showed that the protein expression levels of JAK2 and STAT3 and their downstream angiogenesis-related molecules were significantly upregulated in HB tissue than those in tumor-adjacent normal tissue (all P<0.05). In HepG2 cells after TUG1 knockdown or miR-204 overexpression, the RNA and protein expressions of JAK2 and STAT3 and their downstream angiogenesis-related molecules were significantly down-regulated (all P<0.05).
Conclusion: In the tumor tissues from HB children, the expressions of TUG1 is up-regulated, accompanied with the increased activity of JAK2-STAT3 pathway, and there is also a negative correlation between TUG1 and miR-204 expressions. These findings suggest that TUG1 can probably activating the JAK2-STAT3 pathway and thereby promote the angiogenesis through inhibiting miR-204 expression in HB.

7 Prognostic value of the systemic immune-inflammation index in patients with pancreatic cancer: a systematic review and Meta-analysis

ZHOU Faquan , CHEN Shi , SUN Hongyu , TANG Lijun

2020, 29(9):1076-1083. DOI: 10.7659/j.issn.1005-6947.2020.09.007

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Background and Aims: The relationship between systemic immune index (SII) and prognosis in patients with pancreatic cancer is controversial at present, and there are also no large sample multi-center studies to provide confirmation. This study was conducted to systematically explore the prognostic significance of SII in pancreatic cancer by Meta-analysis, so as to provide evidence for improving patients’ prognosis and individualized treatment.
Methods: A computer-based searching was conducted in several national and international databases, and the publicly published studies on the relationship between SII and the prognosis of pancreatic cancer were collected. The retrieval time was from inception to March 2020. After literature screening, data extraction and bias risk evaluation by two independent reviewers, Meta-analysis was conducted using Stata 12.0 software.
Results: Five cohort studies were included involving a total of 3 086 patients. Results of Meta-analysis showed that the overall survival (OS) was shortened (HR=1.26, 95% CI=1.13–1.40, P<0.001) and the cancer-specific survival (CSS) was poor (HR=2.232, 95% CI=1.55–3.48, P<0.001) in pancreatic cancer patients with high SII, while SII had no significant relation with the disease-free survival (DFS) of pancreatic cancer patients (HR=1.27, 95% CI=0.95–1.70, P<0.106). Subgroup analysis found that high SII was associated with shortened OS (HR=1.39, 95% CI=1.14–1.69, P=0.001) when the threshold value of SII was greater than or equal to 600, and was irrelevant to OS (HR=1.22, 95% CI=0.97–1.54, P=0.089) when the threshold value of SII was less than 600. High SII was associated with shorter OS as evidenced by studies from Austria and the United States (HR=1.40, 95% CI=1.07–1.84, P=0.016; HR=1.37, 95% CI=1.02–1.84, P=0.004), but was unrelated to OS as demonstrated by studies from China (HR=1.22, 95% CI=0.97–1.54, P=0.089). High SII was related to the shortened OS in patients undergoing surgical treatment and non-surgical treatment (HR=1.40, 95% CI=1.07–1.84, P=0.004; HR=1.38, 95% CI=1.18–1.61, P<0.001), but was not associated with OS in those undergoing mixed treatment (HR=1.09, 95% CI=0.92–1.29, P=0.303). High SII was connected to shortened OS in patients with either AJCC stage I-III or III-IV disease (HR=1.39, 95% CI=1.14–1.69, P<0.001; HR=1.38, 95% CI=1.14–1.66, P<0.001), and high SII was relevant to shortened OS in patients either before or after treatment (HR=1.39, 95% CI=1.19–1.62, P<0.001; HR=1.37, 95% CI=1.02–1.84, P=0.037). In addition, SII, the neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio had a predictive effect on OS in pancreatic cancer patients, while CA19-9 did not. None of the above 4 factors had predictive effect on DFS, but all had predictive effect on CSS.
Conclusion: High SII may be an independent risk factor for poor prognosis in pancreatic cancer patients. Limited by the quantity and quality of the studies, the above conclusion needs to be verified by more high-quality studies.

