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With advancements in genomics and immunology, immunotherapy has emerged as a revolutionary strategy for tumor treatment. However, pancreatic ductal adenocarcinoma (PDAC), an immunologically "cold" tumor, exhibits limited responsiveness to immunotherapy. This study aimed to address the urgent need to uncover PDAC's immune microenvironment heterogeneity and identify the molecular mechanisms driving immune evasion. Using single-cell RNA sequencing datasets and spatial proteomics, we discovered LIM domain only 7 (LMO7) in PDAC cells as a previously unrecognized driver of immune evasion through Treg cell enrichment. LMO7 was positively correlated with infiltrating regulatory T cells (Tregs) and dysfunctional CD8+ T cells. A series of in vitro and in vivo experiments demonstrated LMO7's significant role in promoting Treg cell differentiation and chemotaxis while inhibiting CD8+ T cells and natural killer cell cytotoxicity. Mechanistically, LMO7, through its LIM domain, directly bound and promoted the ubiquitination and degradation of Foxp1. Foxp1 negatively regulated transforming growth factor-beta (TGF-ß) and C-C motif chemokine ligand 5 (CCL5) expression by binding to sites 2 and I/III, respectively. Elevated TGF-ß and CCL5 levels contribute to Treg cell enrichment, inducing immune evasion in PDAC. Combined treatment with TGF-ß/CCL5 antibodies, along with LMO7 inhibition, effectively reversed immune evasion in PDAC, activated the immune response, and prolonged mouse survival. Therefore, this study identified LMO7 as a novel facilitator in driving immune evasion by promoting Treg cell enrichment and inhibiting cytotoxic effector functions. Targeting the LMO7-Foxp1-TGF-ß/CCL5 axis holds promise as a therapeutic strategy for PDAC. Graphical abstract revealing LMO7 as a novel facilitator in driving immune evasion by promoting Tregs differentiation and chemotaxis, inducing CD8+ T/natural killer cells inhibition.
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OBJECTIVES: To investigate the value of extracellular volume (ECV) fraction and fat fraction (FF) derived from dual- energy CT (DECT) for predicting postpancreatectomy acute pancreatitis (PPAP) after pancreatoduodenectomy (PD). METHODS: This retrospective study included patients who underwent DECT and PD between April 2022 and September 2022. PPAP was determined according to the International Study Group for Pancreatic Surgery (ISGPS) definition. Iodine concentration (IC) and FF of the pancreatic parenchyma were measured on preoperative DECT. The ECV fraction was calculated from iodine map images of the equilibrium phase. The independent predictors for PPAP were assessed by univariate and multivariable logistic regression analysis and receiver operating characteristic (ROC) curve analysis. RESULTS: Sixty-nine patients were retrospectively enrolled (median age, 60 years; interquartile range, 55-70 years; 47 men). Of these, nine patients (13.0%) developed PPAP. These patients had lower portal venous phase IC, equilibrium phase IC, FF, and ECV fraction, and higher pancreatic parenchymal-to-portal venous phase IC ratio and pancreatic parenchymal-to-equilibrium phase IC ratio, compared with patients without PPAP. After multivariable analysis, ECV fraction was independently associated with PPAP (odd ratio [OR], 0.87; 95% confidence interval [CI]: 0.79, 0.96; p < 0.001), with an area under the curve (AUC) of 0.839 (sensitivity 100.0%, specificity 58.3%). CONCLUSIONS: A lower ECV fraction is independently associated with the occurrence of PPAP after PD. ECV fraction may serve as a potential predictor for PPAP after PD. CLINICAL RELEVANCE STATEMENT: DECT-derived ECV fraction of pancreatic parenchyma is a promising biomarker for surgeons to preoperatively identify patients with higher risk for postpancreatectomy acute pancreatitis after PD and offer selective perioperative management. KEY POINTS: PPAP is a complication of pancreatic surgery, early identification of higher-risk patients allows for risk mitigation. Lower DECT-derived ECV fraction was independently associated with the occurrence of PPAP after PD. DECT aids in preoperative PAPP risk stratification, allowing for appropriate treatment to minimize complications.
