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Purpose: This study was designed to assess the uptake heterogeneity in neuroendocrine tumor (NET) patients at initial diagnosis with dual-tracer PET imaging and the staging changes and prognostic value it brings to explore the indication of the use of dual-tracer PET., Methods: Fifty-one newly diagnosed patients with pathologically confirmed NET who underwent 18 F-FDG and 68 Ga-DOTATATE PET imaging between January 2020 and September 2022 were enrolled. Dual-tracer uptake patterns were classified into 3 groups: A. 68 Ga-DOTATATE positive and 18 F-FDG negative, B. 68 Ga-DOTATATE positive and 18 F-FDG positive, and C. 68 Ga-DOTATATE negative and 18 F-FDG positive. Descriptive statistics were used to evaluate the heterogeneity of dual-tracer uptake patterns among different grading (G) groups, between primary and metastatic lesions, and staging changes. Moreover, dual-tracer uptake patterns, grade, age, sex, and stage were compared with progression-free survival (PFS) by Cox regression., Results: In the different G groups, none of the patients with dual-tracer uptake pattern A had grade 3 histology, but 57% of patients with grade 1 disease had FDG avidity (25% of them resulting in dual-tracer uptake pattern C). Patients with no metastasis were well differentiated, but one of them presented with dual-tracer uptake pattern C. Different uptake patterns were also observed between primary and metastatic lesions, particularly 44% of patients with dual-tracer uptake pattern A of primary with FDG avidity of metastases. Moreover, 9 (17.6%) had new lesions detected by additional 18 F-FDG PET imaging, and 3 of them (5.9%) had clinical stage changed accordingly. The Cox regression test showed that the dual-tracer uptake patterns were significantly correlated with PFS by univariate and multivariate analyses ( P = 0.026 and 0.039, respectively), whereas the grade and stage did not correlate with survival (all P >0.05)., Conclusion: The current study has proven the uptake heterogeneity of the NET at initial diagnosis and demonstrated the staging and prognostic value of dual-tracer PET imaging. Our preliminary results have confirmed the importance of dual-tracer imaging modalities and concluded that dual-tracer PET imaging could be considered as prognostic tool for all patients with an initial diagnosis of NET., Competing Interests: Conflicts of interest and sources of funding: none declared. This study was supported by the National Natural Science Foundation of China (grant 81971653) and the “1.3.5” Project for Disciplines of Excellence, West China Hospital, Sichuan University (grant ZYJC21063)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To define the prognostic role of lymph node involvement (LNI) in patients with pancreatic neuroendocrine tumors (PNETs) and identify predictors of LNI using a comprehensive multifactor analysis focusing on preoperative radiological features., Methods: This study included 236 patients with preoperative computed tomography who underwent radical surgical resection of PNETs at our hospital between 2009 and 2019. Univariate and multivariable logistic regression analyses were performed to investigate the risk factors associated with LNI and tumor recurrence. The disease-free survival (DFS) rates with and without LNI were compared., Results: Forty-four of the 236 patients (18.6%) had LNI. Biliopancreatic duct dilatation (odds ratio [OR], 2.295; 95% confidence interval [CI], 1.046-5.035; p = 0.038), tumor margin (OR, 2.189; 95% CI, 1.034-4.632; p = 0.041), and WHO grade (G2: OR, 2.923; 95% CI, 1.005-8.507; p = 0.049; G3: OR, 12.067; 95% CI, 3.057-47.629; p < 0.001) were independent risk factors of LNI in PNETs. Multivariable analysis showed that LNI (OR, 2.728; 95% CI, 1.070-6.954; p = 0.036), G3 (OR, 4.894; 95% CI, 1.047-22.866; p = 0.044), and biliopancreatic duct dilatation (OR, 2.895; 95% CI, 1.124-7.458; p = 0.028) were associated with PNET recurrence in patients after surgery. Patients with LNI had a significantly worse DFS than those without LNI (3-year DFS: 85.9 vs. 96.7%; p < 0.001; 5-year DFS: 65.1 vs. 93.9%; p < 0.001)., Conclusion: LNI was associated with decreased DFS. Biliopancreatic duct dilatation, irregular tumor margins, and grades G2 and G3 were independent risk factors for LNI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Both cachexia and sarcopenia have been considered adverse predictors for prognosis in patients with pancreatic cancer; although sarcopenia and cachexia share some similarities, they are still defined as distinct nutritional conditions. We aimed to explore the differential impacts of sarcopenia and cachexia on prognosis for pancreatic ductal adenocarcinoma (PDAC) patients following radical excision., Methods: From January 2015 to May 2022, 614 patients undergoing surgery for PDAC were retrospectively included. Sarcopenia was defined as the L3 total skeletal muscle index below 52.4 cm 2 /m 2 (men) and 38.5 cm 2 /m 2 (women). Cachexia was classified according to the following criteria: involuntary weight loss >5% over the past 6 months, or weight loss >2% and BMI <20 kg/m 2 , or weight loss >2% and sarcopenia., Results: Of the 614 patients included in the analysis, 62% and 48% were diagnosed with sarcopenia and cachexia, respectively. Kaplan-Meier analysis showed that sarcopenia and/or cachexia were significantly associated with worse overall survival (OS) rather than worse recurrence-free survival (RFS). Moreover, Cox regression analysis revealed that cachexia rather than sarcopenia was an adverse factor for OS in all PDAC patients. For poorly differentiated PDAC, both cachexia and sarcopenia were significantly associated with shorter OS. However, for moderately/well-differentiated PADC, cachexia was an independent factor for adverse OS, but not sarcopenia., Conclusions: Sarcopenia and cachexia have different effects on OS for PDAC patients undergoing radical excision. This difference may provide some important information for preoperative management., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

For typical biodegradable polymers, their overall performance almost declines exponentially to the degradation degree, which inevitably leads to a dilemma between the requirements of service life and retention time in the environment (both in vitro and in vivo ). It is a great challenge to develop a biodegradable polymeric device with relatively stable performance in service while rapidly degrading out of service. Herein, we demonstrate an effective strategy to control degradation of biodegradable polymers in stages by constructing separated bicontinuous microphases with very different microphase degradation rates. First, polyurethane copolymers (PCL-b-CrP-U) containing two blocks, i.e. , semicrystalline poly(ε-caprolactone) (PCL) blocks and amorphous random copolymer blocks (CrP) based on ε-CL and p -dioxanone (PDO), were synthesized. The microscopic morphology of PCL-b-CrP-U is investigated by an alkali-accelerated degradation experiment, which also demonstrates that the chain cleavage-induced crystallization during degradation resulted in a self-reinforcement by forming degradation residues with a scaffold-like morphology. The tensile test shows that PCL-b-CrP-U has excellent mechanical properties (1500% of elongation at break, a tensile strength of about 7.5 MPa, and an elastic modulus of 40.0 MPa). The degradation experiments with artificial pancreatic juice as a working medium reveal that PCL-b-CrP-U samples containing relatively high PDO units exhibit a three-stage degradation, i.e. an induction stage, a steady degradation stage and an accelerated degradation stage. The CrP phase preferentially hydrolyzes to form some microchannels due to its amorphous nature and relatively high hydrophilicity, effectively accelerating the entry of water and enzymes into the inner parts of the sample. Meanwhile, at this stage, those originally amorphous PCL segments gradually crystalize owing to their enhanced chain mobility induced by the chain cleavage, forming a "scaffold"-like structure, which effectively reinforces the sample to resist the damage from external force and therefore guarantees a relatively stable mechanical performance of PCL- b -CrP-U during service. With the further depletion of the CrP phase, the intermediate "scaffold"-like structure is also very beneficial to accelerate the degradation of residues owing to its large specific surface area, which is expected to be beneficial for preventing long-term retention of the implantation devices.

