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In this study, aiming at problems that the existing surface roughness prediction models fail to consider the time-varying characteristics of the rough grinding process and the difficulty in feature selection, a real-time surface roughness prediction model based on multi-sensor signal fusion is developed. Firstly, features are extracted from the time domain, frequency domain, and time-frequency domain of force and vibration signal, and then features that do not reflect the time-varying characteristics of the machining process are eliminated. Finally, a multi-sensor signal fusion method is proposed based on the principal component analysis (PCA). Results show that fused features are capable of retaining the physical meaning of original features, and achieving stable and high-precision prediction of surface roughness when they are input into the BP neural network (BPNN). In addition, it is found that the surface roughness at different stages of grinding processing is dominated by different factors. Specifically, during the first stage, the fourth principal component PC4 is the redundant information for the model. However, this feature significantly affects the performance of the model during the second stage. Overall, this paper lays the foundation for understanding mechanisms of time-varying surface roughness in an actual grinding process and realizing accurate monitoring.

Background: The recurrence and liver metastasis rates are still high in pancreatic head cancer with curative surgical resection. A no-touch isolation principle in pancreaticoduodenectomy (PD) may improve this situation, however, the exact advantages and efficacy of these principles have not been confirmed. Materials and methods: Among 370 patients who underwent PD, three centers were selected and classified into two groups: the no-touch PD group (n = 70) and the conventional PD group (n = 300). Propensity score matching was used to control for selection bias at a ratio of 1:1. The confounding variables were age, sex, body mass index, adjuvant chemotherapy, carbohydrate antigen 19-9, tumor size and tumor differentiation. Results: Patients in the no-touch PD group had better overall survival (OS) and disease-free survival (DFS) than those in the conventional PD group (OS: 17 vs. 13 months, p = 0.0035, DFS: 15 vs. 12 months, p = 0.087), with lower 1- and 2-year disease-related mortality rates (1-year: 32.9% vs. 47%, p = 0.032; 2-year: 42.5% vs. 82% p = 0.000) and recurrence and liver metastasis rates (1-year: 30.0% vs. 43.3%, p = 0.041; 2-year: 34.3% vs. 48.7%, p = 0.030). Compared with the matched conventional PD group, the no-touch PD group also had a better OS (17 vs. 12 months, p = 0.032). Conclusions: Our study showed the no-touch isolation principle may be a better choice to improve long-term survival for pancreatic cancer patients.

Postoperative pancreatic fistula (POPF) is a troublesome complication after pancreatic surgeries, and grade C POPF is the most serious situation among pancreatic fistulas. At present, the incidence of grade C POPF varies from less than 1% to greater than 9%, with an extremely high postoperative mortality rate of 25.7%. The patients with grade C POPF finally undergo surgery with a poor prognosis after various failed conservative treatments. Although various surgical and perioperative attempts have been made to reduce the incidence of grade C POPF, the rates of this costly complication have not been significantly diminished. Hearteningly, several related studies have found that intra-abdominal infection from intestinal flora could promote the development of grade C POPF, which would help physicians to better prevent this complication. In this review, we briefly introduced the definition and relevant risk factors for grade C POPF. Moreover, this review discusses the two main pathways, direct intestinal juice spillover and bacterial translocation, by which intestinal microbes enter the abdominal cavity. Based on the abovementioned theory, we summarize the operation techniques and perioperative management of grade C POPF and discuss novel methods and surgical treatments to reverse this dilemma.

