Characterization of Pancreatic Fistula after Post-pancreatectomy Acute Pancreatitis.

OBJECTIVE: This study aimed to investigate the clinical significance and risk factors of postoperative pancreatic fistula (POPF) after post-pancreatectomy acute pancreatitis (PPAP) in patients who underwent pancreaticoduodenectomy (PD). SUMMARY BACKGROUND DATA: PPAP has been recognized as a critical factor in the pathophysiology of POPF after PD. METHODS: A total of 817 consecutive patients who underwent elective PD between January 2020 and June 2022 were included. PPAP and POPF were defined in accordance with the International Study Group for Pancreatic Surgery (ISGPS) definitions. Multivariate logistic analyses were performed to investigate the risk factors for POPF. Comparisons between PPAP-associated POPF and non-PPAP-associated POPF were made to further characterize this intriguing complication. RESULTS: Overall, 159 (19.5%) patients developed POPF after PD, of which 73 (45.9%) occurred following PPAP, and the remaining 86 (54.1%) had non-PPAP-associated POPF. Patients with PPAP-associated POPF experienced significantly higher morbidity than patients without POPF. Multivariate analyses revealed distinct risk factors for each POPF type. For PPAP-associated POPF, independent risk factors included estimated blood loss >200 mL (OR 1.93), MPD ≤3 cm (OR 2.88), and soft pancreatic texture (OR 2.01), largely overlapping with FRS (Fistula Risk Score) elements. On the other hand, non-PPAP-associated POPF was associated with age >65 years (OR 1.95), male (OR 2.10), and MPD ≤3 cm (OR 2.57). Notably, among patients with PPAP, the incidence of POPF consistently hovered around 50% regardless of the FRS stratification. CONCLUSIONS: PPAP-associated POPF presents as a distinct pathophysiology in the development of POPF after PD, potentially opening doors for future prevention strategies targeting the early postoperative period.

The Effect of Perioperative Dexamethasone on Postoperative Complications after Pancreaticoduodenectomy: A Multicenter Randomized Controlled Trial.

OBJECTIVE: This study aimed to evaluate the effect of perioperative dexamethasone on postoperative complications after pancreaticoduodenectomy. BACKGROUND: The glucocorticoid dexamethasone has been shown to improve postoperative outcomes in surgical patients, but its effects on postoperative complications after pancreaticoduodenectomy are unclear. METHODS: This multicenter, double-blind, randomized controlled trial was conducted in four Chinese high-volume pancreatic centers. Adults undergoing elective pancreaticoduodenectomy were randomized to receive either 0.2 mg/kg dexamethasone or a saline placebo as an intravenous bolus within 5 minutes after anesthesia induction. The primary outcome was the Comprehensive Complication Index (CCI) score within 30 days after the operation, analyzed using the modified intention-to-treat principle. RESULTS: Among 428 patients for eligibility, 300 participants were randomized and 265 were included in the modified intention-to-treat analyses. 134 patients received dexamethasone and 131 patients received a placebo. The mean (SD) CCI score was 14.0 (17.5) in the dexamethasone group and 17.9 (20.3) in the placebo group (mean difference, -3.8; 95% CI, -8.4 to 0.7; P=0.100). The incidence of major complications (Clavien-Dindo grade ≥III) (12.7% vs. 16.0%, risk ratio 0.79; 95% CI, 0.44 to 1.43; P=0.439) and postoperative pancreatic fistula (25.4% vs. 31.3%, risk ratio 0.81; 95% CI, 0.55 to 1.19; P=0.286) were not significantly different between the two groups. In the stratum of participants with a main pancreatic duct ≤3 mm (n=202), the CCI score was significantly lower in the dexamethasone group (mean difference, -6.4; 95% CI, -11.2 to -1.6; P=0.009). CONCLUSION: Perioperative dexamethasone did not significantly reduce postoperative complications within 30 days after pancreaticoduodenectomy.

Enhancement pattern of the pancreatic parenchyma predicts postpancreatectomy acute pancreatitis after pancreaticoduodenectomy.