Background: Pancreatic neuroendocrine tumors (pNETs) are heterogenous neoplasms, of which the prognosis varies widely. Purely cystic pancreatic neuroendocrine tumors (C-pNETs) are a small subset of pNETs in which data are extremely rare. This study aimed to compare clinicopathological and long-term survival differences between C-pNETs and solid pNETs (S-pNETs)., Methods: A retrospective review of 242 patients with pNETs underwent resection in our institution from 2009 to 2019 was conducted. Demography characteristics, clinicopathological features and long-term outcomes of them were analyzed., Results: Sixteen out of 242 patients (6.6%) were identified as C-pNETs. Compared with S-pNETs, C-pNETs were more frequently non-functional (75% vs 45%, P = 0.02), and the median tumor diameter of C-pNETs was smaller (36 mm vs. 47 mm, P = 0.001). And the accuracy of preoperative diagnosis of C-pNETs was significantly lower (31% vs 78%, P = 0.001). Of note, the majority of C-pNETs were well-differentiated with G1 (81% vs 35%, P = 0.001). And there were no G3 (0 vs 7%, P = 0.001) in C-pNETs. No T4 stage or R1/R2 surgical margin detected in C-pNETs. And only one C-pNETs (6%) had regional lymph node metastasis (N) or synchronous distant metastasis (M). Additionally, only one patient with C-pNETs (6%) suffered tumor recurrence, compared with 24 (13%) for S-pNETs. And survival analysis showed the patients with C-pNETs seemed to be with better disease-free survival (P = 0.26)., Conclusion: C-pNETs are rare subtype with possibly less aggressive behavior comparing with their solid counterparts. Recurrence and tumor-related death still occurs in patients with resected C-pNETs, although they tend to be with more favorable prognosis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Backgroud: Tumor grade is the determinant of the biological aggressiveness of pancreatic neuroendocrine tumors (PNETs) and the best current tool to help establish individualized therapeutic strategies. A noninvasive way to accurately predict the histology grade of PNETs preoperatively is urgently needed and extremely limited., Methods: The models training and the construction of the radiomic signature were carried out separately in three-phase (plain, arterial, and venous) CT. Mann-Whitney U test and least absolute shrinkage and selection operator (LASSO) were applied for feature preselection and radiomic signature construction. SVM-linear models were trained by incorporating the radiomic signature with clinical characteristics. An optimal model was then chosen to build a nomogram., Results: A total of 139 PNETs (including 83 in the training set and 56 in the independent validation set) were included in the present study. We build a model based on an eight-feature radiomic signature (group 1) to stratify PNET patients into grades 1 and 2/3 groups with an AUC of 0.911 (95% confidence intervals (CI), 0.908-0.914) and 0.837 (95% CI, 0.827-0.847) in the training and validation cohorts, respectively. The nomogram combining the radiomic signature of plain-phase CT with T stage and dilated main pancreatic duct (MPD)/bile duct (BD) (group 2) showed the best performance (training set: AUC = 0.919, 95% CI = 0.916-0.922; validation set: AUC = 0.875, 95% CI = 0.867-0.883)., Conclusions: Our developed nomogram that integrates radiomic signature with clinical characteristics could be useful in predicting grades 1 and 2/3 PNETs preoperatively with powerful capability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Qiu, Tan, Chen, Tan, Ren, Yang, Yao, Cao, Ke and Liu.)

Background: Liver metastases (LMs) are common in advanced pancreatic neuroendocrine tumor (PNET) patients. Currently, the benefit of primary tumor resection (PTR) in the setting of PNET patients with liver metastases is still controversial in several guidelines., Methods: Data were extracted from the Surveillance, Epidemiology and End Results (SEER) database to evaluate this issue. The main index of interest in our study was overall survival time., Results: Information on 536 PNET patients with liver metastases from the SEER database was identified. A total of 214 patients (PTR group) received primary tumor resection, and more than half of them (132 patients) had synchronous LM resection. The other 322 PNET patients (non-PTR group) with liver metastases did not receive primary tumor resection. A significant survival benefit was gained from PTR when compared with non-PTR patients, both in OS (72.93 ± 2.7 vs . 36.80 ± 2.22 months) and 3- or 5-year survival rates (75.1% vs . 28.9% and 67.9% vs . 22.3%, respectively). No difference was found between PTR alone and PTR with synchronous LM resection. From univariate and multivariate analyses, younger age (<65 years) and good or moderate tumor differentiation may be more important when considering primary tumor resection. However, we found that all grades of tumor differentiation could result in a better overall survival time after primary tumor resection., Conclusion: Our study suggested that primary tumor resection in pancreatic neuroendocrine patients with liver metastases could result in a longer survival time. Primary tumor resection with synchronous liver metastasis resection was not related to a better survival benefit. This treatment strategy may routinely be taken into consideration in these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mou, Wang, Tan, Chen, Liu and Ke.)

Histologically, the World Health Organization has classified pancreatic neuroendocrine neoplasms (p-NENs) into well-differentiated pancreatic neuroendocrine tumors (G1/G2 p-NETs) and poorly-differentiated pancreatic neuroendocrine carcinoma (G3 p-NECs) based on tumor mitotic counts and Ki-67 index. Recently, the 8th edition of American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging manual has incorporated some major changes in 2017 that the TNM staging system for p-NENs should only be applied to well-differentiated G1/G2 p-NETs, while poorly-differentiated G3 p-NECs be classified according to the new system for pancreatic exocrine adenocarcinomas. However, this new manual for p-NENs has seldom been evaluated.Data of patients with both G1/G2 and G3 non-functional p-NENs (NF-p-NENs) from our institution was retrospectively collected and analyzed using 2 new AJCC 8th staging systems. We also made survival comparisons between the 8th and 7th edition system separately for different subgroups.For G1/G2 NF-p-NETs, there were 52 patients classified in AJCC 8th edition stage I, 40 in stage II, 41 in stage III and 19 in stage IV. As for G3 NF-p-NECs, 17, 19, 24, and 18 patients were respectively defined from AJCC 8th edition stage I to stage IV. In terms of the AJCC 7th staging system, the 230 patients with NF-p-NENs were totally distributed from stage I to stage IV (94, 63, 36, 37, respectively). For the survival analysis of both G1/G2 NF-p-NETs and G3 NF-p-NECs, the AJCC 7th edition system failed to discriminate the survival differences when compared stage III with stage II or stage IV (P > .05), while the 8th edition ones could perfectly allocate patients into 4 statistically different groups (P < .05). The HCIs of AJCC 8th stage for G1/G2 NF-p-NETs [HCI=0.658, 95% confidence interval (CI)=0.602-0.741] and stage for G3 NF-p-NECs (HCI=0.704, 95% CI=0.595-0.813) was both statistically larger than those of AJCC 7th stage for different grading NF-p-NENs [(HCI=0.578, 95% CI=0.557-0.649; P=.031), (HCI=0.546, 95% CI=0.531-0.636; P = .019); respectively], indicating a more accurate predictive ability for the survivals of NF-p-NENs.Our data suggested the 2 new AJCC 8th staging systems were superior to its 7th edition for patients with both G1/G2 NF-p-NETs and G3 NF-p-NECs.

Background: Owing to the limited prevalence and heterogeneity, it is difficult to predict long-term survival of non-functional pancreatic neuroendocrine tumours (NF-PNETs).This study aimed to evaluate the factors predicting disease-specific survival (DSS) for well-differentiated NF-PNETs., Methods: Data were collected retrospectively from 256 patients with pancreatic neuroendocrine tumours who underwent surgical resection between January 2009 and December at our institution. Of these, 103 NF-PNETs (40%) were identified for analysis., Results: Of the 103 patients, 54 were male (52%) and the mean age was 52 years (range 21-75 years). Most patients (60/103, 58%) in our series were symptomatic. Seventeen patients (16%) died during follow-up, with a median period of 47 months. There were 88 patients with well-differentiated tumours and 10 of them (10/88, 11%) died of tumour progression. Median DSS after primary resection was 58.8 months (range 16-122 months). Multivariate analysis identified age >52 years (P = 0.038) and tumour grade G2 (P = 0.001) as statistically significant predictors of DSS. There was no association between gender, tumour size, symptoms, surgical procedure, severe complications, tumour location, tumour size, resection margin, positive lymph nodes and vascular invasion with DSS., Conclusion: Tumour grade, age, presence of symptoms and distant metastasis were related to poor DSS of NF-PNETs. Age >52 years and tumour grade G2 might be independent predictors of poor DSS for patients with well-differentiated NF-PNETs., (© 2020 Royal Australasian College of Surgeons.)