8 Analysis of risk factors for early postoperative recurrence of pancreatic ductal adenocarcinoma and application value of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy

ZHU Lei , LI Shanshan , GU Hongzhu , WANG Yang

2020, 29(9):1084-1090. DOI: 10.7659/j.issn.1005-6947.2020.09.008

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Abstract:
Background and Aims: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant digestive tumor, and the patients may face a risk of early postoperative recurrence (recurrence within postoperative 6 months) even after radical resection. Further, the perioperative risk factors for predicting early recurrence remain unclear so far. This study was designated to investigate the risk factors for early postoperative recurrence of PDAC, and the clinical value of preoperative neoadjuvant chemotherapy (NAC) and postoperative adjuvant chemotherapy (PAC) in preventing early recurrence of PDAC.
Methods: The clinical data of 141 patients with PDAC who underwent pancreatectomy in Panjin Liao-Oil Gem Flower Hospital from January 2011 to December 2016 were retrospectively analyzed. Of the patients, 64 cases (47.5%) received NAC and 103 cases (73.0%) received PAC; recurrence occurred in 45 cases and did not occur in 96 cases within postoperative 6 months.
Results: The results of univariate analysis showed that TNM stage, preoperative CA19-9 level, NAC, postoperative complications, postoperative CA19-9 level and PAC were associated with early postoperative recurrence (all P<0.05). The results of comparative analysis among different treatment methods, the incidence of early local recurrence in patients undergoing NAC (undergoing NAC or NAC+PAC) was lower than those without NAC (undergoing pure surgery or PAC) (partial P<0.05); the incidence of early distant metastasis in patients undergoing PAC (undergoing PAC or PAC+NAC) was lower than those without PAC (undergoing pure surgery or NAC) (all P<0.05). The results of multivariate analysis showed that the advanced TNM stage (III vs. I: HR=1.866, 95% CI=1.148–3.035, P=0.012; III vs. II: HR=1.790, 95% CI=1.044–3.068, P=0.035), postoperative CA19-9 level above 37 IU/mL (HR=1.998, 95% CI=1.200–3.325, P=0.008) and absence of PAC (HR=1.962, 95% CI=1.176–3.273, P=0.010) were independent risk factors for early postoperative recurrence.
Conclusion: TNM stage, postoperative CA19-9 level and PAC are important predictor of early recurrence of PDAC. Although PAC is an important preventive measure against the early recurrence, particularly distant metastasis of PDAC, NAC can effectively prevent the early local recurrence of PDAC. So, there is a potential complementary association between the two regimens.

9 Clinical efficacy of laparoscopic treatment for functional insulinoma: a report of 11 cases

CUI Yongyi , MA Hongyan , ZHANG Guojie , ZHANG Chunchen

2020, 29(9):1091-1097. DOI: 10.7659/j.issn.1005-6947.2020.09.009

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Background and Aims: Insulinoma is the most common functional islet-cell tumor of the pancreas, and surgery is the only cure for this condition. With the development of technology and equipment, laparoscopic surgery has been accepted by doctors and patients. This study was conducted to evaluate the feasibility and efficacy of laparoscopic insulinoma enucleation.
Methods: The perioperative clinical data and follow-up results of 11 patients who underwent laparoscopic insulinoma resection in the authors’ institute from July 2016 to May 2019 were retrospectively analyzed.
Results: Among the 11 patients, there were 4 males and 7 females. The patients were aged 21-62 years with an average age of 44.8 years at the time of hospital attendance. The course of disease ranged from 8 d to 4 years, and all patients were diagnosed with insulinoma according to preoperative qualitative and localization examinations. Laparoscopic tumor resection was successfully performed in 10 patients, including tumor enucleation in 8 patients (2 with tumor located in the neck of the pancreas, 5 cases in the body, and 2 cases in the tail), and resection of the body and tail of the pancreas in 2 patients (1 case in the body, and 2 cases in the tail). Intraoperative laparoscopic ultrasound examination was performed in all the 11 patients, by which, a total of 11 tumors were detected in 10 cases, and no lesion was found in 1 case, so the operation was aborted. The operative time was 85.0–380.0 min, and intraoperative blood loss was 10.0–530.0 mL. At 30 min after tumor resection, the blood glucose increased by 1.5–2.3 mmol/L; blood glucose was 3.9–10.4 mmol/L on the first postoperative day in the morning, and 2.4–12.8 mmol/L at discharge from hospital. Postoperative pathology reported benign insulinoma for all patients. Postoperative complications occurred in 3 patients, including pancreatic fistula (grade A) in 1 patient and rebound hyperglycemia in 2 patients. The length of postoperative hospital stay was 5.0–15.0 d. Follow-up was conducted for 10 to 43 months, and the hypoglycemia symptoms completely disappeared and no tumor recurrence was observed in the 10 patients with complete tumor resection.
Conclusion: Laparoscopic resection is safe, effective and minimally invasive for benign insulinoma located in the surface of pancreatic neck, body or tail and benign insulinoma suitable for pancreatic body and tail resection. So, it is recommended to be used in clinical practice.