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The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of cancer-associated fibroblasts (CAFs) as part of the host response to tumor cells. The origins and functions of transcriptionally diverse CAF populations in PDAC remain poorly understood. Tumor cell-intrinsic genetic mutations and epigenetic dysregulation may reshape the TME; however, their impacts on CAF heterogeneity remain elusive. SETD2, a histone H3K36 trimethyl-transferase, functions as a tumor suppressor. Through single-cell RNA sequencing, we identify a lipid-laden CAF subpopulation marked by ABCA8a in Setd2-deficient pancreatic tumors. Our findings reveal that tumor-intrinsic SETD2 loss unleashes BMP2 signaling via ectopic gain of H3K27Ac, leading to CAFs differentiation toward lipid-rich phenotype. Lipid-laden CAFs then enhance tumor progression by providing lipids for mitochondrial oxidative phosphorylation via ABCA8a transporter. Together, our study links CAF heterogeneity to epigenetic dysregulation in tumor cells, highlighting a previously unappreciated metabolic interaction between CAFs and pancreatic tumor cells.
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Fibroblastos Asociados al Cáncer , Carcinoma Ductal Pancreático , Epigénesis Genética , Neoplasias Pancreáticas , Microambiente Tumoral , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Ratones , Animales , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismoRESUMEN
BACKGROUND: Marginal ulcer (MU) is one of the postoperative complications of pancreaticoduodenectomy (PD), which needs particular attention in postoperative treatments. METHODS: The data of 190 patients who underwent PD and follow-up gastroscopic review due to upper GI symptoms within two years were retrospectively analyzed. The incidence of MU and risk factors were analyzed based on personal history, surgical procedure, past medical history, postoperative complications, and other relevant indicators. RESULTS: The proportion of MU in patients who underwent endoscopic follow-up for upper gastrointestinal symptoms in the postoperative period in this cohort was 10.5% (20/190). Advanced age (69y vs. 59y, P â= â0.012), alcohol consumption (20% vs. 8.2%, P â= â0.03), and cigarette smoking (35% vs. 14.7%, P â= â0.022) were associated with an increased incidence of MU. Longer surgery time (276.5min vs. 240min, P â= â0.049), postoperative bleeding (10% vs. 1.8%, P â= â0.030), and failure to take antacid regularly postoperatively (75% vs. 97.1%, P â= â0.000) would increase the risk of MU; taking antacid regularly was an independent protective factor for postoperative anastomotic ulceration (OR: 0.091, CI: 0.022-0.383, P â= â0.001). CONCLUSION: Advanced age, alcohol consumption, smoking, longer operation time, or postoperative extraluminal hemorrhage are associated with MU. Regular use of antacids is an independent protective factor against the development of MU.
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Pancreaticoduodenectomía , Complicaciones Posoperatorias , Humanos , Masculino , Pancreaticoduodenectomía/efectos adversos , Femenino , Persona de Mediana Edad , Factores de Riesgo , Incidencia , Anciano , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Adulto , Úlcera Péptica/epidemiología , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Úlcera Gástrica/epidemiología , Úlcera Gástrica/etiologíaRESUMEN
BACKGROUND: Pyroptosis, as a type of inflammatory programmed cell death, has been studied in inflammatory diseases and numerous cancers but its role in pancreatic ductal adenocarcinoma (PDAC) remains further exploration. METHODS: A TCGA-PDAC cohort was enrolled for bioinformatics analysis to investigate the effect of pyroptosis on the prognosis and drug sensitivity of patients. PA-TU-8988T and CFPAC-1 cells were selected for investigating the role of GSDMC in PDAC. RESULTS: A distinct classification pattern of PDAC mediated by 21 pyroptosis-related genes (PRGs) was identified. It was suggested that higher pyroptosis activity was associated with poor prognosis of patients and higher tumor proliferation rates. We further established a prognostic model based on three PRGs (GSDMC, CASP4 and NLRP1) and the TCGA-PDAC cohort was classified into