Background: Pancreatic neuroendocrine neoplasms (p-NENs) are a group of highly heterogeneous tumors with distinct clinicopathological features and long-term prognosis. In 2017, in order to better stratify patients into prognostic groups and predicting their outcomes, World Health Organization (WHO) officially updated its grading system for p-NENs which distinguished these neoplasms among Grading 1 (G1) pancreatic neuroendocrine tumors (p-NETs), G2 p-NETs, G3 p-NETs and G3 pancreatic neuroendocrine carcinomas (p-NECs). However, this new grading classification for p-NENs has not yet been rigorously validated., Methods: Data of patients who were surgically treated and histopathologically diagnosed as p-NENs at West China Hospital of Sichuan University from January 2002 to December 2018 were retrospectively collected and analyzed according the novel WHO 2017 grading classification., Results: We eventually enrolled 480 eligible patients with p-NENs in our present study, in which 150 patients with WHO 2017 G1 p-NETs, 158 with G2 p-NETs, 64 with G3 p-NETs and 108 with G3 p-NECs were identified. The estimated 5-year overall survival for patients with G1 p-NETs, G2 p-NETs, G3 p-NETs and G3 p-NECs was 75.8, 58.4, 35.1 and 11.1%, with a median survival time of 85.3mons, 67.4mons, 51.3mons and 26.8mons, respectively. Patients with G2 p-NETs present notably worse survival than those with G1 p-NETs (P = 0.03). Survival of G3 p-NETs were significantly worse than that of G1 p-NETs or G2 p-NETs (P < 0.001, P = 0.023, respectively), as well as that when comparing G3 p-NECs with G1 p-NETs or G2 p-NETs (P < 0.001, P < 0.001, respectively). Patients with G3 p-NECs showed statistically shorter survival than those with G3 p-NETs (P < 0.001). Both WHO 2017 and 2010 grading criteria could be independent predictor for the OS of p-NENs (P = 0.016, P = 0.022; respectively). The 95% confidence intervals of WHO 2017 grading classification (0.983-9.454) was slightly smaller than that of WHO 2010 criteria (0.201-13.374), indicating a relatively more accurate predicting ability for the prognosis of p-NENs., Conclusion: The WHO 2017 grading classification for p-NENs could successfully allocate patients into four groups with distinct clinical features and significant survival differences, which might be superior to the WHO 2010 criteria for its better prognostic stratification and more accurate predicting ability.

Method: Data of patients who were surgically treated and clinicopathologically diagnosed as (MH)-NENs secondary to (GEP)-NENs at West China Hospital of Sichuan University from January 2006 to December 2018 were retrospectively collected and analyzed by the grading classification for (GEP)-NENs., Results: We identified 150 patients with (MH)-NENs secondary to (GEP)-NENs, including 10 patients with G1 NETs, 26 with G2 NETs, 33 with G3 NETs, and 81 with G3 NECs. There were significant differences between patients with G1/G2/G3 NETs and those with G3 NECs, such as age at diagnosis ( P =0.041), synchronous liver lesion ( P =0.032), incidental diagnosis ( P =0.014), tumor largest diameter ( P =0.047), vascular invasion ( P =0.017), and extrahepatic metastatic disease ( P =0.029). The estimated 3-year overall survival for patients with G1 NETs, G2 NETs, G3 NETs, and G3 NECs was 100%, 79.4%, 49.5%, and 20.7%, respectively ( P < 0.001). The survival of G1 NETs or G2 NETs was significantly better than that of G3 NETs ( P =0.013, P =0.037, respectively) and G3 NECs ( P =0.001, P < 0.001; respectively). Patients with G3 NECs present notably worse survival than those with G3 NETs ( P =0.012), while survival comparison between G1 NETs and G2 NETs was not statistically different ( P =0.131). The grading classification for (GEP)-NENs was an effective independent predictor of survival for (MH)-NENs secondary to (GEP)-NENs (hazard ratio: 4.234; 95% confidence intervals: 1.984-6.763; P =0.003)., Conclusion: Our demonstration revealed that the grading classification for (GEP)-NENs could well stratify (MH)-NENs secondary to (GEP)-NENs into prognostic groups and supported its wide use in clinical practice., Competing Interests: The authors declare that they have no conflicts of interest and they did not have any sponsorship., (Copyright © 2020 Min Yang et al.)

Objective: To examine copper transporter 1 (CTR1) expression in pancreatic carcinoma cells, orthotopic xenograft pancreatic tumor model and clinical samples, and verify the effect of copper chelating agent ammonium tetrathiomolybdate (TM) regulate the expression of CTR1 in pancreatic carcinoma cells and the inhibition of pancreatic carcinoma., Methods: The expressions of copper transporter CTR1 and antioxidant protein 1 (ATOX1) in 22 clinical pancreatic ductal carcinoma and paracancer tissues 0.5-1 cm away from the tumor were measured by immunohistochemistry (IHC). PANC-1 cells were used to construct 5 orthotopic xenograft pancreatic tumor of nude mice models. Pancreatic cancer tissues and corresponding normal pancreatic tissues were collected, and the expressions of CTR1 and ATOX1 were detected by IHC and compared with clinical tissues. The proliferation of pancreatic carcinoma cells PANC-1 treated with 10, 30, 50, 100 μmol/L TM for 24 h, 48 h, 72 h was measured by CCK8 assay. The migration abilities of PANC-1 cells treated with 50 μmol/L TM for 24 h, 48 h were detected by scratch test. The expressions of CTR1, vascular endothelial growth factor (VEGF) and CyclinD1 proteins in PANC-1 cells treated with 10, 30, 50, 100 μmol/L TM for 48 h were measured by Western blot. Then the subcutaneous tumor-bearing model of nude mice were established with PANC-1 cells, and the growth of tumor was observed after oral administration of 0.3 mg/d and 1.0 mg/d of TM, respectively., Results: The immunohistochemical results indicated that 19 of the 22 clinical pancreatic ductal cancer tissues of carcinoma patients had high expression of CTR1, and the same high expression of CTR1 was found in the orthotopic transplanted tumor tissues of PANC-1 nude mice. The proliferation inhibition of PANC-1 cells increased with the concentration of TM increased and the treatment time prolonged. The expressions of intracellular CTR1, VEGF and CyclinD1 all decreased with the concentration of TM increased. The cell migration ability decreased after the PANC-1 cells treated with TM. The tumor growth of PANC-1 tumor-bearing nude mice was inhibited after different doses of TM were delivered. The reduction in tumor volume and weight was more pronounced in the high-dose TM group ( P <0.05)., Conclusion: The expression of CTR1 is abnormally elevated in pancreatic carcinoma, and treatment with copper chelating agent for this target may help to inhibit pancreatic carcinoma., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Background: Pancreatic neuroendocrine neoplasms (pNENs) that produce hormones leading to symptoms are classified as functional tumors, while others are classified as nonfunctional tumors. The traditional view is that functionality is a factor that affects the prognosis of pNEN patients. However, as the sample sizes of studies have increased, researches in recent years have proposed new viewpoints., Aim: To assess whether functionality is an independent factor for predicting the prognosis of pNEN patients., Methods: From January 2004 to December 2016, data of patients who underwent surgery at the primary site for the treatment of pNENs from the Surveillance, Epidemiology, and End Results (SEER) database and West China Hospital database were retrospectively analyzed., Results: Contemporaneous data from the two databases were analyzed separately as two cohorts and then merged as the third cohort to create a large sample that was suitable for multivariate analysis. From the SEER database, age ( P = 0.006) and T stage ( P < 0.001) were independent risk factors affecting the survival. From the West China Hospital database, independent prognostic factors were age ( P = 0.034), sex ( P = 0.032), and grade ( P = 0.039). The result of the cohort consisting of the combined populations from the two databases showed that race ( P = 0.015), age ( P = 0.002), sex ( P = 0.032) and T stage ( P < 0.001) were independent prognostic factors. In the West China Hospital database and in the total population, nonfunctional pNETs and other functional pNETs tended to have poorer prognoses than insulinoma. However, functionality was not associated with the survival time of patients with pNETs in the multivariate analysis., Conclusion: Functionality is not associated with prognosis. Race, age, sex, and T stage are independent factors for predicting the survival of patients with pNETs., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Although pancreatic neuroendocrine tumors (PNETs) are generally considered to have a favorable overall prognosis after resection, disease recurrence has been observed. Few studies have specifically addressed recurrence after resection of PNETs, especially for non-functioning PNETs (NF-PNETs). The aim of our study is to analyze the recurrence of resected well-differentiated NF-PNETs.Patients who underwent surgical resection for grade 1 and 2 NF-PNETs without synchronous metastasis were identified for analysis. Patients were treated from January 2009 to December 2017 in our institution. Univariate and multivariate cox regression analysis were conducted to identify prognostic factors.Of the 88 patients, 46 were men (52%) and the mean age was 52 years. With a median follow-up of 49.1 months (range, 8-122 months), there were 12 recurrences (14%). Liver was the most common recurrence site (7/12, 58%). The 1-, 3-, and 5-year recurrence-free survival was 99%, 90%, and 88%, respectively. Univariate analysis identified that age >52 years, positive lymph nodes, tumor grade 2, and Ki67 index ≥5% were statistically significant. Multivariate analysis identified that Ki67 index ≥5% (hazard ratio [HR], 4.69; 95% confidence interval [CI], 1.36-16.75, P = .015), positive lymph nodes (HR, 6.75; 95% CI, 1.73-24.43, P = .006) were independently associated with recurrence. The 5-year disease-free survival rate was 53% (95% CI, 14.20-91.81%) for patients with Ki-67 ≥5% or (and) positive lymph nodes, while 95% (95% CI, 82.26-100%) for the patients without these 2 factors.Ki67 index and lymph node status are independently associated with recurrence after resection of well-differentiated NF-PNETs in this study.