10 Emphysematous pancreatitis: a report of three cases and literature review

CAO Lijun , ZHANG Pinjie , HU Qiuyuan , CHEN Hu , SUN Yun

2020, 29(9):1098-1104. DOI: 10.7659/j.issn.1005-6947.2020.09.010

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Background and Aims: Emphysematous pancreatitis (EP) is regarded as a rare form of necrotizing pancreatitis, with a high mortality. However, it has not been definitely classified so far, and also no consensus on its treatment protocol has been reached at home and abroad. Here, the authors summarize the clinical features, pathogenesis, diagnosis and treatment as well as outcomes of 3 cases of EP, so as to provide help for the clinical diagnosis and treatment of this condition in future.
Methods: The clinical data of 3 patients admitted and diagnosed with EP were retrospectively analyzed. The relevant literature was reviewed and discussed.
Results: Case 1 was a 72-year-old male patient who was admitted due to abdominal pain for 12 h and abdominal CT revealed the signs of acute pancreatitis. The patient developed a high-grade fever on the 5th day of admission, and reexamination abdominal CT on the that day showed pancreatic necrosis and diffuse gas shadows in the peripancreatic region, and then, an emergency peripancreatic necrosectomy was performed. Massive retroperitoneal hemorrhage occurred on the 28th day after operation, and the patient was discharged on that day after failure of conservative treatment and died on the same day. Case 2 was a 70-year-old woman who was admitted for severe abdominal pain for 1 d, and presented with septic shock on admission. CT scan on the admission day showed pancreatitis complicated with gas collections in the retroperitoneal space. Emergency laparoscopic exploration and converted open incision of the pancreatic capsule for decompression plus abdominal drainage was performed. The shock status continued to worsen and multiple organ dysfunction appeared which could not be corrected after operation. The patient was discharged on her own request 4 d after operation and died on the same day. Case 3, 71-year-old man, was hospitalized for abdominal pain for 20 h. CT scan showed acute pancreatitis without retroperitoneal gas. On the 9th day of admission, reexamination CT showed blurred contours of the pancreas and gas collections in the peripancreatic region, and percutaneous catheter drainage (PCD) was performed. On the 25th day of admission, massive retroperitoneal hemorrhage occurred, and interventional embolization was performed. One month after admission, laparotomy necrosectomy plus transverse colostomy was performed, and the patients recovered and was discharged from hospital 30 d after surgery. According the literature, the mortality rate of EP reached 10%–36%, and risk factors associated with mortality have not been well summarized. Generally, fulminant type EP was associated with a poor prognosis and subacute type EP had a relatively benign prognosis.
Conclusion: EP is a rare and life-threatening necrotizing infection of the pancreas. CT is the first choice for diagnosis of EP. Regardless of whether for the fulminant type or the subacute type EP, active antimicrobial therapy, early percutaneous catheter drainage and other minimally invasive treatment as well as delayed surgery are helpful to improve the prognosis.