low and high-risk subgroups. It is noteworthy that the high-risk group showed significantly higher tumor proliferation rates and was proved to be highly correlated with oxaliplatin resistance. Further experiments suggested that overexpression of GSDMC promoted the proliferation and oxaliplatin resistance of PA-TU-8988T cells in vitro and vivo, while downregulation of GSDMC showed opposite effects in CFPAC-1 cells. Finally, we found that the activation of pentose phosphate pathway (PPP) was the mechanism by which GSDMC overexpression promoted the proliferation and oxaliplatin resistance of pancreatic cancer cells. CONCLUSIONS: In this study, we found that higher pyroptosis activity is associated with worse prognosis and oxaliplatin resistance of PDAC patients. In addition, as a core effector of pyroptosis, GSDMC promoted proliferation and oxaliplatin resistance of pancreatic cancer cells, which will provide new therapeutic target for PDAC patients.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Piroptosis/genética , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Gasderminas , Biomarcadores de Tumor/metabolismoRESUMEN
The Forming Limit Stress Diagram (FLSD) can accurately describe the forming process of high-strength steel. However, obtaining FLSD is relatively difficult. In order to predict fracture in advanced high-strength dual-phase (DP) steels, limit maximum and limit minimum principal strains of sheet were obtained through multiple sets of test and simulation. Two material parameters, strength coefficient K and hardening exponent n are introduced into the FLSD function which is established by the strain-stress transformation function. The function shows that the k-value determines the value of the maximum principal stress, while the n-value affects the curvature of the curve. Verification of correctness by testing and simulation to within 10% accuracy. This paper explores a new approach to FLSD research based on material properties, which can expand the application scope of FLSD.
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BACKGROUND: For infected necrotizing pancreatitis (INP), percutaneous catheter drainage (PCD) is now widely acknowledged as the initial intervention in a step-up approach, followed, if necessary, by minimally invasive necrosectomy or even open pancreatic necrosectomy. However, an overemphasis on PCD may cause a patient's condition to deteriorate, leading to missed surgical opportunities or even death. This study aimed to develop a simple and convenient scoring tool for assessing the need for surgery in INP patients who received PCD procedures. METHODS: In an observational study conducted between April 2015 and December 2020, PCD was utilized as the initial step to treat 143 consecutive INP patients. A surgical necrosectomy was performed when the patient failed to respond. Risk factors of PCD failure (i.e., need for surgical necrosectomy) were identified by multivariate logistic regression models. An integer-based risk scoring tool was developed using the ß coefficients derived from the logistic regression model. RESULTS: In 62 (43.4%) patients, PCD was successful, while the remaining 81 (56.6%) individuals required subsequent surgical necrosectomy. In the multivariate model, organ failure, percentage of pancreatic necrosis, extrapancreatic necrosis volume, and mean CT density of extrapancreatic necrosis volume were associated with a need for surgical necrosectomy. A predictive scoring tool based on these four factors demonstrated an area under the receiver operating characteristic curve (AUC) of 0.893. Under the scoring tool, a total score of 4 or more indicates a high possibility of surgical necrosectomy being required (at least 80%). Using the coordinates of the receiver operating characteristic curve (ROC), the sensitivity and specificity at this threshold are 0.802 and 0.903, respectively. CONCLUSIONS: A risk score model integrating organ failure, percentage of pancreatic necrosis, extrapancreatic necrosis volume, and mean CT density of extrapancreatic necrosis volume can identify INP patients at high risk for necrosectomy. The straightforward risk assessment tool assists clinicians in stratifying INP patients and making more judicious medical decisions.