Background: In a pathological examination of pancreaticoduodenectomy for pancreatic head adenocarcinoma, a resection margin without cancer cells in 1 mm is recognized as R0; a resection margin with cancer cells in 1 mm is recognized as R1. The preoperative identification of R0 and R1 is of great significance for surgical decision and prognosis. We conducted a preliminary radiomics study based on preoperative CT (computer tomography) images to evaluate a resection margin which was R0 or R1., Methods: We retrospectively analyzed 258 preoperative CT images of 86 patients (34 cases of R0 and 52 cases of R1) who were diagnosed as pancreatic head adenocarcinoma and underwent pancreaticoduodenectomy. The radiomics study consists of five stages: (i) delineate and segment regions of interest (ROIs); (ii) by solving discrete Laplacian equations with Dirichlet boundary conditions, fit the ROIs to rectangular regions; (iii) enhance the textures of the fitted ROIs combining wavelet transform and fractional differential; (iv) extract texture features from the enhanced ROIs combining wavelet transform and statistical analysis methods; and (v) reduce features using principal component analysis (PCA) and classify the resection margins using the support vector machine (SVM), and then investigate the associations between texture features and histopathological characteristics using the Mann-Whitney U -test. To reduce overfitting, the SVM classifier embedded a linear kernel and adopted the leave-one-out cross-validation., Results: It achieved an AUC (area under receiver operating characteristic curve) of 0.8614 and an accuracy of 84.88%. Setting p ≤ 0.01 in the Mann-Whitney U -test, two features of the run-length matrix, which are derived from diagonal sub-bands in wavelet decomposition, showed statistically significant differences between R0 and R1., Conclusions: It indicates that the radiomics study is rewarding for the aided diagnosis of R0 and R1. Texture features can potentially enhance physicians' diagnostic ability., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Bei Hui et al.)

Background: Pancreatic ductal adenocarcinoma (PDA) is one of the most serious causes of death in the world due to its high mortality and inefficacy treatments. MEX3A was first identified in nematodes and was associated with tumor formation and may promote cell proliferation and tumor metastasis. So far, nothing is known about the relationship between MEX3A and PDA., Methods: In this study, the expression level of MEX3A in PDA tissues was measured by immunohistochemistry. The qRT-PCR and western blot were used to identify the constructed MEX3A knockdown cell lines, which was further used to construct mouse xenotransplantation models. Cell proliferation, colony formation, cell apoptosis and migration were detected by MTT, colony formation, flow cytometry and Transwell., Results: This study showed that MEX3A expression is significantly upregulated in PDA and associated with tumor grade. Loss-of-function studies showed that downregulation of MEX3A could inhibit cell growth in vitro and in vivo. Moreover, it was demonstrated that knockdown of MEX3A in PDA cells promotes apoptosis by regulating apoptosis-related factors, and inhibits migration through influencing EMT. At the same time, the regulation of PDA progression by MEX3A involves changes in downstream signaling pathways including Akt, p-Akt, PIK3CA, CDK6 and MAPK9., Conclusions: We proposed that MEX3A is associated with the prognosis and progression of PDA,which can be used as a potential therapeutic target., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background and Objective: We aimed to compare the two new defined tumor-node-metastasis (TNM) systems in the American Joint Committee on Cancer (AJCC) 8th staging manual for overall survival (OS) analysis of G3 pancreatic neuroendocrine carcinomas (p-NECs) that are currently proposed for pancreatic exocrine adenocarcinomas (p-EACs) and G1/G2 pancreatic neuroendocrine tumors (p-NETs), respectively., Methods: The data of patients who were surgically treated and histopathologically diagnosed with G3 p-NECs at West China Hospital of Sichuan University from January 2002 to June 2017 were retrospectively analyzed and compared using the two new AJCC staging systems., Results: Applying the p-EAC AJCC 8th TNM staging system to G3 p-NECs, the estimated 3-year OSs for each stage were 86.7%, 76.0%, 44.5% and 20.7%, respectively (P < 0.001). According to the G1/G2 p-NETs staging system, the estimated OSs at 3 years for each new AJCC stage were 100.0%, 83.6%, 47.1% and 20.7%, respectively (P < 0.001). The system for p-EACs significantly discriminated the survival difference of G3 p-NECs between Stage I and Stage II (P = 0.019), while the other one for G1/G2 p-NETs could not (P = 0.108). The consistent results of Akaike information criteria with Harrell's concordance index indicated that the AJCC 8th staging system for p-EACs was superior when applied to G3 p-NECs for its better prognostic stratification and more accurate prediction ability for OS., Conclusions: Our analysis demonstrated that both TNM systems in the AJCC 8th staging manual were prognostic for patients with G3 p-NECs; however, the classification originally applied to p-EACs was superior and supported its use in clinical practice., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: We aimed to validate the novel American Joint Committee on Cancer (AJCC) eighth edition staging manual for well-differentiated (G1/G2) pancreatic neuroendocrine tumors (pNETs)., Methods: Data of eligible patients were retrospectively collected, grouped, and analyzed by applying the new AJCC system., Results: According to the AJCC eighth staging manual for pNETs, 93, 66, 53, and 42 patients had stage I, II, III, and IV disease, respectively, with estimated 5-year overall survival (OS) rates of 96.9%, 92.8%, 48.4%, and 16.8% (P < 0.005), respectively. A total of 57, 28, 20, and 17 patients with G1 pNETs and 36, 38, 33, and 25 ones with G2 tumors were defined by the new AJCC system as having stage I, II, III, and IV disease, respectively. The estimated 5-year OS for stage I, II, III and IV disease was 100.0%, 97.1%, 52.5%, and 18.2%, respectively, for G1 pNETs (P < 0.005) and 94.2%, 90.3%, 38.7%, and 12.7%, respectively, for G2 tumors (P < 0.005). The novel AJCC classification, tumor grading, and radical resection were all prognostic predictors for OS in patients with pNETs., Conclusions: The new AJCC eighth staging system for well-differentiated pNETs was prognostic and might be adopted in clinical practice.