11 Analysis of indications and clinical value of open pancreatic necrosectomy in treatment of infected pancreatic necrosis

NING Caihong , ZHU Shuai , SHEN Dingcheng , CAO Xintong , LIN Jiayan , LI Jiarong , JI Liandong , WEI Wei , HUANG Gengwen

2020, 29(9):1105-1111. DOI: 10.7659/j.issn.1005-6947.2020.09.011

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Background and Aims: With the development of critical care medicine and the update of the surgical concepts and treatment modalities in recent years, the minimally invasive step-up approaches of different types have gradually become the mainstream methods for the treatment of infected pancreatic necrosis (IPN). However, traditional open pancreatic necrosectomy (OPN) still plays an irreplaceable role. This study was conducted to analyze the new characteristics and clinical value of OPN in treatment of IPN in the era of minimally invasive surgery.
Methods: A total of 140 consecutive patients with IPN treated in Xiangya Hospital of Central South University from January 2014 to May 2019 were reviewed. Of the patients, 24 cases underwent OPN and 116 cases were treated with purely minimally invasive approach, and the main attention was focused on the clinical characteristics, surgical timing, indications and outcomes of the 24 cases undergoing OPN. In the whole group of IPN patients, the therapeutic principle of delayed surgery was implemented. For those failed to antibiotic treatment, surgical intervention was performed after full encapsulation and liquefaction of the pancreatic necrosis by prolongation of the conservative treatment as maximal as possible at least 3 to 4 weeks after the onset.
Results: The indications or reasons for OPN in the 24 patients included no route for PCD in one case (4.2%), aggressively performed OPN in 5 cases (20.8%), uncontrollable infection after minimally invasive surgery in 6 cases (25.0%), serious associated complications in 9 cases (37.5%) and uncontrollable infection after open surgery in other hospitals in 3 cases (12.5%). All patients undergoing OPN were complicated with severe retroperitoneal and bloodstream infections, of whom, 79.2% (19/24) were multidrug-resistant infections, 58.3% (14/24) were bloodstream infections, 29.2% (7/24) were peripancreatic fungal infections, and 4.2% (1/24) were fungal bloodstream infection. Klebsiella pneumoniae was the most common microorganism isolated from the peripancreatic necrosis. In patients undergoing OPN compared with patients undergoing purely minimally invasive surgery, the proportion of cases with severe illness was high (87.5% vs. 63.8%), the average length of ICU stay was prolonged (26.9 d vs. 17.7 d), the average length of hospital stay after intervention was shortened (24.1 d vs. 42.9 d), and the mortality rate was increased (45.8% vs. 20.7%), and all the differences had statistical significance (all P<0.05); no significant differences in other general data, the interval between intervention and onset, and the main postoperative complications (massive bleeding, intestinal fistula and pancreatic fistula) were noted (all P>0.05). The main causes for postoperative death in patients undergoing OPN included septic shock in 5 cases (45.5%) and hemorrhagic shock in 6 cases (54.5%).
Conclusion: OPN still plays an irreplaceable role in the treatment of IPN, and sometimes even the only way to save the life of the patients. In the era of minimally invasive surgery, appropriate selection of indications and timing for OPN has great importance in improving the prognosis of the patients with severe acute pancreatitis.

12 Comparison of clinical efficacy between percutaneous nephroscopic and laparoscopic surgery for severe acute pancreatitis with infectious pancreatic necrosis

LI Shaoyi , ZHANG Kunpeng , ZHEN Zhongguang

2020, 29(9):1112-1118. DOI: 10.7659/j.issn.1005-6947.2020.09.012

[Abstract](823) [HTML](875) [PDF 2.80 M](1042)