OBJECTIVES: To assess the association between the enhancement pattern of the pancreatic parenchyma on preoperative multiphasic contrast-enhanced computed tomography (CECT) and the occurrence of postpancreatectomy acute pancreatitis (PPAP) after pancreaticoduodenectomy (PD). METHODS: A total of 513 patients who underwent PD were retrospective enrolled. The CT attenuation values of the nonenhanced (N), arterial (A), portal venous (P), and late (L) phases in the pancreatic parenchyma were measured on preoperative multiphasic CECT. The enhancement pattern was quantized by the CT attenuation value ratios in each phase. Receiver operating characteristic (ROC) curve analyses were computed to evaluate predictive performance. Regression analyses were used to identify independent risk factors for PPAP. RESULTS: PPAP developed in 102 patients (19.9%) and was associated with increased morbidity and a worse postoperative course. The A/P ratio, P/L ratio, and A/L ratio were significantly higher in the PPAP group. On the ROC analysis, the A/L ratio and A/P ratio both performed well in predicting PPAP (A/L: AUC = 0.7579; A/P: AUC = 0.7497). On multivariate analyses, the A/L ratio > 1.29 (OR 4.30 95% CI: 2.62-7.06, p < 0.001) and A/P ratio > 1.13 (OR 5.02 95% CI: 2.98-8.45, p < 0.001) were both independent risk factors of PPAP in each model. CONCLUSIONS: The enhancement pattern of the pancreatic parenchyma on multiphasic preoperative CECT is a good predictor of the occurrence of PPAP after PD, which could help clinicians identify high-risk patients or enable selective enhance recovery protocols. CLINICAL RELEVANCE STATEMENT: Preoperative identification of patients at high risk for postpancreatectomy acute pancreatitis by enhancement patterns of the pancreatic parenchyma allows surgeons to tailor their perioperative management and take precautions. KEY POINTS: PPAP is associated with increased risk of postoperative complications and a worse postoperative course. A rapid-decrease enhancement pattern of the pancreatic parenchyma is related to the occurrence of PPAP. The A/L and A/P ratios were both independent risk factors of PPAP in each multivariate model.

Robotic versus open pancreatoduodenectomy in patients with pancreatic duct adenocarcinoma after the learning curve: a propensity score-matched analysis.

BACKGROUND: Studies have demonstrated that the learning curve plays an important role in robotic pancreatoduodenectomy (RPD). Although improved short-term outcomes of RPD after the learning curve have been reported compared to open pancreatoduodenectomy (OPD), there is a lack of long-term survival analyses. METHODS: Patients who underwent curative intended RPD and OPD for pancreatic duct adenocarcinoma (PDAC) between January 2017 and June 2020 were retrospectively reviewed. A 1:2 propensity score matching (PSM) analysis was performed to balance the baseline characteristics between the RPD and OPD groups. RESULTS: Of the 548 patients (108 RPD and 440 OPD), 103 RPD patients were matched with 206 OPD patients after PSM. There were 194 (62.8%) men and 115 (37.2%) women, with a median age of 64 (58-69) years. The median overall survival (OS) in the RPD group was 33.2 months compared with 25.7 months in the OPD group (p = 0.058, log-rank). The median disease-free survival (DFS) following RPD was longer than the OPD (18.5 vs. 14.0 months, p = 0.011, log-rank). The RPD group has a lower incidence of local recurrence compared the OPD group (36.9% vs. 51.2%, p = 0.071). Multivariate Cox analysis demonstrated that RPD was independently associated with improved OS (HR 0.70, 95% CI 0.52-0.94, p = 0.019) and DFS (HR 0.66, 95% CI 0.50-0.88, p = 0.005). CONCLUSION: After the learning curve, RPD had improved oncologic outcomes in PDAC patients compared to OPD. Future prospective randomized clinical trials will be required to validate these findings.

Postpancreatectomy Acute Pancreatitis After Pancreaticoduodenectomy: A Distinct Clinical Entity.