Background: Enucleation is increasingly used for pancreatic solid pseudopapillary neoplasm (SPN) to preserve function of the pancreas. The data was limited due to rarity of this low-grade neoplasm. We sought to describe the indications, operative technique, short and long-term outcomes after enucleation with largest series of enucleated SPNs., Methods: Data collected retrospectively from 110 patients with SPN who underwent pancreatectomy between 2009 and 2016 in our institution were reviewed. Thirty-one patients underwent enucleation were identified for analysis, and compared with the 70 patients underwent conventional pancreatic resection., Results: Of the 31 patients, 27 (87.1%) were women, and the mean age was 29.8 years (range, 11-49 years). Enucleated SPNs were mostly located in the head/uncinate process of the pancreas (38.7%). Overall morbidity was 25.8%, mainly due to POPF (19.4%), and severe morbidity was only 6.5% with no death. Compared with conventional pancreatic resection, enucleation had a shorter duration of surgery (P < 0.001), less blood loss (P < 0.001), lower rate of exocrine insufficiency (P = 0.033) and comparable morbidity (P = 1), with no increased risk of tumor recurrence (P = 1). The rate of endocrine insufficiency after enucleation seemed lower (Nil vs. 4.5%, P = 0.55)., Conclusions: Enucleation of SPN of the pancreas appears to be feasible and safe for preserving exocrine and endocrine function of the gland. Enucleation with negative surgical margin seems adequate with no increased risk of tumor recurrence. Enucleation could be seriously considered as an alternative to conventional resection for this frequently young population., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Enucleation is increasingly used for benign or low-grade pancreatic neoplasms. Enucleation preserves the pancreatic parenchyma as well as decreases the risk of long-term endocrine and exocrine dysfunction, but may be associated with a higher rate of postoperative pancreatic fistula (POPF). The aim of this study was to assess short-term outcomes, in particular, POPF., Methods: Data were collected retrospectively from all 142 patients who underwent pancreatic enucleation between 2009 and 2014 in our institution were analyzed., Results: Lesions were most frequently located in the head and uncinate process of the pancreas (60.6%), and the most common types were neuroendocrine neoplasms (52.1%). Overall morbidity was 66%, mainly due to POPF (53.5%), and severe morbidity was only 8.4%, including one death (0.7%). Clinical POPF (Grade B or C) occurred in 22 patients (15.5%). Independent risk factors for clinical POPF were age ≥60 years, an episode of acute pancreatitis, and cystic morphology. Tumor size, coverage, histological differentiation, and prolonged operative time were not associated with the risk of POPF., Conclusions: Enucleation is a safe and feasible procedure for benign or low-grade pancreatic neoplasms. The rate of clinical POPF is acceptable, and clinical POPF occurs more frequently in elderly patients (≥60 years of age), patients with cystic neoplasms, or patients with an episode of acute pancreatitis., (© 2017 Wiley Periodicals, Inc.)

Background: There are currently 2 Tumour-Node-Metastasis (TNM) staging systems for pancreatic neuroendocrine tumours (p-NETs) - European Neuroendocrine Tumour Society (ENETS) and American Joint Committee on Cancer (AJCC). P-NETs being heterogeneous, we investigated the prognostic value of the 2 systems in p-NETs, as a whole, and more interestingly in functional and non-functional sub-groups separately, with a view to ascertaining any potential clinical benefits of using one system over the other., Methods: Data from patients with surgically resected p-NETs were retrospectively reviewed. Kaplan-Meier method and Cox Regression proportional hazards model were used to analyse overall survival (OS) and prognostic predictors respectively., Results: In the whole group of 165 patients, both TNM systems successfully discriminated OS differences when comparing stages I and II with stages III and IV ( P <0.05); ENETS stage III patients had a significantly better OS than those in stage IV ( P =0.003). Patients with functional p-NETs in ENETS stage II showed a statistically better OS than those in stages III and IV ( P <0.05). For non-functional tumours, the AJCC staging system could effectively discriminate between the OS differences of patients in stage I with stages III and IV, or stage II with III and IV ( P <0.05). Along with surgical intent and World Health Organisation (WHO) 2010 grade, both ENETS and AJCC staging systems were effective predictors of OS for different function-status p-NETs., Conclusions: The ENETS system might have potential advantages when applied to all p-NETs and to the functional sub-group, while the AJCC system might be clinically more practical for non-functional p-NETs., Competing Interests: CONFLICTS OF INTEREST We declared that there was no competing interests among the authors.

The ability to stratify patients with pancreatic neuroendocrine tumors (p-NETs) into prognostic groups has been hindered by the absence of a commonly accepted staging system. Both the 7th tumor-node-metastasis (TNM) staging guidelines by the American Joint Committee on Cancer (AJCC) and the 2010 grading classifications by the World Health Organization (WHO) were validated to be unsatisfactory.We aim to evaluate the feasibility of combining the latest AJCC and WHO criteria to devise a novel tumor-grading-metastasis (TGM) staging system. We also sought to examine the stage-specific survival rates and the prognostic value of this new TGM system for p-NETs.Data of 120 patients with surgical resection and histopathological diagnosis of p-NETs from January 2004 to February 2014 in our institution were retrospectively collected and analyzed. Based on the AJCC and WHO criteria, we replaced the stage N0 and N1 with stage Ga (NET G1 and NET G2) and Gb (NET G3 and MANEC) respectively, without changes of the definition of T or M stage. The present novel TGM staging system was grouped as follows: stage I was defined as T1-2, Ga, M0; stage II as T3, Ga, M0 or as T1-3, Gb, M0; stage III as T4, Ga-b, M0 and stage IV as any T, M1.The new TGM staging system successfully distributed 55, 42, 12, and 11 eligible patients in stage I to IV, respectively. Differences of survival compared stage I with III and IV for patients with p-NETs were both statistically significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001). Patients in stage I showed better a survival than those in stage II, whereas difference between stages III and IV was not notable (P = 0.001, P = 0.286, respectively). In multivariate models, when the TGM staging system was evaluated in place of the individual T, G, and M variables, this new criteria were proven to be an independent predictor of survival for surgically resected p-NETs (P < 0.05).Stratifying patients well, the current proposed TGM staging system was predictive for overall survival of p-NETs and could be more widely applied in clinical practice.

Objective: To analyze the viability of extended distal pancreatectomy and the associated prognostic factors., Methods: The data of 57 patients with pancreatic adenocarcinoma who underwent standard distal pancreatectomy(DP) or extended distal pancreatectomy(EDP) from January 2011 to December 2014 were reviewed retrospectively. Thirty-five patients were performed with DP and 22 with EDP. Operation safety and survival benefit between DP and EDP were compared by t-test or χ(2) test.Cox regression analysis was used to explore the prognostic indicators., Results: Compared to DP group, operation time((255±91)min vs.(208±80)min)(t=2.066, P=0.044) and ratio of blood transfusion (50.0% vs.17.1%)(χ(2)=12.836, P=0.008) were greater in EDP group, respectively.There were no significant differences in amount of intraoperative blood loss and postoperative duration of hospitalization. Delayed gastric emptying was greater in EDP(22.7% vs.2.9%)(Z=-2.251, P=0.027), while other complications had no differences. Mortality and ratio of relaparotomy also showed no differences. Median survival following DP was 13.1 months compared to 8.2 months following EDP. There was no difference in survival between DP and EDP. According to the results of multivariate analysis, tumor size(RR=1.275, P=0.03)and perioperative blood transfusions(RR=2.673, P=0.04) were independent prognostic factors., Conclusions: Though patients with pancreatic adenocarcinoma who undergo EDP have a worse pathologic staging, they will gain a comparable long-term survival to the patients undergo DP. Tumor size and perioperative blood transfusions are independent prognostic factors.