In 2017, the World Health Organization (WHO) officially defined pancreatic neuroendocrine neoplasms into well-differentiated tumors, namely G1/G2/G3 pancreatic neuroendocrine tumors, and poorly differentiated carcinomas referring to G3 pancreatic neuroendocrine carcinomas (p-NECs). However, the surgical outcomes and prognostic factors of G3 p-NECs are still unclear. Methods: We retrospectively collected and analyzed the data of eligible patients with G3 p-NECs defined by the WHO 2017 grading classification. Results: We eventually identified 120 patients with G3 p-NECs, including 72 females and 48 males, with a median age of 53 y. The 3-year overall survival (OS) of G3 p-NECs by Kaplan–Meier method was 37.3%. The 3-year OS for functional G3 p-NECs was 57.4%, which was statistically longer than 23.0% of non-functional ones (p = 0.002). Patients with surgical resection presented a significantly better 3-year OS than those with palliative operation (43.3% vs. 13.1%; p < 0.001). The 3-year OS for Stage Ⅰ, Stage Ⅱ, Stage Ⅲ, and Stage Ⅳ was 87.1%, 56.5%, 12.9%, and not applicable, respectively (p < 0.001). We demonstrated in a Cox regression model that palliative operation (p = 0.013), vascular infiltration (p = 0.039), lymph node involvement (p = 0.024), and distant metastasis (p = 0.016) were independent predictors of poor outcome for patients with surgically treated G3 p-NECs. Conclusion: Our data in the present analysis indicated that patients with G3 p-NECs could significantly benefit from surgical resection. Meanwhile, vascular infiltration, lymph node involvement, and distant metastasis were independent predictors of poor outcome for these patients.

Background: Patients after pancreaticoduodenectomy (PD) showed improved glucose tolerance. Evidence for the effect of extrahepatic cholestasis on impaired glucose homeostasis secondary to ductal adenocarcinoma of the pancreatic head is limited. Methods: In this prospective cross-sectional study, 50 patients with ductal adenocarcinoma of the pancreatic head were included to assess the effect of extrahepatic cholestasis on glucose tolerance status based on the oral glucose tolerance test (OGTT) before pancreatic surgery. Results: Patients with extrahepatic cholestasis more frequently suffered from worsened impaired glucose homeostasis (prediabetes and new-onset diabetes, 95.2% vs. 58.6%, p = 0.004). Elevated bile acid level was recognized as an independent risk factor for impaired glucose homeostasis (p = 0.024, OR = 6.85). Hepatic insulin clearance (HIC) was significantly higher in patients with elevated bile acid levels (p = 0.001). A strong positive correlation was found between bile acid levels and HIC (r = 0.45, p = 0.001). Conclusions: This study suggested a connection between elevated bile acid levels and worsened impaired glucose homeostasis through increased insulin clearance function in ductal adenocarcinoma of pancreatic head patients.

The main aim of this study was to investigate the prevalence and prognostic value of preoperative diabetes mellitus (DM) in patients with non-functional pancreatic neuroendocrine neoplasms (NF-PNENs).Data were retrospectively collected from 190 patients with NF-PNENs from January 2009 to December 2019 in a single center.The prevalence of longstanding DM, new-onset DM and impaired fasting glucose (IFG) was 11.6% (22/190), 8.4% (16/190), and 25.8% (49/190), respectively. Regression analysis showed that tumor size, tumor grade and lymph node metastasis were risk factors for new-onset DM and IFG. Multivariate survival analysis demonstrated preoperative new-onset DM (hazard ratio [HR], 4.33; P = 0.009) and IFG (HR, 4.53; P = 0.027) as independent predictors of poor recurrence-free survival (RFS) in patients with NF-PNENs.Preoperative new-onset DM and IFG are associated with aggressive tumor behavior and poor RFS in patients with NF-PNENs.

Background and Purpose. Neuroendocrine neoplasms occurring in the liver are very rare, in which metastatic hepatic neuroendocrine neoplasms [(MH)-NENs] secondary to gastroenteropancreatic NENs [(GEP)-NENs] account for their majority. The clinical features and long-term survival of (MH)-NENs secondary to (GEP)-NENs were not clear, especially for each grading group of G1 neuroendocrine tumors (NETs), G2 NETs, and G3 NETs and G3 neuroendocrine carcinomas (G3 NECs). 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.

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 P = 0.023, respectively), as well as that when comparing G3 p-NECs with G1 p-NETs or G2 p-NETs (P P P 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.

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.