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Pancreatitis Aguda Necrotizante , Humanos , Pancreatitis Aguda Necrotizante/complicaciones , Pancreatitis Aguda Necrotizante/diagnóstico por imagen , Pancreatitis Aguda Necrotizante/cirugía , Resultado del Tratamiento , Drenaje/métodos , Factores de Riesgo , Necrosis/cirugía , Estudios RetrospectivosRESUMEN
Background: Diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to the lack of specific symptoms and screening methods. Only less than 10% of PDAC patients are candidates for surgery at the time of diagnosis. Thus, there is a great global unmet need for valuable biomarkers that could improve the opportunity to detect PDAC at the resectable stage. This study aimed to develop a potential biomarker model for the detection of resectable PDAC by tissue and serum metabolomics. Methods: Ultra-high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS) was performed for metabolome quantification in 98 serum samples (49 PDAC patients and 49 healthy controls (HCs)) and 20 pairs of matched pancreatic cancer tissues (PCTs) and adjacent noncancerous tissues (ANTs) from PDAC patients. Univariate and multivariate analyses were used to profile the differential metabolites between PDAC and HC. Results: A total of 12 differential metabolites were present in both serum and tissue samples of PDAC. Among them, a total of eight differential metabolites showed the same expressional levels, including four upregulated and four downregulated metabolites. Finally, a panel of three metabolites including 16-hydroxypalmitic acid, phenylalanine, and norleucine was constructed by logistic regression analysis. Notably, the panel was capable of distinguishing resectable PDAC from HC with an AUC value of 0.942. Additionally, a multimarker model based on the 3-metabolites-based panel and CA19-9 showed a better performance than the metabolites panel or CA19-9 alone (AUC: 0.968 vs. 0.942, 0.850). Conclusions: Taken together, the resectable early-stage PDAC has unique metabolic features in serum and tissue samples. The defined panel of three metabolites has the potential value for early screening of PDAC at the resectable stage.
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BACKGROUND: Delayed gastric emptying (DGE) is a common complication after pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PPPD). However, its risk factors are still unclear. This meta-analysis aimed to identify the potential risk factors of DGE among patients undergoing PD or PPPD. MATERIALS AND METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library, Google Scholar, and ClinicalTrial.gov for studies that examined the clinical risk factors of DGE after PD or PPPD from inception through 31 July 2022. We pooled odds ratios (ORs) with 95% CIs using random-effects or fixed-effects models. We also performed heterogeneity, sensitivity, and publication bias analyses. RESULTS: The study included a total of 31 research studies, which involved 9205 patients. The pooled analysis indicated that out of 16 nonsurgical-related risk factors, three risk factors were found to be associated with an increased incidence of DGE. These risk factors were older age (OR 1.37, P =0.005), preoperative biliary drainage (OR 1.34, P =0.006), and soft pancreas texture (OR 1.23, P =0.04). On the other hand, patients with dilated pancreatic duct (OR 0.59, P =0.005) had a decreased risk of DGE. Among 12 operation-related risk factors, more blood loss (OR 1.33, P =0.01), postoperative pancreatic fistula (POPF) (OR 2.09, P <0.001), intra-abdominal collection (OR 3.58, P =0.001), and intra-abdominal abscess (OR 3.06, P <0.0001) were more likely to cause DGE. However, our data also revealed 20 factors did not support stimulative factors influencing DGE. CONCLUSION: Age, preoperative biliary drainage, pancreas texture, pancreatic duct size, blood loss, POPF, intra-abdominal collection, and intra-abdominal abscess are significantly associated with DGE. This meta-analysis may have utility in guiding clinical practice for improvements in screening patients with a high risk of DGE and selecting appropriate treatment measures.