In 2010, World Health Organization (WHO) reclassified pancreatic neuroendocrine tumors (p-NETs) into 4 main groups: neuroendocrine tumor G1 (NET G1), neuroendocrine tumor G2 (NET G2), neuroendocrine carcinoma G3 (NEC G3), mixed adeno and neuroendocrine carcinoma (MANEC). Clinical value of these newly updated WHO grading criteria has not been rigorously validated. The authors aimed to evaluate the clinical consistency of the new 2010 grading classifications by WHO and the 2010 tumor-node metastasis staging systems by American Joint Committee on Cancer (AJCC) on survivals for patients with surgically resected p-NETs. Moreover, the authors would validate the prognostic value of both criteria for p-NETs.The authors retrospectively collected the clinicopathologic data of 120 eligible patients who were all surgically treated and histopathologically diagnosed as p-NETs from January 2004 to February 2014 in our single institution. The new WHO criteria were assigned to 4 stratified groups with a respective distribution of 62, 35, 17, and 6 patients. Patients with NET G1 or NET G2 obtained a statistically better survival compared with those with NEC G3 or MANEC (P < 0.001). Survivals of NET G1 was also better than those of NET G2 (P = 0.023), whereas difference of survivals between NEC G3 and MANEC present no obvious significance (P = 0.071). The AJCC 2010 staging systems were respectively defined in 61, 36, 12, and 11 patients for each stage. Differences of survivals of stage I with stage III and IV were significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001); whereas comparisons of stage I with stage II and stage III with IV were not statistically significant (P = 0.129, P = 0.286; respectively). Together with radical resection, these 2 systems were both significant in univariate and multivariate analysis (P < 0.05).The newly updated WHO 2010 grading classifications and the AJCC 2010 staging systems could consistently reflect the clinical outcome of patients with surgically resected p-NETs. Meanwhile, both criteria could be independent predictors for survival analysis of p-NETs.

Aim: To investigate the impact of preoperative acute pancreatitis (PAP) on the surgical management of periampullary tumors., Methods: Fifty-eight patients with periampullary tumors and PAP were retrospectively analyzed. Thirty-four patients who underwent pancreaticoduodenectomy (PD) and 4 patients who underwent total pancreatectomy were compared with a control group of 145 patients without PAP during the same period., Results: The preoperative waiting time was significantly shorter for the concomitant PAP patients who underwent a resection (22.4 d vs 54.6 d, P < 0.001) compared to those who did not. The presence of PAP significantly increased the rate of severe complications (Clavien grade 3 or higher) (17.6% vs 4.8%, P = 0.019) and lengthened the hospital stay (19.5 d vs 14.5 d, P = 0.006). A multivariate logistic regression analysis revealed that PAP was an independent risk factor for postoperative pancreatic fistula (OR = 2.91; 95%CI: 1.10-7.68; P = 0.032) and severe complications (OR = 4.70; 95%CI: 1.48-14.96; P = 0.009) after PD. There was no perioperative mortality., Conclusion: PAP significantly increases the incidence of severe complications and lengthens the hospital stay following PD. PD could be safely performed in highly selective patients with PAP.

We aimed to analyze the clinical characteristics and compare the surgical outcome of pancreatic neuroendocrine tumors (p-NETs) using the 2 tumor-node-metastasis (TNM) systems by both the American Joint Committee on Cancer (AJCC) Staging Manual (seventh edition) and the European Neuroendocrine Tumor Society (ENETS). Moreover, we sought to validate the prognostic value of the new AJCC criterion. Data of 145 consecutive patients who were all surgically treated and histologically diagnosed as p-NETs from January 2002 to June 2013 in our single institution were retrospectively collected and analyzed. The 5-year overall survival (OS) rates for AJCC classifications of stages I, II, III, and IV were 79.5%, 63.1%, 15.0%, and NA, respectively, (P < 0.005). As for the ENETS system, the OS rates at 5 years for stages I, II, III, and IV were 75.5%, 72.7%, 29.0%, and NA, respectively, (P < 0.005). Both criteria present no statistically notable difference between stage I and stage II (P > 0.05) but between stage I and stages III and IV (P < 0.05), as well as those between stage II and stages III and IV (P < 0.05). Difference between stage III and IV by ENETS was significant (P = 0.031), whereas that by the AJCC was not (P = 0.144). What's more, the AJCC Staging Manual (seventh edition) was statistically significant in both uni- and multivariate analyses by Cox regression (P < 0.005 and P = 0.025, respectively). Our study indicated that the ENETS TNM staging system might be superior to the AJCC Staging Manual (seventh edition) for the clinical practice of p-NETs. Together with tumor grade and radical resection, the new AJCC system was also validated to be an independent predictor for p-NETs.

Background/aims: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a unique subgroup of tumors in the digestive system but with great clinical heterogeneity. The information on clinical characteristics and prognostic factors of Chinese patients is rather limited., Methodology: We retrospectively analyzed the clinical features, prognostic factors of this disease in a consecutive cohort (N=294) between January 2007 and December 2012., Results: Functioning tumors accounted for 9.2%. Rectum was the most predominant GEP-NETs locations. Abdominal pain occurred in 46.5% patients which was the most common initial symptom. G1, G2 and G3 tumors accounted for 41.5%, 34.7% and 23.8%, respectively. Endoscopy provided the highest detection rate of 95.7%. Consistence between endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNAB) and surgically obtained histological Ki-67 index was 36.4%. Serum CgA test showed a 80.0% consistence with the tissue biopsy. The median follow up duration was 2.8 years (0.02-5.90 years), the median survival was 4.8 years, overall 5-year survival rate was 69.6%. We found colonic localization, tumor size larger than 20 mm, G3 tumor and metastasis were associated with worse outcome (p<0.05)., Conclusion: We found both consistence and differences in GEP-NETs characteristics between our study and previous reports.