Objectives Transforming growth factor β (TGF-β) signaling pathway is one of the core pathways in pancreatic ductal adenocarcinoma (PDAC). Prognostic value of TGF-β pathway genes as a functionally related group in PDAC is rarely studied. Methods Seventy-two PDAC patients who underwent surgery between November 30, 2015, and September 13, 2017, in West China Hospital, Sichuan University, were identified and included in this study. Whole-exome sequencing or targeted next-generation sequencing was performed with tumor tissue. Clinicopathologic characteristics and survival data were retrospectively collected and analyzed. Results Genetic alterations were detected in 71 patients (98.6%). Although 1 patient (1.4%) had one genetic alteration, 33 patients (45.8%) had 2 to 4 alterations and 37 patients (51.4%) had 5 or more alterations. Twenty-five patients with TGF-β pathway alteration were identified as TGF-βm+ group. Other 47 patients were TGF-βm- group. Mutation of TGF-β pathway was independently associated with inferior survival (hazard ratio, 2.22, 95% confidence interval, 1.05-4.70, P = 0.04), especially in patients accepting radical surgery (hazard ratio, 3.25, 95% confidence interval, 1.01-10.49, P = 0.04). Conclusions Inferior prognosis was observed in PDACs with mutations of TGF-β pathway. Genomic information could help screen out patients at risk after surgery, and adjuvant therapy might benefit this subgroup of PDACs.

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.

Background: There is a high prevalence of diabetes mellitus (DM) in patients with pancreatic ductal adenocarcinoma (PDAC). An inflammatory response is considered as a potential mechanism involved in the process. The systemic immune-inflammation (SII) index is an integrated and novel inflammatory indicator developed in recent years. The purpose of this study was to determine the relationship between the SII and DM secondary to PDAC. Method: Patients with a confirmed diagnosis of PDAC were analyzed in this cross-sectional study. Anthropometric measures, glucose-related data (including fasting glucose, 2 h OGTT, glycated hemoglobin, fasting insulin, and fasting c-peptide), tumor characteristics (tumor volumes, location and stages), and the periphery blood inflammatory index (white blood cell count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and SII) were recorded. The inflammation index was analyzed for its association with glucose-related parameters. Multivariable logistic regression analysis was used to analyze the association between SII levels and DM secondary to PDAC. Results: Blood cell results showed that the white blood cell count, neutrophils, lymphocytes, monocytes, platelets, the neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were higher in patients with diabetes. It was worth noting that SII significantly increased in patients with diabetes secondary to PDAC (4.41 vs. 3.19, p < 0.0001). Multivariable logistic regression analysis showed that SII (OR: 2.024, 95%CI: 1.297, 3.157, p = 0.002) and age (OR: 1.043, 95%CI: 1.01, 1.077, p = 0.011) were the risk factors for DM secondary to PDAC after adjusting for covariates. According to Spearmen correlation analysis, SII was positively correlated with fasting glucose (r = 0.345, p < 0.0001), 2 h OGTT (r = 0.383, p < 0.0001), HbA1c (r = 0.211, p = 0.005), fasting insulin (r = 0.435, p < 0.0001), fasting C-peptide (r = 0.420, p < 0.0001), and HOMA2-IR (r = 0.491, p < 0.0001). Conclusions: In conclusion, SII is significantly increased among patients with DM secondary to PDAC and is associated with the DM in patients with PDAC (OR: 2.382, 95% CI: 1.157, 4.903, p = 0.019). Additionally, SII is significantly correlated with insulin resistance. We are the first to investigate the relationship between SII and diabetes secondary to PDAC and further confirm the role of an inflammatory response in this process. More studies need to be designed to clarify how inflammatory responses participate.