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Absceso Abdominal , Gastroparesia , Humanos , Pancreaticoduodenectomía/efectos adversos , Gastroparesia/epidemiología , Gastroparesia/etiología , Píloro/cirugía , Fístula Pancreática/etiología , Factores de Riesgo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Absceso Abdominal/epidemiología , Absceso Abdominal/etiología , Vaciamiento GástricoRESUMEN
RATIONALE AND OBJECTIVE: To identify the radiological features and clinical biomarkers that could predict the occult metastasis (OM) of pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: This retrospective study included PDAC patients who were radiologically diagnosed resectable (R) or borderline resectable (BR) and underwent surgical exploration from January 2018 to December 2021. Depending on whether distant metastases were found during the exploration, patients were divided into OM and non-OM groups. Univariate and multivariable logistic regression analyses were performed to determine the radiological and clinical predictive factors for occult metastasis. Model performance was determined by discrimination and calibration. RESULTS: A total of 502 patients (median age, 64 years; interquartile range, 57-70 years; 294 men) were enrolled, among which 68 (13.5%) patients were found with distant metastases, with 45 liver-only, 19 peritoneal-only, four patients had both liver and peritoneal metastases. Rim enhancement and peripancreatic fat stranding were more frequent in the OM group than in the non-OM group. Tumor size (p = 0.028), tumor resectability (p = 0.031), rim enhancement (p < 0.001), peripancreatic fat stranding (p < 0.001) and level of CA125 (p = 0.021) were independent predictors of occult metastasis according to the multivariable analyses, and the areas under the curve (AUCs) of these characteristics were 0.703, 0.594, 0.638, 0.655, 0.631, respectively. The combined model showed the highest AUC of 0.823. CONCLUSIONS: Rim enhancement, peripancreatic fat stranding, tumor size, tumor resectability and level of CA125 are risk factors for OM of PDAC. The combined model of radiological and clinical features may help the preoperative prediction of OM in PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Masculino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Tomografía Computarizada por Rayos X , Neoplasias PancreáticasRESUMEN
Obesity has been linked to a higher risk of pancreatic cancer. However, the mechanism by which obesity promote pancreatic carcinogenesis is still unclear. We investigated the effect of obesity on pancreatic carcinogenesis in Pdx1-Cre; LSL-KrasG12D+/- (KC) mice. Metformin was administrated to rescue the effects of obesity and NETs. The pro-tumorigenic effects of neutrophil extracellular traps (NETs) were further evaluated in vivo and vitro. We found that obesity significantly promoted the progression of murine pancreatic ductal intraepithelial neoplasia (mPanIN). The proliferation rate and epithelial-mesenchymal transition (EMT) of mPanIN ductal cells were increased in obese mice. More visceral adipocytes, PD-L1+ neutrophil infiltration and NETs formation were found in the pancreas of obese mice and visceral adipocytes could recruit neutrophils and promote NETs formation. The latter could induce an inflammatory response in ductal cells via TLR4-dependent pathways both in vivo and vitro, as demonstrated by upregulation of IL-1ß. Metformin and DNase I significantly reversed the pro-tumorigenic effects of obesity and NETs in vivo and in vitro. Our study provides causal evidence for the contribution of obesity in promoting pancreatic carcinogenesis in genetic model and reveals the mechanism by NETs to regulate mPanIN progression.
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Carcinoma in Situ , Carcinoma Ductal Pancreático , Trampas Extracelulares , Metformina , Neoplasias Pancreáticas , Lesiones Precancerosas , Ratones , Animales , Ratones Obesos , Metformina/farmacología , Carcinoma Ductal Pancreático/genética , Trampas Extracelulares/metabolismo , Páncreas/metabolismo , Neoplasias Pancreáticas/genética , Carcinogénesis , Obesidad/complicacionesRESUMEN
BACKGROUND/OBJECTIVES: To evaluate perioperative safety and outcome of parenchyma-preserving pancreatectomy and risk factors of metastasis and recurrence for patients with solid pseudopapillary neoplasm (SPN). METHODS: Demographic data, operative and pathological parameter, follow-up data of patients with SPN undergoing their first operation were collected in our single center from May 2016 to October 2021 and compared between regular pancreatectomy group and parenchyma-preserving surgery group. Risk factors for metastasis and recurrence were investigated. RESULTS: A total of 194 patients were included, 154 of whom were female and the average age of all patients was 33 years old. Most patients were asymptomatic, with the most common complaint being abdominal pain or discomfort. Of them, 62 patients underwent parenchyma-preserving pancreatectomy including middle segment pancreatectomy and enucleation, and 132 patients underwent regular pancreatectomy including pancreaticoduodenectomy, distal pancreatectomy and total pancreatectomy. Patients in the parenchyma-preserving surgery group had a shorter duration of operation, less intraoperative bleeding, and decreased risk of combined organ removal and blood transfusion, with no statistical significance yet. The two groups exhibited a similar incidence of postoperative complications including grade B and C pancreatic fistula, delayed gastric emptying, postoperative pancreatic hemorrhage, and other complications, as well as radiological intervention, relaparotomy and the length of postoperative hospital stay. There were no perioperative deaths. All the patients, except 18 of those who discontinued follow-up, were alive with a median follow-up time of 31 months. Three patients in the regular pancreatectomy group were observed to have liver metastasis, and no metastasis was observed in the parenchyma-preserving surgery group. Significant risk factors for tumor metastasis and recurrence were tumor size, angioinvasion, and nerve infiltration. CONCLUSIONS: Parenchyma-preserving surgery did not significantly increase the frequency of perioperative complications or recurrence and might be preferable if comprehensive conditions allow.