Background: Surgical reconstruction following pancreaticoduodenectomy (PD) is associated with significant morbidity and mortality. Because of great variability in definitions of specific complications, it remains unclear whether there is a difference in complication rates following the two commonest types of reconstruction, pancreaticogastrostomy (PG) and pancreaticojejunostomy (PJ). Published consensus definitions for postoperative pancreatic fistula (POPF) have led to a series of randomized clinical trials (RCTs) uniquely placed to address this question., Methods: A literature search was carried out to identify all RCTs comparing postoperative complications of PG versus PJ reconstruction following PD published between January 1995 and December 2013. Pooled odds ratios (ORs) with 95 percent confidence intervals (c.i.) were calculated using fixed-effect or random-effects models., Results: In total, seven RCTs with 1121 patients were included. Four of these trials applied definitions as published by the International Study Group on Pancreatic Fistula (ISGPF). Using ISGPF definitions, the incidence of POPF was lower in patients undergoing PG than in those having PJ (OR 0·50, 95 per cent c.i. 0·34 to 0·73; P < 0·001). Using definitions applied by each individual study, PG was associated with significantly lower rates of POPF (OR 0·51, 0·36 to 0·71; P < 0·001), intra-abdominal fluid collection (OR 0·50, 0·34 to 0·74; P < 0·001) and biliary fistula (OR 0·42, 0·18 to 0·93; P = 0·03) than PJ., Conclusion: Meta-analysis of four RCTs based on ISGPF criteria, and seven RCTs using non-standard criteria, revealed that PG reduced the incidence of POPF after PD compared with PJ., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Background: Pancreatic fistula (PF) is one of the most common complications after pancreaticoduodenectomy (PD). We described a new method of pancreaticojejunostomy (PJ) developed by combining triple-layer duct-to-mucosa PJ with resection of jejunal serosa, which was named as modified layer-to-layer PJ (MLLPJ). The aim of the present study was to observe whether the new technique would effectively reduce the PF rate in comparison with two-layer duct-to-mucosa PJ (TLPJ)., Methods: Data on 184 consecutive patients who underwent the two methods of PJ after standard PD between January 1, 2010 and January 31, 2013 were collected retrospectively from a prospective database. The primary endpoint was the PF rate. The risk factors of PF were investigated by using univariate and multivariate analyses., Results: A total of 88 patients received TLPJ and 96 underwent MLLPJ. Rate of PF for the entire cohort was 8.2%. There were 11 fistulas (12.5%) in the TLPJ group and four fistulas (4.2%) in the MLLPJ group (P = 0.039). Body mass index, pancreatic texture, pancreatic duct diameter, and methods of PJ anastomosis had significant effects on the formation of PF on univariate analysis. Multivariate analysis showed that pancreatic duct diameter ≤3 mm and TLPJ were the significant risk factors of PF., Conclusions: MLLPJ effectively reduces the PF rate after PD in comparison with TLPJ. Results confirm increased PF rates in patients with pancreatic duct diameter ≤3 mm compared with pancreatic duct diameter >3 mm., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: No consensus exists as to whether laparoscopic treatment for pancreatic insulinomas (PIs) is safe and feasible. The aim of this meta-analysis was to assess the feasibility, safety, and potential benefits of laparoscopic approach (LA) for PIs. The abovementioned approach is also compared with open surgery., Methods: A systematic literature search (MEDLINE, EMBASE, Cochrane Library, Science Citation Index, and Ovid journals) was performed to identify relevant articles. Articles that compare the use of LA and open approach to treat PI published on or before April 30, 2013, were included in the meta-analysis. The evaluated end points were operative outcomes, postoperative recovery, and postoperative complications., Results: Seven observational clinical studies that recruited a total of 452 patients were included. The rates of conversion from LA to open surgery ranged from 0%-41.3%. The meta-analysis revealed that LA for PIs is associated with reduced length of hospital stay (weighted mean difference, -5.64; 95% confidence interval [CI], -7.11 to -4.16; P < 0.00001). No significant difference was observed between LA and open surgery in terms of operation time (weighted mean difference, 2.57; 95% CI, -10.91 to 16.05; P = 0.71), postoperative mortality, overall morbidity (odds ratio [OR], 0.64; 95% CI, 0.35-1.17; P = 0.14], incidence of pancreatic fistula (OR, 0.86; 95% CI, 0.51-1.44; P = 0.56), and recurrence of hyperglycemia (OR, 1.81; 95% CI, 0.41-7.95; P = 0.43)., Conclusions: Laparoscopic treatment for PIs is a safe and feasible approach associated with reduction in length of hospital stay and comparable rates of postoperative complications in relation with open surgery., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: To conduct a meta-analysis comparing laparoscopic total gastrectomy (LTG) with open total gastrectomy (OTG) for the treatment of gastric cancer., Methods: Major databases such as Medline (PubMed), Embase, Academic Search Premier (EBSCO), Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library were searched for studies comparing LTG and OTG from January 1994 to May 2013. Evaluated endpoints were operative, postoperative and oncological outcomes. Operative outcomes included operative time and intraoperative blood loss. Postoperative recovery included time to first flatus, time to first oral intake, hospital stay and analgesics use. Postoperative complications comprised morbidity, anastomotic leakage, anastomotic stenosis, ileus, bleeding, abdominal abscess, wound problems and mortality. Oncological outcomes included positive resection margins, number of retrieved lymph nodes, and proximal and distal resection margins. The pooled effect was calculated using either a fixed effects or a random effects model., Results: Fifteen non-randomized comparative studies with 2022 patients were included (LTG - 811, OTG - 1211). Both groups had similar short-term oncological outcomes, analgesic use (WMD -0.09; 95%CI: -2.39-2.20; P = 0.94) and mortality (OR = 0.74; 95%CI: 0.24-2.31; P = 0.61). However, LTG was associated with a lower intraoperative blood loss (WMD -201.19 mL; 95%CI: -296.50--105.87 mL; P < 0.0001) and overall complication rate (OR = 0.73; 95%CI: 0.57-0.92; P = 0.009); fewer wound-related complications (OR = 0.39; 95%CI: 0.21-0.72; P = 0.002); a quicker recovery of gastrointestinal motility with shorter time to first flatus (WMD -0.82; 95%CI: -1.18--0.45; P < 0.0001) and oral intake (WMD -1.30; 95%CI: -1.84--0.75; P < 0.00001); and a shorter hospital stay (WMD -3.55; 95%CI: -5.13--1.96; P < 0.0001), albeit with a longer operation time (WMD 48.25 min; 95%CI: 31.15-65.35; P < 0.00001), as compared with OTG., Conclusion: LTG is safe and effective, and may offer some advantages over OTG in the treatment of gastric cancer.

Background: The safety of pancreaticoduodenectomy has improved significantly. However, alkaline reflux gastritis and marginal ulcer are two substantial problems after pancreaticoduodenectomy., Aims: To identify whether Child reconstruction with a modified Braun enteroenterostomy decreases the incidence of alkaline reflux gastritis and marginal ulcer after pancreaticoduodenectomy better than Roux-en-Y reconstruction., Methods: Data on 57 consecutive patients who underwent standard pancreaticoduodenectomy between January 1, 2008 and January 31, 2012 were collected prospectively. Data on early and late complications of the Child reconstruction with a modified Braun enteroenterostomy and Roux-en-Y were gathered. The risk factors of alkaline reflux gastritis and marginal ulcer were also investigated by using univariate and multivariate analyses., Results: Twenty-five patients received Roux-en-Y and 32 underwent Child reconstruction with a modified Braun enteroenterostomy. Early complications after the two reconstruction methods were insignificant. Significant differences in terms of later postoperative morbidity (P = 0.01) and change in body mass index (P = 0.03) were found 12 months after pancreaticoduodenectomy. No significant difference for alkaline reflux gastritis was observed between the two methods (14.8 vs. 28.6 %, P = 0.24). Marginal ulcer occurred significantly lower in patients with the modified reconstruction than in those with Roux-en-Y reconstruction (11.1 vs. 47.6 %, P = 0.01). Peptic ulcer history, diabetes mellitus, and reconstruction type had a significant effect on marginal ulcer formation., Conclusions: Child reconstruction with a modified Braun enteroenterostomy offers an advantage with respect to marginal ulcer after standard pancreaticoduodenectomy, potentially decreasing the incidence of alkaline reflux gastritis as effectively as Roux-en-Y reconstruction.