OBJECTIVE: This study aimed to characterize postpancreatectomy acute pancreatitis (PPAP) after pancreaticoduodenectomy (PD) in a high-volume center. BACKGROUND: The International Study Group for Pancreatic Surgery (ISGPS) has recently proposed a new definition and grading scale of PPAP, but specific studies are lacking. METHODS: Patients who underwent PD from 2020 to 2021 were retrospectively reviewed. PPAP was defined based on the International Study Group for Pancreatic Surgery definition: sustained elevation of serum amylase levels for least the first 48 hours postoperatively and radiologic alterations consistent with PPAP. RESULTS: Among a total of 716 patients who were finally analyzed, PPAP occurred in 152 (21.2%) patients. Patients with PPAP were associated with significantly higher incidences of postoperative pancreatic fistula (POPF) (40.8% vs 11.7%, P <0.001), major complications (13.8% vs 6.6%, P =0.004), and biliary leak (11.8% vs 4.6%, P =0.001). Among them, 8 patients developed grade C PPAP leading to organ failure, reoperation, or death. Patients developing PPAP alone also demonstrated a statistically significantly increased rate of major complications than those without PPAP or POPF. In contrast, no differences were found in postoperative outcomes in patients with POPF in terms of whether they were associated with PPAP. CONCLUSION: PPAP is a distinct complication after PD with distinctive clinical outcomes. A part of PPAP presents as an inflammatory process in the early postoperative period but sometimes could lead to necrotizing pancreatitis or other severe clinical scenarios, and another part of PPAP would lead to anastomotic failure that accounts for a great proportion of POPF occurrence.

The Impact of Additional Para-aortic Dissection During Pancreaticoduodenectomy for Resectable Pancreatic Cancer.

BACKGROUND: The short-term outcome and long-term survival of pancreaticoduodenectomy with additional para-aortic dissection (PAD) for patients with resectable pancreatic cancer remain obscure. PATIENTS AND METHODS: Consecutive patients who underwent radical pancreaticoduodenectomy for resectable pancreatic cancer in a single high-volume center during a 7-year period were included retrospectively. Both short- and long-term effects of PAD were compared between the PAD group and the no PAD group. Then, the PAD group was divided into the non-metastatic para-aortic lymph node (PALN-) group and the metastatic PALN (PALN+) group to further analyze the prognosis of PALN+. RESULTS: Of the 909 included patients, 280 (30.8%) underwent PAD during pancreaticoduodenectomy. The PAD group had a higher rate of intra-abdominal infection compared with the no PAD group (28.6% vs. 20.7%, P = 0.009) but no differences were found in the incidence of other complications. The overall survival (OS) and recurrence-free survival (RFS) were also comparable between the two groups. Subgroup analysis showed that patients with PALN+ had a worse OS than patients in the PALN- group (median of 14 vs. 20 months, P = 0.048). Multivariate Cox regression analysis further revealed that PALN+ was an independent adverse predictor of OS (hazard ratio: 1.70, P = 0.007). CONCLUSIONS: This study suggests that the addition of PAD during pancreaticoduodenectomy does not improve the prognosis of patients with resectable pancreatic cancer and may lead to an increased risk of infection. However, the accurate preoperative assessment and appropriate treatment strategy for patients with PALN+ need further investigation due to the poor prognosis.

Impact of the transection plan on postoperative pancreatic fistulas occurring after robot-assisted distal pancreatectomy for nonmalignant pancreatic neoplasms.