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Neoplasias Pancreáticas , Humanos , Femenino , Adulto , Masculino , Neoplasias Pancreáticas/patología , Pronóstico , Pancreatectomía/efectos adversos , Pancreaticoduodenectomía , Hemorragia Posoperatoria/etiología , Estudios Retrospectivos , Páncreas/cirugía , Páncreas/patología , Resultado del TratamientoRESUMEN
Background: The artery involvement explains the majority of primary unresectability of non-metastatic pancreatic cancer patients and both arterial resection and artery-sparing dissection techniques are utilized in curative-intent pancreatectomies for artery-involving pancreatic cancer (ai-PC) patients. Methods: This narrative review summarized the history of resectability evaluation for ai-PC and attempted to interpret its current pitfalls that led to the divergence of resectability prediction and surgical exploration, with a focus on the rationale and the surgical outcomes of the sub-adventitial divestment technique. Results: The circumferential involvement of artery by tumor currently defined the resectability of ai-PC but insufficient to preclude laparotomy with curative intent. The reasons behind could be: 1. The radiographic involvement of tumor to arterial circumference was not necessarily resulted in histopathological artery wall invasion; 2. the developed surgical techniques facilitated radical resection, better perioperative safety as well as oncological benefit. The feasibility of periadventitial dissection, sub-adventitial divestment and other artery-sparing techniques for ai-PC depended on the tumor invasion depth to the artery, i.e., whether the external elastic lamina (EEL) was invaded demonstrating a hallmark plane for sub-adventitial dissections. These techniques were reported to be complicated with preferable surgical outcomes comparing to arterial resection combined pancreatectomies, while the arterial resection combined pancreatectomies were considered performed in patients with more advanced disease. Conclusions: Adequate preoperative imaging modalities with which to evaluate the tumor invasion depth to the artery are to be developed. Survival benefits after these techniques remain to be proven, with more and higher-level clinical evidence needed. Key message: The current resectability evaluation criteria, which were based on radiographic circumferential involvement of the artery by tumor, was insufficient to preclude curative-intent pancreatectomies for artery-involving pancreatic cancer patients. With oncological benefit to be further proven, periarterial dissection and arterial resection have different but overlapping indications, and predicting the tumor invasion depth in major arteries was critical for surgical planning.
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BACKGROUD: Pancreatic cancer (PC) is a highly invasive malignancy with extremely poor prognosis. STK31 has been identified as a cancer-testis (CT) gene, but its function in PC has not been elucidated well. METHODS: The effect of STK31 on cell proliferation, migration and invasion was investigated by in vitro and in vivo experiments and total RNA sequencing and targeted bisulfite sequencing was applied to explore the potential regulatory mechanisms of STK31 in PC. RESULTS: By analysis of tissue samples and the clinicopathologic features, we found that STK31 was reactivated in PC and associated with poor prognosis. In addition, the vitro and vivo studies indicated that STK31 could promote PC progression by facilitating cell proliferation, migration and invasion, and the indication. Targeted Bisulfite Sequencing showed that STK31 was regulated by methylation. Furthermore, the results of total RNA sequencing suggested that STK31 was closely related to signal transduction, metabolism, and the immune system. CONCLUSIONS: This study demonstrates that STK31, as a CT gene, can promote the development of PC and is regulated by methylation. STK31 could be considered as a potential therapeutic target for PC.