Background: Postoperative pancreatic leakage after pancreaticoduodenectomy is often serious. Although some studies have suggested that stenting the anastomosis can reduce the incidence of this complication, the value of stenting in the setting of pancreaticoduodenectomy remains unclear., Methods: Studies comparing outcomes of stent versus no stent, and internal versus external stent placement for pancreaticoduodenectomy were eligible for inclusion. Pooled odds ratios (ORs) with 95 per cent confidence intervals were calculated using fixed- or random-effects models., Results: From a search of the literature published between January 1973 and September 2011, five randomized clinical trials (RCTs) and 11 non-randomized observational clinical studies (OCS) involving 1726 patients were selected for inclusion in this review. Meta-analysis of RCTs revealed that placing a stent in the pancreatic duct did not reduce the incidence of postoperative pancreatic fistula. External stents had no advantage over internal stents in terms of clinical outcome. Subgroup analyses revealed that use of an external stent significantly reduced the incidence of pancreatic fistula (RCTs: OR 0·42, 0·24 to 0·76, P = 0·004; OCS: OR 0·43, 0·27 to 0·68, P < 0·001), delayed gastric emptying (RCTs: OR 0·41, 0·19 to 0·87, P = 0·02) and postoperative morbidity (RCTs: OR 0·55, 0·34 to 0·89, P = 0·02) compared with no stent., Conclusion: Pancreatic duct stenting did not reduce the incidence of pancreatic fistula and other complications in pancreaticoduodenectomy compared with no stenting. Although no difference was found between external and internal stents in terms of efficacy, external stents seemed to reduce the incidence of pancreatic fistula compared with control., (Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Objective: To investigate the expressions of Bcl-2 and Beclin-1 in pancreatic cancer and analyze the correlation between them., Methods: The pancreatic tissue samples were collected from each 6 cases of pancreatic cancer, pancreatic exocrine benign tumor, chronic pancreatitis and normal pancreas and marked as group A, group B, group C and group D, respectively. The mRNA expression levels of Bcl-2 and Beclin-1 were detected by real-time fluorescence quantitative PCR and the protein expression levels of Bcl-2 and Beclin-1 were detected through immunohistochemistry., Results: The expression levels of Bcl-2 mRNA and protein, were the lowest in group D and the highest in group A (P < 0.05). The expression levels of Beclin-1 mRNA and protein in group A were significantly lower than those in group B and group D (P < 0.05). However, the expression levels of Beclin-1 between group A and group C were not significantly different (P > 0.05). The correlation coefficient between Bcl-2 and Beclin-1 protein expression in pancreatic cancer is--0.827 (P = 0. 042)., Conclusion: Compared with normal pancreatic tissue, pancreatic cancer had Bcl-2 expression upregulated and Beclin-1 expression downregulated. The increased anti-apoptotic effect of Bcl-2 and the decreased autophagic effect of Beclin-1 may collaboratively contribute to the occurrence of pancreatic cancer.

Objectives: This study aimed to address whether hydroxyethyl starch (HES) is beneficial for intra-abdominal pressure (IAP) in severe acute pancreatitis (SAP) in early stages., Methods: Forty-one patients with SAP were randomized to HES group (n = 20) and the Ringer's lactate (RL) group (n = 21). The groups received 6% HES 130/0.4 for 8 days and RL solution without colloid, respectively. The primary end point was the IAP. The secondary end points were fluid balance, major organ complications, the Acute Physiology and Chronic Heath Evaluation II score, and the serum levels of C-reactive protein, interleukin-6, and interleukin-8., Results: The characteristics of baseline data were similar in the 2 groups. In the HES group, the IAP was significantly lower in 2 to 7 days, and fewer patients received mechanical ventilation (15.0% vs 47.6%). A negative fluid balance was observed earlier in the HES group than in the RL group (2.5 ± 2.2 vs 4.0 ± 2.5 days)., Conclusions: Fluid resuscitation with HES in the early stages of SAP can decrease the risk of intra-abdominal hypertension and reduce the use of mechanical ventilation.

Objective: To study the role of Th17 cells in the Immune rejection of islet transplantation, explore the feasibility of immune tolerance of islet transplantation induced by the combination applying of IL-23R antibody and Anti-CD154mAb., Methods: The in vitro experiments were divided into 5 groups: Blank control group, SD rat islet cells were cultured alone; A group, co-culture of rat pancreatic islet cells and lymphocytes, without IL-23R antibodies; B, C, D groups, co-culture of rat pancreatic islet cells and lymphocytes, respectively with IL-23R antibodies 0.1 microg/mL, 0.5 microg/mL, 1.0 microg/mL. Cells were harvested for Acridine orange (AO)/propidium iodide (PD) fluorescence staining, insulin and glucagon staining and glucose-stimulated insulin secretion test. The in vivo experiments (the purified islet to be transplanted under the left kidney capsule of the mice) were divided into four groups: Control group, BABL/c mice were transplanted with islets of SD rats with no treatments, IL-23R antibody (200 microg) treatment alone, anti-CD154mAb (200 microg) treatment alone and a combination of both. The blood glucose of the transplanted mice were monitored. The kidney of islet grafts were sliced for HE staining and insulin and glucagon immunohistochemical detection., Results: Three days after mixed cultivation, the glucose stimulation index was 3.66 +/- 0.10 in blank control group, which was higher than that of other groups. Stimulation index of D group was 1.95 +/- 0.75, which was significantly higher than that of other groups. The functional graft survival of all experimental groups were significantly better than that of control group as demonstrated by immunohistochemical staining of insulin and glucagon, as well as in vitro and in vivo experiments. After three days of islet transplantation, the blood glucose of control group was higher than that of experimental groups, but no significant difference was observed among experimental groups., Conclusion: Th17 cells were involved in the islet transplant rejection. The expression of IL-17 could be considerably reduced through the block of the IL-23R, the effect of the block had a positive correlation in a dose-dependent manner. The combination of Anti-CD154 mAb and IL-23R antibody could prevent the acute rejection to some extent. However, there's no significant difference compared with the Anti-CD154mAb alone.

Objective: To assess the value of perforin mRNA and granzyme B mRNA in lymphocytes as an early diagnostic indicator for acute rejection of pancreatic transplantation., Methods: Twenty-four hybrid landraces were divided into three groups (control group, transplantation group, transplantation plus immunosuppressant group) randomly. The landraces in the transplantation group were treated with pancreatoduodenal allotranplantation. The landraces in the transplantation plus immunosuppressant group underwent the same surgery and were intervened simultaneously with CsA, MMF, and Metrisone. Peripheral venous bloods were sampled via subclavic veins one day before the operations and on the 1st, 3rd, 5th and 7th day after the operations. The RNA was extracted from the blood samples. The mRNA of perforin and granzyme B expressed in the lymphocytes were detected by RT-PCR. The serum glucose, insulin and glucagons were also measured with routine methods. The pancreatic graft tissues were collected for pathologic examinations at the 1st, 3rd, 5th and 7th day after the operations., Results: No differences in serum glucose, insulin and glucagons had been detected among the three groups (P>0.05). The landraces in the transplantation plus immunosuppressant group had significantly lower expression of the mRNA of perforin and granzyme B in the lymphocytes and the local transplanted pancreas than those in the transplantation group (P<0.05). The change of mRNA expression of perforin and granzyme B in the lymphocytes occurred 2-4 days earlier than the pathological changes when the acute rejection started., Conclusion: Monitoring the change of mRNA expression of perforin and granzyme B in the lymphocytes from the peripheral blood can help the early diagnosis of acute rejection of pancreatic transplantation.

Objective: To study the early diagnosis value of acute rejection response to perforin and granzyme B protein expressions around transplantation pancreas tissue after pancreatic transplantation., Methods: Twenty-four hybrid landraces were randomly divided into three groups [control group ( I group), transplantation group ( II group), transplantation + immunosuppressive group (III group)]. The transplantation group was treated by pancreatoduodenal allotransplantation, and simultaneously the group of transplantation + immunosuppressants was intervened by cyclosporin A (CsA), mycophenolate mofetil (MMF) and metrisone. The peripheral venous blood was sampled via subclavian vein one day before operation and on the 1st, 3rd, 5th or 7th day after operation respectively, and then the glucose, insulin and glucagons in serum were measured. The grafted pancreatic tissues were collected for pathologic and immunohistochemical examinations at 1st, 3rd, 5th and 7th day after operation., Results: (1) The levels of blood sugar, insulin and glucagons had no significant difference among groups of control, transplantation and transplantation + immunosuppressant group (P>0.05). (2) By comparing with two experimented groups, the expressions of perforin and granzyme B protein in transplantation pancreas tissue had a significant difference between transplantation group and transplantation + immunosuppressive group (P < 0.05). (3) The time of perforin and granzyme B protein expressions in transplantation pancreas tissue after transplantation was 2-4 days earlier than that of pathological changes in acute rejection., Conclusion: The expression alterations of perforin and granzyme B protein are earlier appearance than the pathological changes of acute rejection response in transplantation pancreas tissue, and by combining with routine pathological examination, the acute rejection response can be diagnosed on early stage.