OBJECTIVES: Postoperative pancreatic fistula (POPF) is the main complication of distal pancreatectomy (DP) and affects the prognosis of patients. The impact of several clinical factors mentioned in recent studies on POPF remains controversial. This study aimed to investigate the impact of a remnant pancreas and other perioperative factors on POPFs occurring after robot-assisted distal pancreatectomy (RDP) for nonmalignant pancreatic neoplasms. METHODS: A total of 197 patients who received robot-assisted distal pancreatectomy (RDP) for nonmalignant pancreatic neoplasms at the Pancreatic Disease Center, Ruijin Hospital Shanghai Jiaotong University School of Medicine from January 2018 to December 2020 were included in this retrospective study. According to the intraoperative transection plan, patients were divided into an RDP body group and an RDP tail group. Clinical and pathological features and perioperative factors affecting POPF were analyzed and compared between the two groups. RESULTS: The results showed that a transection plan involving the tail of the pancreas (OR = 2.133, 95% CI 1.109-4.103, p = 0.023) and spleen preservation (OR = 2.588, 95% CI 1.435-4.665, p = 0.001) independently increased the incidence of POPF in patients with nonmalignant pancreatic neoplasms treated by RDP. A transection plan involving the tail of the pancreas was also an independent risk factor (OR = 3.464, 95% CI 1.270-9.450, p = 0.015) for grade B/C POPF. Length of remnant pancreas > 6.23 cm was an independent risk factor for POPF (OR = 3.116, 95% CI 1.364-7.121, p = 0.007). Length of remnant pancreas > 9.82 cm was an independent risk factor for grade B/C POPF (OR = 3.340, 95% CI 1.386-8.051, p = 0.007). CONCLUSION: This retrospective study suggests that a transection plan involving the tail of the pancreas is an independent risk factor for POPF in patients with nonmalignant neoplasms treated by RDP. We also propose that the postoperative length of the remnant pancreas evaluated by computed tomography scans can be used to identify patients with a high risk of POPF in order to optimize the individualized strategy.

Hypoxia-induced long non-coding RNA LINC00460 promotes p53 mediated proliferation and metastasis of pancreatic cancer by regulating the miR-4689/UBE2V1 axis and sequestering USP10.

Long non-coding RNAs are considered to be key regulatory factors of oncogenesis and tumor progression. It is reported that LINC00460 plays the role of oncogene in some tumors. However, LINC00460's role and mechanism of action in pancreatic cancer have not yet been fully elucidated. We identified LINC00460 by analyzing data from the Gene Expression Omnibus database. The role of LINC00460 in proliferation and metastasis was examined using CCK8, colony formation, wound healing, and transwell assays. The potential mechanisms of LINC00460 in regulating mRNA levels were elucidated by RNA pull-down, RNA immunoprecipitation, Chromatin immunoprecipitation, Co-immunoprecipitation, and Immunofluorescence assays. The results showed that LINC00460 was upregulated in pancreatic cancer cells and tissues. Highly expressed LINC00460 is significantly related to short survival of pancreatic cancer patients. Inhibition of LINC00460 attenuated pancreatic cancer cell proliferation and metastasis, whereas its overexpression reversed this effect. Mechanically, LINC00460 is induced by hypoxia, through binding of the hypoxia-inducible factor 1-α in the promoter region of LINC00460. Furthermore, LINC00460 functioned as an miR-4689 sponge to regulate the downstream target gene UBE2V1, enhancing the stability of mutant p53 in pancreatic cancer cells. LINC00460 also further promotes pancreatic cancer development by sequestering USP10, a cytoplasmic ubiquitin-specific protease that deubiquitinates p53 and enhances its stability. Collectively, our study demonstrated that LINC00460 is a hypoxia-induced lncRNA that plays the role of oncogene in pancreatic cancer by modulating the miR-4689/UBE2V1 axis, sequestering USP10, and ultimately enhancing the stability of mutant p53.

A Novel Criterion for Lymph Nodes Dissection in Distal Pancreatectomy for Ductal Adenocarcinoma: A Population Study of the US SEER Database.