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Neoplasias Pancreáticas , Testículo , Masculino , Humanos , Testículo/metabolismo , Metilación , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proliferación Celular , Línea Celular Tumoral , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias PancreáticasRESUMEN
BACKGROUND: Early detection of pancreatic ductal adenocarcinoma (PDAC) may improve the prognosis of patients. This study was to identify metabolic features of PDAC and to discover early detection biomarkers for PDAC by tissue and serum metabolomics analysis. METHODS: We conducted nontargeted metabolomics analysis in tissue samples of 51 PDAC tumors, 40 noncancerous pancreatic tissues (NT), and 14 benign pancreatic neoplasms (BP) as well as serum samples from 80 patients with PDAC, 36 with BP, and 48 healthy controls (Ctr). The candidate metabolites identified from the initial analysis were further quantified using targeted analysis in serum samples of an independent cohort of 22 early stage PDAC, 27 BP, and 27 Ctr subjects. Unconditional binary logistic regression analysis was used to construct the optimal model for PDAC diagnosis. RESULTS: Upregulated levels of fatty acids and lipids and downregulated amino acids were observed in tissue and serum samples of PDAC patients. Proline, creatine, and palmitic acid were identified as a panel of potential biomarkers to distinguish PDAC from BP and Ctr (odds ratio = 2.17, [95% confidence interval 1.34-3.53]). The three markers showed area under the receiver-operating characteristic curves (AUCs) of 0.854 and 0.865, respectively, for the comparison of PDAC versus Ctr and PDAC versus BP. The AUCs were 0.830 and 0.852 in the validation set and were improved to 0.949 and 0.909 when serum carbohydrate antigen 19-9 (CA19-9) was added to the model. CONCLUSION: The novel metabolite biomarker panel identified in this study exhibited promising performance in distinguishing PDAC from BP or Ctr, especially in combination with CA19-9.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Antígeno CA-19-9 , Biomarcadores de Tumor , Estudios de Casos y Controles , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/metabolismo , Metabolómica , Neoplasias PancreáticasRESUMEN
PURPOSE: This study aims to study the depth of artery wall tumour invasion in patients undergoing surgery for pancreatic ductal adenocarcinoma. METHODS: Specimens from 47 pancreatic cancer patients with major arterial (splenic, SA; celiac, CA; common hepatic, CHA) invasion were examined: 45 left (distal) pancreatectomies, including 11 celiac artery resections, and two total pancreatectomies. Dissection of tumour-invaded arteries in 25 fresh specimens was attempted ex vivo using the sub-adventitial dissection technique (SDT). Tumour invasion of 66 arteries was graded using the tumour-free distance (TFD) from the external elastic lamina (EEL): 0 = no arterial invasion; I = TFD ≥ 1 mm; II = TFD < 1 mm; and grade III = EEL invasion. RESULTS: AJCC TNM staging was IA = 1 (2%), IB = 4 (9%), IIA = 5 (11%), IIB = 17(36%) and III = 20 (43%). Grade III tumour invasion was found in 17/47(36%) SAs, in 5/11 (45%) CAs and in 1/8 (13%) CHAs (p = 0.318). Attempted ex vivo SDT undertaken in 33 arteries from 25 specimens was complete in 16 and incomplete in 17 arteries. The median (IQR) TFD was 0.97 (0.11-2.54) mm in dissected and 0.14 (0.10, 0.14) mm in non-dissected SAs (p = 0.034). EEL tumour invasion occurred in 0/12 (0%) dissected compared to 7/13 (54%) non-dissected SAs (p = 0.005). Grades 0, I, II and III invasion were found in four (33%), two (17%) and six (50%), respectively, of 12 dissected SAs and grades II and III in six 6 (46%) and seven (54%), respectively, of 13 non-dissected SAs (p = 0.002). CONCLUSIONS: The grading system described may form the basis for classification to further develop arterial dissection techniques for pancreatic cancer.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Pancreatectomía/métodos , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Arteria Celíaca/cirugía , Neoplasias PancreáticasRESUMEN
Malignant pancreatic tumors have early metastasis, aggressive behavior and poor prognosis. Surgeons often need to judge whether a patient needs prompt surgery when a pancreatic lesion is found. The accessory spleen is a congenital developmental malformation rather than a tumor and does not require surgical resection. Here, we report a 47-year-old man who underwent routine gastroscopic examination, and a submucosal eminence of the duodenal bulb was detected. The patient was asymptomatic and laboratory tests were unremarkable. Duodenal neuroendocrine neoplasm (G2) was considered following endoscopic submucosal dissection (ESD). Further examination showed a lesion in the tail of the pancreas and multiple accessory spleens. The lesion in the tail of the pancreas was Ga-68 positive and was highly considered a pancreatic neuroendocrine tumor (pNET). Based on this clinical evidence, laparoscopic spleen-preserving distal pancreatectomy (Kimura) was performed. However, the results of the postoperative pathological diagnosis indicated an intrapancreatic accessory spleen (IPAS). Given the findings of this case, we should explore more accurate diagnostic methods for IPAS to avoid unnecessary surgery.