The no-touch isolation technique has been widely used in cancer surgery as a strategy to prevent cancer cells from spreading; however, it is difficult to apply in laparoscopic pancreaticoduodenectomy (LPD). Here, we describe an orthotopic resection surgical technique that applies a no-touch principle for LPD and can help with the in situ resection of tumors. In implementing this surgical strategy, Kocher’s maneuver was not performed first. Instead, after the exploration of the abdominal cavity, the distal stomach and the pancreatic neck were transected. Then, the dissection of the uncinate process of the pancreas, the duodenum, and the superior mesenteric vein and artery is carried out via an inferior infracolic approach. Finally, the pancreatic head and duodenum were removed in situ. Among the 41 patients who underwent this technique, two (4.9%) required conversion to open surgery due to uncontrolled bleeding. The average operative time was 335 min (248–1055 min). The mean estimated blood loss was 300 mL (50–1250 mL). Two patients (4.9%) underwent combined PV resection and reconstruction; six patients (14.6%) required a blood transfusion; two patients (4.9%) suffered from postoperative bleeding; two patients (4.9%) suffered from Grade B pancreatic fistulas; one patient (2.4%) suffered from bile leakage; and three patients (7.3%) suffered from abdominal fluid collection. No patients died during the perioperative period. Therefore, orthotopic LPD using an inferior infracolic approach is safe and feasible for patients with malignant pancreatic head and periampullary tumors. However, further investigations are required to elucidate its oncological benefits.

Background The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic ductal adenocarcinoma (PDAC) excludes extrapancreatic extension from the assessment of T stage and restages tumors with mesenterico-portal vein (MPV) invasion into T1-3 diseases according to tumor size. However, MPV invasion is believed to be correlated with a poor prognosis. Aim To analyze whether the inclusion of MPV invasion can further improve the 8th edition of the AJCC staging system for PDAC. Methods This study retrospectively included 8th edition AJCC T1-3N0-2M0 patients undergoing pancreaticoduodenectomy/total pancreatectomy from two cohorts and analyzed survival outcomes. In the first cohort, a total of 7539 patients in the surveillance, epidemiology, and end results database was included, and in the second cohort, 689 patients from the West China Hospital database were enrolled. Results Cox regression analysis showed that MPV invasion is an independent prognostic factor in both databases. In the MPV- group, all pairwise comparisons between the survival functions of patients with different stages were significant except for the comparison between patients with stage IIA and those with stage IIB. However, in the MPV+ group, pairwise comparisons between the survival functions of patients with stage IA, stage IB, stage IIA, stage IIB, and stage III were not significant. T1-3N0 patients in the MPV+ group were compared with the T1N0, T2N0, and T3N0 subgroups of the MPV- group; only the survival of MPV-T3N0 and MPV+T1-3N0 patients had no significant difference. Further comparisons of patients with stage IIA and subgroups of stage IIB showed (1) no significant difference between the survival of T2N1 and T3N0 patients; (2) a longer survival of T1N1 patients that was shorter than the survival of T2N0 patients; and (3) and a shorter survival of T3N1 patients that was similar to that of T1-3N2 patients. Conclusion The modified 8th edition of the AJCC staging system for PDAC proposed in this study, which includes the factor of MPV invasion, provides improvements in predicting prognosis, especially in MPV+ patients.

Neoadjuvant therapy for pancreatic neuroendocrine tumors may potentially aid downstaging, increase the possibility of radical surgery. We herein report a case of a 63-year-old man who had been diagnosed with locally advanced small-cell neuroendocrine carcinomas of the pancreas according to the diagnostic biopsy. The patient received 6 courses of etoposide and cisplatin as neoadjuvant therapy in an attempt to stop tumor progression, which promoted obvious tumor shrinkage without adverse effects and allowed subsequent Appleby procedure, the distal pancreatectomy with celiac artery resection. The patient showed no recurrence in the follow-up of a contrast-enhanced computed tomographic scan, which is 8 months after surgery. To the best of our knowledge, this is a rare case to report etoposide and cisplatin administration before surgery for unresectable pancreatic neuroendocrine carcinoma promoted a pathological partial response and finally achieved a radical surgery, providing a novel therapeutic option for patients with locally advanced pancreatic neuroendocrine carcinoma.