OBJECTIVE: The aim of this study was to clarify the minimum number of examined lymph nodes (MNELNs) required to ensure the quality of lymph node detection and its impact on long-term survival in distal pancreatectomy for pancreatic ductal adenocarcinoma. METHODS: Clinicopathological characteristics and survival data of patients with resectable pancreatic cancer who underwent distal pancreatectomy between 2004 and 2017 were collected from the Surveillance, Epidemiology, and End Results database. The associations between the number of examined lymph nodes (ELNs) and number of positive lymph nodes (PLNs), stage migration, and overall survival were investigated through adjusted multivariate models with locally weighted scatterplot smoothing smoothing fitting curves and estimation of the structural breakpoints. Kaplan-Meier survival analysis and X-tile software were used to identify the ideal cut-off value for ELNs. RESULTS: In total, 2610 consecutive patients who underwent distal pancreatectomy between 2004 and 2017 were included in this study. The optimal ELN count according to the associations between the number of ELNs and number of PLNs, odds ratio for stage migration, or hazard ratio for overall survival were 19, 17, and 19, respectively. Furthermore, the optimal division of ELN count for maximum overall survival was divided into three populations (ELN ≤ 8, ELN 9-18, ELN ≥ 19) based on X-tile software. CONCLUSION: A minimal count of 19 lymph nodes was demanded to guarantee the quality of lymph node examination in patients with distal pancreatectomy. Long-term survival could be delimited by MNELNs. A sufficient number of ELNs could improve the accuracy of cancer staging and reflect a better overall survival.

Serum lipase on postoperative day one is a strong predictor of clinically relevant pancreatic fistula after pancreaticoduodenectomy: A retrospective cohort.

BACKGROUND: Increased postoperative serum amylase has been recently reported to be associated with increased postoperative morbidity, but studies on postoperative serum lipase are limited. The aim of this study was to evaluate the value of postoperative serum lipase in predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). METHOD: A retrospective analysis was performed on 212 patients who underwent PD from September 2018 and March 2021, focusing on the association between postoperative day (POD) 1 serum lipase and CR-POPF. RESULTS: Overall, 108 (50.9%) patients had elevated serum lipase levels (>68 U/L) on POD 1. Patients with elevated serum lipase exhibited a significantly higher incidence of CR-POPF (37.0% vs. 6.7%, p < 0.001). Receiver operating characteristic (ROC) analyses showed improved diagnostic accuracy for POD 1 serum lipase compared with POD 1 serum amylase in predicting CR-POPF (AUC: 0.801 vs. 0.745, p = 0.029). Elevated serum lipase on POD 1 and elevated serum CRP on POD 3 were identified as independent predictors of CR-POPF. A simple early postoperative model, consisting of POD 1 serum lipase levels and POD 3 serum CRP levels, showed good discrimination (AUC 0.76, 95% CI 0.69-0.83) to identify the onset of CR-POPF. CONCLUSION: Serum lipase on POD 1 outperformed serum amylase on POD 1 in predicting CR-POPF after PD. The combination of POD 1 serum lipase and POD 3 serum CRP provides a reliable predicting model for CR-POPF.

TNFAIP3 Mediated by Novel Nano Composite Adsorbent on Tumor Necrosis Factor-α in Rats with Lumbar Disc Herniation by Inhibiting NF-κB Pathway.

Mobile phones and computers have been widely used in the work of people. The incidence rate of lumbar disc herniation(LDH) has gradually increased and the trend toward younger age has been increasing. According to the epidemiological survey, about half of people will experience lumbar pain in their life and the resulting huge social and economic burden. It has important clinical significance for the treatment of lumbar disc herniation of TNFaIP3 mediated by a new nanocomposite adsorbent on tumor necrosis factor(TNF)- in rats with LDH by inhibiting the  pathway. This paper mainly studies the mechanism and efficacy of TNFaIP3 mediated by a new nanocomposite adsorbent on TNF- in rats with LDH by inhibiting the  pathway. Eight groups of human nucleus pulposus cells were randomly divided into four groups: high inhibition group, medium inhibition group, low inhibition group and no inhibition group. After interfering with human nucleus pulposus cells by inhibiting the  pathway, the cells were allowed to stand for 24 hours to extract and detect TNF-, p-p65, P50, IKB and IKK in the  signaling pathway to explore the mechanism of inhibiting  pathway on TNF- in rats with LDH. The experimental results showed that after 24 hours of intervention, compared with the non-inhibition group, the expression of TNF in the low inhibition group, medium inhibition group and high inhibition group decreased relatively, and with the increase of inhibition degree, the expression of TNF in each group decreased more obviously, such as the expression of TNF in non-inhibition group was 1.48, the expression of TNF in low inhibition group was 1.31, the expression of TNF in medium inhibition group was 0.74, and the expression of TNF in high inhibition group was 0.58. The expression of P50 was 1.86 in non-inhibition, 1.47 in low inhibition, 1.32 in medium inhibition and 1.13 in high inhibition.