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BACKGROUND: Pancreatojejunostomy stricture (PJS) is a rare long-term complication of pancreaticojejunal anastomosis. This study aimed to investigate the role of surgery in the management of pancreatojejunostomy strictures. METHODS: The database of the Pancreas Center of Nanjing Medical University was retrospectively screened for patients who underwent a surgical revision for PJS between June 2012 and August 2019, and their clinical characteristics and management modalities were reviewed. RESULTS: Fourteen consecutive cases were retrieved, the median age at index operation was 41.1 years (19-71). The average time between the two operations was 70.6 months (8-270 months). Index procedures included pancreaticoduodenectomy (PD) (7/14, 50%), pylorus-preserving PD (4/14, 28.6%), Berger procedure (2/14, 14.3%), and middle pancreatectomy (1/14, 7.1%). The diameter of the main pancreatic duct was < 4 mm in all 14 cases, and nine underwent pancreaticojejunostomy (PJ) stenting during the index operation. The most frequent complaints were abdominal pain (6/14, 42.9%), recurrent acute pancreatitis (6/14, 42.9%), pancreatic fistula (1/14, 7.1%), and abdominal distention (1/14, 7.1%). The diagnosis of PJ stricture was confirmed by computed tomography or magnetic resonance imaging in all cases. All patients had a main duct diameter > 5 mm before surgical revision. All patients underwent wedge excision with interrupted one-layer suturing with absorbable sutures and without stent placement. In this series, only one patient required reoperation. Upon follow-up, 11 of 12 patients had complete resolution of the PJ stricture. CONCLUSION: PJS is a long-term complication of pancreatojejunostomy. Surgical revision of the anastomosis is a safe and effective treatment modality.
Asunto(s)
Pancreatoyeyunostomía , Pancreatitis , Enfermedad Aguda , Anastomosis Quirúrgica/efectos adversos , Constricción Patológica/complicaciones , Constricción Patológica/cirugía , Humanos , Fístula Pancreática , Pancreaticoduodenectomía/efectos adversos , Pancreaticoduodenectomía/métodos , Pancreatoyeyunostomía/efectos adversos , Pancreatoyeyunostomía/métodos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Reoperación/efectos adversos , Estudios RetrospectivosRESUMEN
Pancreatic cancer (PC) is a highly malignant solid tumor with insidious onset and easy early metastasis. Despite tremendous efforts devoted to research in this field, the mechanisms underlying PC tumorigenesis and progression remain unclear. Additionally, robust biomarkers and satisfactory therapeutic strategies for clinical use in PC patients are still lacking. Circular RNAs (circRNAs) are a new type of non-coding RNA originating from precursor messenger RNAs, with a covalent continuous closed-loop structure, strong stability and high specificity. Accumulating evidence suggests that circRNAs may participate in PC development and progression. Abnormal expression of circRNAs in PC is considered a vital factor that affects tumor cell proliferation, migration, invasion, apoptosis, angiogenesis and drug resistance. In this review of relevant articles published in recent years, we describe the basic knowledge concerning circRNAs, including their classification, biogenesis, functions and research approaches. Moreover, the biological roles and clinical significance of circRNAs related to PC are discussed. Finally, we note the questions remaining from recent studies and anticipate that further investigations will address these gaps in knowledge in this field. In conclusion, we expect to provide insights into circRNAs as potential targets for specific PC diagnosis and treatment in the future.