Duodenal gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal tract. For localized or potentially resectable GISTs, surgery is the first choice. But the important and complex anatomical structure adjacent to the duodenum makes surgical management for duodenal GISTs challenging and few comprehensive surgical strategies have been described. This study aims to provide new comprehensive surgical strategies for duodenal GISTs by summarizing the surgical approaches and outcomes of duodenal GISTs in different locations in our center in the past 11 years.Information from patients who underwent surgical resection for duodenal GISTs at our facility during the past 11 years was retrospectively analyzed.Ninety-two patients have received surgical procedures in the facility. Twenty-three, 31, 3, and 35 patients underwent wedge resection, segmental resection, pancreatic head-preserving duodenectomy, and pancreaticoduodenectomy, respectively. The mean operative times were 212.6 (150-270), 260 (180-370), 323 (300-350), and 354.9 (290-490) min; the mean blood loss was 226.1 (100-400), 303.2 (100-600), 500 (400-600), and 582.9 (200-1300) ml, respectively. R0 margins were obtained in 21, 29, 3, and 32 patients, respectively.For duodenal GISTs without invasion of the ampulla of Vater or the pancreatic head, a limited resection (such as wedge resection, segmental resection, or pancreatic head-preserving duodenectomy) is feasible. For duodenal GISTs with an invasion of the ampulla of Vater or the pancreatic head, a pancreaticoduodenectomy is still necessary.

Background In pancreatic cancer, acute pancreatitis (AP) is a serious morbidity, but its negative effect on long-term outcomes remains to be elucidated. Aim To investigate the effects of AP on the tumor recurrence pattern of pancreatic ductal adenocarcinoma (PDAC) and tumor-specific survival. Methods The medical records of 219 patients with curative pancreatectomy for pancreatic cancer at the Pancreatic Surgery Center of West China Hospital from July 2012 to December 2016 were analyzed retrospectively. The severity of acute pancreatitis was classified according to the Atlanta classification of AP. The patient demographics and tumor characteristics were assessed. Early recurrence was defined as a relapse within 12 mo after surgery. Overall and disease-free survival and recurrence patterns were analyzed. Mild acute pancreatitis was excluded because its negative effects can be negligible. Results Early recurrence in AP group was significantly higher than in non-AP group (71.4% vs 41.2%; P = 0.009). Multivariate analysis of postoperative early recurrence showed that moderate or severe AP was an independent risk factor for an early recurrence [odds ratio (OR): 4.13; 95% confidence interval (CI): 1.41-12.10; P = 0.01]. The median time to recurrence was shorter in patients with AP than in those without (8.4 vs 12.8 mo; P = 0.003). Multivariate analysis identified AP as an independent prognostic factor for overall survival [relative risk (RR): 2.35; 95%CI: 1.45-3.83] and disease-free survival (RR: 2.24; 95%CI: 1.31-3.85) in patients with PDAC. Conclusion Patients with moderate or severe acute pancreatitis developed recurrences earlier than those without. Moderate or severe AP is associated with shorter overall and disease-free survival of patients with PDAC.

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.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies with in vivo study shows that monensin blunts PDAC xenograft tumor growth by suppressing cell proliferation via targeting EGFR pathway. Therefore, our findings demonstrate that monensin can be repurposed as an effective anti-pancreatic cancer drug even though more investigations are needed to validate its safety and anticancer efficacy in pre-clinical and clinical models.

Immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 (PD-1) and its ligand PD-L1 and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibodies, are involved in T cell-mediated immune response augmentation and promote anti-tumor immunity. Cancer patients treated with combination of immunotherapy, chemotherapy, radiotherapy, and targeted therapy exhibit superior clinical outcomes and tolerance compared with patients treated with monotherapies. However, immutherapy is associated with several concomitant immune-related adverse events (irAEs). For instance, IrAEs interferes with function of gastrointestinal tract, endocrine, dermatological, nervous system and musculoskeletal systems. ICIs-associated pancreatic injury might causes decrease in endocrine and exocrine pancreatic function, resulting in metabolic and nutritional disorders. Clinicians who administer immune checkpoint inhibitors to cancer patients are diagnosed with hyperglycemia, abdominal pain and steatorrhea. Currently, the precise mechanism of ICIs-associated pancreatic injury has not been fully explored. This paper summarizes incidence, diagnosis, clinical characteristics, potential mechanisms, and treatment management patterns of ICIs-associated pancreatic AEs based on previous studies. In addition, possible management approaches of these adverse effects are presented in this paper. in the findings summarized in this paper lay a basis for management of ICIs-associated pancreatic AEs and expanding future immunotherapy applications.