Learning Curve From 450 Cases of Robot-Assisted Pancreaticoduocectomy in a High-Volume Pancreatic Center: Optimization of Operative Procedure and a Retrospective Study.

OBJECTIVE: We aimed to describe our experience and the learning curve of 450 cases of robot-assisted pancreaticoduodenectomy (RPD) and optimize the surgical process so that our findings can be useful for surgeons starting to perform RPD. SUMMARY BACKGROUND DATA: Robotic surgical systems were first introduced 20 years ago. Pancreaticoduodenectomy (PD) is a challenging surgery because of its technical difficulty. RPD may overcome some of these difficulties. METHODS: The medical records of 450 patients who underwent RPD between May 2010 and December 2018 at the Shanghai Ruijin Hospital were retrospectively analyzed. Operative times and estimated blood loss (EBL) were analyzed and the learning curve was determined. A cumulative sum (CUSUM) analysis was used to identify the inflexion points. Other postoperative outcomes, postoperative complications, and long-term follow-up were also analyzed. RESULTS: Operative time improved graduallyovertimefrom405.4 ±â€Š112.9 minutes (case 1-50) to 273.6 ±â€Š70 minutes (case 301-350) (P < 0.001). EBL improved from 410 ±â€Š563.5 mL (case 1-50) to 149.0 ±â€Š103.3 mL (case 351-400) (P< 0.001). According to the CUSUM curve, there were 3 phases in the RPD learning curve. The inflexion points were around cases 100 and 250. The incidence of pancreatic leak in the last 350 cases was significantly lower than that in the first 100 cases (30.0% vs 15.1%, P = 0.003). CONCLUSIONS: RPD is safe and feasible for selected patients. Operative and oncologic outcomes were much improved after experience of 250 cases. Our optimization of the surgical process may have also contributed to this. Future prospective and randomized studies are needed to confirm our results.

Original study: The rescue staging for pancreatic ductal adenocarcinoma with inadequate examined lymph nodes.

BACKGROUND: In previous studies, it's recommended that the lymph node involvement should be evaluated with enough examined lymph nodes (eLNs) in the 8th American Joint Committee on Cancer (AJCC) staging system for pancreatic cancer. This study aims to put forward a rescue staging system for pancreatic ductal adenocarcinoma (PDAC) patients with inadequate eLNs after pancreatoduodenectomy (PD). METHOD: 11,224 PDAC patients undergoing PD in The Surveillance, Epidemiology, and End Results (SEER) database were included. Another Ruijin Pancreatic Disease Center (RJPDC) database consisted of 821 patients was utilized for external validation. RESULTS: The proportions of patients with eLNs≥15 were 44.7% and 32.8% in SEER and RJPDC database separately. The rescue staging system was put forward relying on LNR (HR = 1.83, 95% CI 1.74-1.92, P < 0.001) for N staging of eLNs<15 population and pLNs for the rest. The TNM modalities were also rearranged in the rescue system for better survival coordination. The C-index of rescue staging system was 0.638 while that of AJCC 8th staging system was 0.613 in SEER database. Similar phenomena were observed in RJPDC database. Kaplan-Meier analyses revealed reliable internal coherences (SEER: Ib: P = 0.26; IIa: P = 0.063; IIb: P = 0.53; IIIa: P = 0.11. RJPDC: Ib: P = 0.32; IIa: P = 0.66; IIb: P = 0.76; IIIa: P = 0.66) and significant staging efficiency (SEER: P < 0.001; RJPDC: P = 0.002). CONCLUSION: A rescue staging system was put forward regardless of the eLNs number. And the novel system manifested better predictive capacity than 8th AJCC staging system.