Abstract:
Background and Aims: At present, the concept of surgical treatment of severe acute pancreatitis (SAP) combined with infectious pancreatic necrosis (IPN) has gone through a transition from the previous early open surgery to the delayed surgery with minimally invasive, step-up approach and adequate drainage. According to this new concept, this study was conducted to compare the clinical efficacy of two minimally invasive surgical methods in treatment of SAP with IPN.
Methods: The clinical data of 53 patients with SAP who developed IPN treated from January 2014 to May 2019 were retrospectively analyzed. Of the patients, 26 cases underwent percutaneous nephroscopic necrosectomy via retroperitoneal approach (percutaneous nephroscopic group) and 27 cases underwent laparoscopic necrosectomy (laparoscopic group). The preoperative general data, main efficacy variables and the changes in infection indexes before and after surgery were compared between the two groups of patients.
Results: There were no significant differences in the general data between the two groups of patients (all P>0.05). Operations were uneventfully completed in all patients, 2 cases in percutaneous nephroscopic group underwent second sinus tract exploration and debridement 2 weeks later under bedside local anesthesia, and 2 cases in laparoscopic group were converted to open surgery. Comparison between percutaneous nephroscopic group and laparoscopic group showed that the average operative time (51.8 min vs. 57.4 min), average intraoperative blood loss (50.2 mL vs. 65.8 mL), average time to postoperative gas passage (21.6 h vs. 22.7 h), average length of postoperative hospital stay (48.5 d vs. 51.2 d), and average hospital cost (82 000 yuan vs. 106 000 yuan) were significantly decreased in the former (all P<0.05). The postoperative drainage volume of patients in both groups were increased compared with those before surgery, and the infection indexes that included the body temperature, white blood cell count, procalcitonin, C-reactive protein, interleukin-6, and score of CT severity index (CTSI) for pancreatitis were all decreased after surgery compared with those before surgery (partial P<0.05), but there were no differences in all above variables between the two groups at the same time point (all P>0.05). The incidence of total postoperative complications such as intestinal fistula, pancreatic fistula, bleeding, pneumonia and pancreatic pseudocyst showed no significant difference between percutaneous nephroscopic group and laparoscopic group (34.6% vs. 37%, P>0.05).
Conclusion: The symptoms of infection and intoxication in patients with SAP and concomitant IPN can be significantly improved by the two treatment methods, and they both have demonstrable efficacy. Compared with laparoscopic surgery, percutaneous nephroscopic procedure has advantages in terms of operative time, blood loss, postoperative recovery and hospitalization cost, without increasing the incidence of complications. So, it is recommended to be used in clinical practice.

13 Analysis of clinical efficacy and indications of ERCP combined with EST for treatment of acute biliary pancreatitis

YANG Wen , LI Xiuhong

2020, 29(9):1119-1125. DOI: 10.7659/j.issn.1005-6947.2020.09.013

[Abstract](232) [HTML](895) [PDF 1.04 M](958)

Abstract:
Background and Aims: Acute biliary pancreatitis (ABP) is a common disease and its most common cause is choledocholithiasis. At present, the mainstream view in China is that endoscopic retrograde cholangiopancreatography (ERCP) combined with endoscopic sphincterotomy (EST) should be performed as early as possible for diagnosis and treatment of the early-onset ABP. However, the recent literature and guidelines demonstrated that ERCP combined with EST are not suitable for all ABP patients. Therefore, concerning this issue, this study was conducted to further investigate the clinical value and clinical indications of ERCP plus EST in treatment of ABP.
Methods: The clinical data of 107 patients admitted for ABP from January 2016 to January 2019 were retro-spectively analyzed. Of the patients, 47 cases underwent conservative treatment, and the other 60 cases received ERCP plus EST within 72 h of admission on the basis of conservative treatment. The clinical efficacy variables of the two treatment methods were compared.
Results: Results of the overall analysis showed that ERCP plus EST was significantly superior to conservative treatment in terms of abdominal pain relief time, CRP recovery time and blood amylase recovery time (all P<0.05). Further subgroup analysis indicated that ERCP plus EST was significantly better than conservative treatment in abdominal pain relief time, leukocyte recovery time, CRP recovery time, blood amylase recovery time and average hospitalization time for ABP patients with concomitant acute cholangitis (all P<0.05), but had no obvious advantages over conservative treatment in each observed variable for ABP patients without acute cholangitis (all P>0.05). In either overall analysis or subgroup analysis, the hospitalization costs of ERCP plus EST were significantly higher than those of conservative treatment (all P<0.05), while no significant differences in the incidence rates of complications were noted between the two treatment methods (all P>0.05).
Conclusion: For ABP, ERCP plus EST has certain advantages over conservative treatment, and especially for ABP with concomitant acute cholangitis, has demonstrable efficacy. However, ERCP plus EST has no sig-nificant superiorities to conservative treatment for ABP without cholangitis, instead it increases the hospitalization costs. Therefore, the patient's condition should be comprehensively analyzed in clinical practice, which cannot be treated uniformly. The individualized treatment plan is recommended.