Acute pancreatitis is an inflammatory disorder of the pancreas associated with substantial morbidity and mortality, which is characterized by a rapid depletion of glutathione (GSH). Cysthionine-β-synthase (CBS) is a key coenzyme in GSH synthesis, and its deficiency is related to a variety of clinical diseases. However, whether CBS is involved in the pathogenesis of acute pancreatitis remains unclear. First, we found that CBS was downregulated in both in vivo and in vitro AP models. The pancreatic damage and acinar cell necrosis related to CBS deficiency were significantly improved by VB 12, which stimulated clearance of reactive oxygen species (ROS) by conserving GSH. Furthermore, EX-527 (a specific inhibitor of SIRT1) exposure counteracted the protective effect of VB 12 by promoting oxidative stress and aggravating mitochondrial damage without influencing CBS, indicating that vitamin B12 regulates SIRT1 to improve pancreatical damage by activating CBS. In conclusion, we found that VB 12 protected acute pancreatitis associated with oxidative stress via CBS/SIRT1 pathway.

Gastric adenosquamous carcinoma (gasc) is a rare entity with distinctive characteristics that are not fully understood. In the present study, we evaluated the characteristics of this rare disease. The U.S. Surveillance, Epidemiology, and End Results program database was searched to determine the clinicopathologic features, prognostic factors, and treatments for 246 patients with gasc and 42,735 patients with gastric adenocarcinoma (gac). Relative to gac, gasc is associated with higher proportions of cardia involvement, high-grade tumours, deep tumour invasion, metastatic lymph nodes, and chemotherapy treatment. In patients who underwent potentially curative surgery (pcs), gasc was associated with a higher proportion of radiotherapy use and poorer overall survival (p < 0.001), although no significant difference (p = 0.802) was observed after propensity score matching (psm). Multivariate analysis after psm revealed that the independent prognostic factors for gasc were TNM stage [hazard ratio (hr): 1.512, p = 0.021] and regional nodes examined (hr: 0.588, p = 0.02). In patients with advanced disease, no significant difference in survival between gasc and gac was observed (p = 0.212), although survival was significantly poorer for gasc after psm (p = 0.019). Multivariate analysis after psm revealed that the independent prognostic factors for gasc were invasion depth (hr: 1.303, p = 0.036) and chemotherapy (hr: 0.444, p < 0.001). Relative to gac, gasc was associated with more aggressive features, although survival outcomes were similar after pcs. Chemotherapy remains a mainstay of treatment for patients with advanced gasc, but its role remains unclear for patients who are undergoing pcs.

Background: Not only to assess the prognostic influence on standardization circumferential resection margin R0 and R1 Status but also to research the prognostic influence on adjuvant chemotherapy to PV/SMV, SMA resection margins﹤1mm. The SMV and SMA resection margins had an important prognostic influence to PDAC patients, and the survival prognosis of R1 status(resection margin﹤1mm) was poor. Methods: A total of 228 patients performed PD between 2015 and 2019 were included, which was assessment of standardization circumferential resection margin status and survival prognosis. There were cancer cells within 1mm clearance of PV/SMV and SMA resection margins named R1 PV/SMV, SMA, and no cancer cells named R0 PV/SMV, SMA.Results: The resection margin 1mm clearance of PV/SMV, SMA (P=0.010) and postoperative adjuvant chemotherapy (P=0.001) were prognostic independent predictors. The median survival time was 22 months of 166 R0 PV/SMV, SMA patients (73%) compared to 15 months of 62 R1 PV/SMV, SMA patients (27%) (P=0.005). There was the statistical significance of survival time between the adjuvant chemotherapy group and the none-adjuvant chemotherapy group (P=0.000). In the R1 PV/SMV, SMA group, there was no statistical significance of survival time between the adjuvant chemotherapy patients and the none-adjuvant chemotherapy patients (P=0.208).Conclusions: Patients undergoing PD for PDAC, postoperative adjuvant chemotherapy could not improve the poor survival prognosis of R1 PV/SMV, SMA resection patients. The resection margins of PV/SMV, SMA had a greater prognostic influence on survival than postoperative adjuvant chemotherapy.Trial registration: Clinicaltrials.gov/ct2/show/NCT02928081