Preoperative biliary drainage of severely obstructive jaundiced patients decreases overall postoperative complications after pancreaticoduodenectomy: A retrospective and propensity score-matched analysis.

OBJECTIVES: The influence of preoperative biliary drainage (PBD) for obstructive jaundiced patients before pancreaticoduodenectomy is debated in the past decades. The aim of this study is to assess the impact of preoperative biliary drainage on intraoperative and postoperative outcomes in patients with severely obstructive jaundice. METHODS: Data were collected retrospectively from severely obstructive jaundiced patients with serum total bilirubin level exceeding 250 µmol/L and undergoing pancreaticoduodenectomy from January 2012 to December 2017. The univariate and multivariate analyses were performed to assess independent risk factors for overall postoperative complications. A propensity score-matched (PSM) analysis was performed to adjust baseline characteristics between PBD and direct surgery (DS) groups. After PSM, intraoperative data and postoperative complications were compared between the two groups. RESULTS: A total of 200 patients were included. The rate of overall postoperative complication occurred in 119 (59.5%) patients, with prealbumin <150 mg/L (OR = 3.03; 95%CI = [1.63-5.62]; p < 0.001), ASA (American Society of Anesthesiology score) classification II-III (OR = 2.27; 95%CI = [1.21-4.27]; p = 0.011), and direct surgery (OR = 3.88; 95%CI = [1.67-8.99]; p = 0.002) identified as independent risk factors in multivariate analysis. After PSM, there was similar operative time and intraoperative transfusion between PBD and DS group. However, DS group had a higher incidence of overall postoperative complication (p = 0.005), grades B and C of post-pancreatectomy hemorrhage (PPH) (p = 0.032), and grades B and C of postoperative pancreatic fistula (POPF) (p = 0.045) compared to PBD group. CONCLUSIONS: In this retrospective study, in order to reduce overall postoperative complications, PBD should be performed routinely for those patients with serum total bilirubin level exceeding 250 µmol/L and undergoing pancreaticoduodenectomy.

Predictive factors for postoperative pancreatitis after pancreaticoduodenectomy: A single-center retrospective analysis of 1465 patients.

BACKGROUND: Postoperative acute pancreatitis (POAP) after pancreaticoduodenectomy (PD) has been recently recognized as an independent complication that is associated with undesirable postoperative outcomes and often precedes other complications, yet predictive factors attributable to POAP after PD remain elusive. METHODS: The data from 1465 consecutive patients who underwent laparotomy or minimally invasive robotic PD from March 2010 to December 2018 were retrospectively reviewed. POAP was defined as an elevation of the serum amylase levels above the institution's normal upper limit (100 U/L) on postoperative day (POD) 1. Univariate and multivariate analyses were performed to investigate the predictive factors for POAP after PD and the association between POAP and clinically relevant postoperative pancreatic fistulas (CR-POPFs). RESULTS: Among the 1465 patients, 411 (28%) underwent minimally invasive robotic surgeries, and the overall POAP and CR-POPFs rates were 770 (53%) and 277 (19%), respectively. The female sex (OR 1.76), a normal bilirubin level (OR 1.55), the robotic surgery (OR 1.36), a main pancreatic duct (MPD) ≤3 mm (OR 5.69) and a high-risk nonadenocarcinoma pathology (cystic disease: OR 4.33; pNETs: OR 4.34; others: OR 2.74) were considered independent risk factors for POAP. A nondilated MPD was a predominant predictor for POAP, with 72.2% sensitivity and 71.8% specificity. POAP was also an independent predictive factor for CR-POPFs (OR 3.48). CONCLUSION: A nondilated MPD, a high-risk pathology, the female sex, a normal bilirubin level and the robotic surgery were independent predictive factors for POAP after PD. Prevention and early treatment strategy changes can be made based on these preoperative predictive factors.