14 Current status of pancreaticojejunostomy technique for pancreatoduodenectomy and prevention strategies for pancreatic fistula

DENG Hongyang , WEI Fengxian , XU Xiaodong

2020, 29(9):1126-1133. DOI: 10.7659/j.issn.1005-6947.2020.09.014

[Abstract](383) [HTML](1018) [PDF 1.10 M](1167)

Abstract:
Pancreatoduodenectomy (PD) is the standard procedure for the treatment of pancreatic head or periampullary malignancies, and some benign diseases as well as precancerous lesions. Pancreaticojejunostomy-associated postoperative pancreatic fistula (POPF) is one of the important causes for the adverse outcomes of the operation, bringing huge pain and economic loss to the patients and their families. Existing studies suggest that POPF may be the result of multiple factors, and pancreaticojejunostomy is one of the independent risk factors and also one of the important factors that can be controlled by surgeons. However, although there have been more than 100 reported pancreaticoenterostomy methods, POPF cannot be avoided and none of them have been fully recognized. So, pancreatic surgeons are keeping looking for a more reliable anastomosis between the pancreas and intestine. Nowadays, scholars at home and abroad have never stopped exploring pancreaticojejunostomy, and they are also making unremitting efforts in developing other measures to prevent pancreatic fistula. Based on the above background, the authors reviews the current situation of pancreaticojejunostomy and POPF prevention strategies, so as to help reduce the harm of POPF.

15 New research progress of autophagy in acute pancreatitis

ZHOU Jia , MO Mengjun , LIU Sulai , LI Ou , SONG Yinghui , PENG Chuang

2020, 29(9):1134-1140. DOI: 10.7659/j.issn.1005-6947.2020.09.015

[Abstract](641) [HTML](952) [PDF 713.53 K](1109)

Abstract:
Autophagy is a major catabolic process in which cells remove damaged, defective or useless organelles, long-lived proteins and lipids from the cytoplasm, and recycle their components to meet the nutritional and energy needs of biological metabolism. Acute pancreatitis (AP) is a common critical disease, and its prevalence continues to rise in recent years. Studies have demonstrated that autophagy plays an important role in the pathogenesis of AP, it can cause trypsinogen activation and accumulation of large vacuoles in the pancreatic acinar cells, and induce the release of proinflammatory mediators, and thereby cause inflammatory cell infiltration of the pancreas and systemic inflammatory response. Here, the authors address the molecular mechanism of autophagy and the mechanism of autophagy in the occurrence and development of AP.

16 Role of mitochondrial damage in the pathogenesis of acute pancreatitis

WU Yingke , WANG Weixing

2020, 29(9):1141-1146. DOI: 10.7659/j.issn.1005-6947.2020.09.016

[Abstract](479) [HTML](787) [PDF 1.02 M](1197)

Abstract:
Acute pancreatitis (ap) is a serious inflammatory disease, and its pathogenesis is not yet fully elucidated. So, there is no specific treatment for AP in clinical practice. More and more studies have demonstrated that mitochondrial injury is at the center of the pathogenesis of AP. It is currently considered that mitochondrial injury is closely associated with calcium overload, intracellular ATP depletion, changes in mitochondrial membrane permeability, and impaired autophagy. These pathological changes are jointly involved in the occurrence and development of AP. In addition, the regulation of mitochondria on the death pathway of acinar cells also exerts important roles in AP. Here, the authors address the research progress of the pathological mechanism of mitochondrial dysfunction in AP.

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Volume 29,Issue 9,2020 Table of Contents

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