BackgroundRadical pancreaticoduodenectomy is the only possible cure for pancreatic head adenocarcinoma, and although several RCT studies have suggested the extent of lymph node dissection, this issue remains controversial. This article wanted to evaluate the survival benefit of different lymph node dissection extent for radical surgical treatment of pancreatic head adenocarcinoma.MethodsA total of 240 patients were enrolled in the study, 212 of whom were randomly divided into standard lymphadenectomy group (SG) or extended lymphadenectomy group (EG), there were 97 patients in SG and 95 patients in EG receiving the radical pancreaticoduodenectomy.ResultThe demography, histopathology and clinical characteristics were similar between the two groups. The 2-year overall survival rate in the SG was higher than the EG (39.5% vs 25.3%; p=0.034). The 2-year overall survival rate in the SG who received postoperative adjuvant chemotherapy was higher than the EG (60.7% vs 37.1%; p=0.021). There was no significant difference in the overall incidence of complications between the two groups (p=0.502). The number of peripheral blood lymphocytes of the EG was significantly lower than that in the SG at 1 week (mean [SD], 0.957[0.429] vs 1.278[0.521], p=0.001) and 1 month (mean [SD], 1.538[0.618] vs 1.917[0.796], p=.009) after operation.ConclusionIn multimodality therapy system, the efficacy of chemotherapy should be based on the appropriate lymphadenectomy extent, and the standard extent of lymphadenectomy is optimal for resectable pancreatic head adenocarcinoma. The postoperative slowing of peripheral blood lymphocyte recovery might be one of the reasons why extended lymphadenectomy did not result in survival benefits.Clinical trial registrationThis trial was registered at ClinicalTrials.gov (NCT02928081) in October 7, 2016. https://clinicaltrials.gov/

Background: To identify preoperative computed tomography radiomics texture features which correlate with resection margin status and prognosis in resected pancreatic head adenocarcinoma. Methods: Improved prognostication methods utilizing novel non-invasive radiomic techniques may accurately predict resection margin status preoperatively. In an ongoing concerning pancreatic head adenocarcinoma, the venous enhanced CT images of 86 patients who underwent pancreaticoduodenectomy were selected, and the resection margin (>1 mm or ≤1 mm) was identified by pathological examination. Three regions of interests (ROIs) were then taken from superior to inferior facing the superior mesenteric vein and artery. Subsequent Laplacian-Dirichlet based texture analysis methods extracting algorithm flows of texture features within ROIs were analyzed and assessed in relation to patient prognosis.Results: Patients with >1 mm resection margin had an overall improved survival compared to ≤1 mm (P < 0.05). Distance 1 and 2 of Gray level co-occurrence matrix, high Gray-level run emphasis of run-length matrix and average filter of wavelet transform (all P < 0.05) were correlated with resection margin status (Area under the curve was 0.784, sensitivity was 75% and specificity was 79%). The energy of wavelet transform, the measure of smoothness of histogram and the variance in 2 direction of Gabor transform are independent predictors of overall survival prognosis, independent of resection margin.Conclusions: Resection margin status (>1 mm vs ≤1 mm) is a key prognostic factor in pancreatic adenocarcinoma and CT radiomic analysis have the potential to predict resection margin status preoperatively, and the radiomic labels may improve selection neoadjucant therapy. Trial registration: Clinicaltrials.gov/ct2/show/NCT02928081.