Higher body mass index deteriorates postoperative outcomes of pancreaticoduodenectomy.

BACKGROUND: Previous studies presented controversies in impact of body mass index (BMI) on perioperative complications in pancreatectomy, and mainly focused on Western population. This study aimed to explore the impact of BMI on perioperative outcomes in Chinese patients undergoing pancreaticoduodenectomy. METHODS: Seven hundred and seven adult patients undergoing open pancreaticoduodenectomy between January 2005 and December 2016 at Ruijin Hospital were studied retrospectively and categorized as obese (BMI ≥25 kg/m2), overweight (BMI ≥23 kg/m2 and <25 kg/m2), or normal weight (BMI ≥18.5 kg/m2 and <23 kg/m2). Associations of these BMI groups with perioperative outcomes were evaluated. RESULTS: The overweight and obese groups experienced higher risk of clinically related postoperative pancreatic fistula (CR-POPF) (7.6% vs. 9.9% vs. 17.6%, P = 0.002) and re-operation (1.1% vs. 2.5%  vs. 5.1%, P = 0.017), and longer systemic inflammation response syndrome (SIRS) duration [2 (1-9) d vs. 2 (1-7) d vs. 3 (1-10) d, P = 0.003] and postoperative hospital stay [19 (2-84) d vs. 19 (7-158) d vs. 23 (8-121) d, P = 0.023] than the normal weight group did. The multiple logistic regression models showed obese as an independent risk factor for CR-POPF (P = 0.013). The multiple linear regression analysis confirmed BMI as a predictor for prolonged postoperative hospital stay (P = 0.005). CONCLUSIONS: Higher BMI results in higher morbidity of Chinese patients undergoing open pancreaticoduodenectomy. Pancreaticoduodenectomy is still a safe surgery procedure for overweight and obese patients, with intensive perioperative management.

Long noncoding RNA NORAD, a novel competing endogenous RNA, enhances the hypoxia-induced epithelial-mesenchymal transition to promote metastasis in pancreatic cancer.

BACKGROUND: Pancreatic cancer, one of the top two most fatal cancers, is characterized by a desmoplastic reaction that creates a dense microenvironment, promoting hypoxia and inducing the epithelial-to-mesenchymal transition (EMT) to facilitate invasion and metastasis. Recent evidence indicates that the long noncoding RNA NORAD may be a potential oncogenic gene and that this lncRNA is significantly upregulated during hypoxia. However, the overall biological role and clinical significance of NORAD remains largely unknown. METHODS: NORAD expression was measured in 33 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of NORAD on pancreatic cancer cells were studied by overexpression and knockdown in vitro. Insights into the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatics analyses and luciferase assays. In vivo, metastatic potential was identified using an orthotopic model of PDAC and quantified using bioluminescent signals. Alterations in RhoA expression and EMT levels were identified and verified by immunohistochemistry and Western blotting. RESULTS: NORAD is highly expressed in pancreatic cancer tissues and upregulated in hypoxic conditions. NORAD upregulation is correlated with shorter overall survival in pancreatic cancer patients. Furthermore, NORAD overexpression promoted the migration and invasion of pancreatic carcinoma cells, while NORAD depletion inhibited EMT and metastasis in vitro and in vivo. In particular, NORAD may function as a ceRNA to regulate the expression of the small GTP binding protein RhoA through competition for hsa-miR-125a-3p, thereby promoting EMT. CONCLUSIONS: Elevated expression of NORAD in pancreatic cancer tissues is linked to poor prognosis and may confer a malignant phenotype upon tumor cells. NORAD may function as a ceRNA to regulate the expression of the small GTP binding protein RhoA through competition for hsa-miR-125a-3p. This finding may contribute to a better understanding of the role played by lncRNAs in hypoxia-induced EMT and provide a potential novel diagnostic and therapeutic target for pancreatic cancer.