Application of ultrasound shear wave elastography in pre-operative and quantitative prediction of clinically relevant post-operative pancreatic fistula after pancreatectomy: a prospective study for the investigation of risk evaluation model.

OBJECTIVES: The aim of this study was to modify recognized clinically relevant post-operative pancreatic fistula (CR-POPF) risk evaluation models with quantitative ultrasound shear wave elastography (SWE) values and identified clinical parameters to improve the objectivity and reliability of the prediction. METHODS: Two prospective, successive cohorts were initially designed for the establishment of CR-POPF risk evaluation model and the internal validation. Patients who scheduled to receive pancreatectomy were enrolled. Virtual touch tissue imaging and quantification (VTIQ)-SWE was used to quantify pancreatic stiffness. CR-POPF was diagnosed according to 2016 International Study Group of Pancreatic Fistula standard. Recognized peri-operative risk factors of CR-POPF were analyzed, and the independent variables selected from multivariate logistic regression were used to build the prediction model. RESULTS: Finally, the CR-POPF risk evaluation model was built in a group of 143 patients (cohort 1). CR-POPF occurred in 52/143 (36%) patients. Constructed from SWE values and other identified clinical parameters, the model achieved an area under the receiver operating characteristic curve of 0.866, with sensitivity, specificity, and likelihood ratio of 71.2%, 80.2%, and 3.597 in predicting CR-POPF. Decision curve of modified model revealed a better clinical benefit compared to the previous clinical prediction models. The models were then examined via internal validation in a separate collection of 72 patients (cohort 2). CONCLUSIONS: Risk evaluation model based on SWE and clinical parameters is a potential non-invasive way to pre-operatively, objectively predict CR-POPF after pancreatectomy. CLINICAL RELEVANCE STATEMENT: Our modified model based on ultrasound shear wave elastography may provide an easy access in pre-operative and quantitative evaluating the risk of CR-POPF following pancreatectomy and improve the objectivity and reliability of the prediction compared to previous clinical models. KEY POINTS: • Modified prediction model based on ultrasound shear wave elastography (SWE) provides an easy access for clinicians to pre-operatively, objectively evaluate the risk of clinically relevant post-operative pancreatic fistula (CR-POPF) following pancreatectomy. • Prospective study with validation showed that the modified model provides better diagnostic efficacy and clinical benefits compared to previous clinical models in predicting CR-POPF. • Peri-operative management of CR-POPF high-risk patients becomes more possible.

Prediction of pancreatic fistula after pancreatectomy by virtual touch tissue imaging and quantification (VTIQ) technology.

OBJECTIVES: The aim of this study was to quantitatively evaluate the stiffness of pancreatic parenchyma and solid focal pancreatic lesions (FPLs) by virtual touch tissue imaging and quantification (VTIQ) technique and to investigate the potential usefulness of VTIQ method in the prediction of post-operative pancreatic fistula (POPF) after pancreatectomy. METHODS: In this prospective study, patients who scheduled to undergo pancreatectomy were initially enrolled and received VTIQ assessment within one week before surgery. VTIQ elastography (Siemens ACUSON Sequoia, 5C-1 transducer) was used to measure the shear wave velocity (SWV) value of FPLs and the body part pancreatic parenchyma. The palpation stiffness of pancreas was qualitatively evaluated during operation by surgeons. POPF was finally diagnosed and graded through a three-weeks post-operative follow-up according to international study group of pancreatic fistula (ISGPF). SWV values were compared between POPF positive and negative group. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficacy of SWV value in predicting POPF. RESULTS: From December 2020 to June 2021, 44 patients were finally enrolled in this study, among which, 26 patients were identified to develop POPF after pancreatectomy. The SWV value of pancreatic parenchyma in POPF positive group was significantly lower than that in POPF negative group (P = 0.001). However, there was no significant difference in palpation stiffness between the two groups (P = 0.124). Besides, neither the SWV value of FPL nor the SWV ratio between FPL to surrounding pancreatic parenchyma differ significantly between POPF positive and negative group (P > 0.05). Taking SWV value of pancreatic parenchyma >1.10 m/s as a cut-off value for predicting POPF, area under the receiver operating characteristic curve (AUROC) was 0.864 with 72.2% sensitivity, 92.3% specificity, 86.7% positive predictive value (PPV) and 82.8% negative predictive value (NPV), respectively. CONCLUSIONS: VTIQ technique might be a potential non-invasive imaging method to predict POPF before pancreatectomy in future clinical practice.

Risk factors affecting prognosis in metachronous liver metastases from WHO classification G1 and G2 gastroenteropancreatic neuroendocrine tumors after initial R0 surgical resection.

BACKGROUND: Here we describe the treatments and prognosis for metachronous metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) after initial R0 surgical resection at a large center in China. METHODS: The clinicopathological data and survival outcomes for 108 patients (median age, 54.0 years) with metachronous hepatic metastatic GEP-NETs disease who were initially treated using R0 surgical resection between August 2003 and July 2014 were analyzed using one-way comparisons, survival analysis, and a predictive nomogram. RESULTS: Fifty-five (50.9%) patients had pancreatic NETs and 92 (85.2%) had G2 primary tumors. For treatment of the hepatic metastases, 48 (44.4%) patients received liver-directed local treatment (metastasectomy, radiofrequency ablation, transcatheter arterial chemoembolization, etc.), 15 (13.9%) received systemic treatment (interferon, somatostatin analogs, etc.), and 45 (41.7%) received both treatments. Multivariable analyses revealed that OS was associated with hepatic tumor number (P < 0.001), treatment modality (P = 0.045), and elevated Ki-67 index between the metastatic and primary lesions (P = 0.027). The predictive nomogram C-index was 0.63. CONCLUSIONS: A higher Ki-67 index in metastases compared to primary tumor was an independent factor for poor prognosis. Local treatment was associated with prolonged survival of hepatic metastatic GEP-NET patients. Optimal treatment strategies based on clinicopathological characteristics should be developed.

Difference analysis in prevalence of incidental pancreatic cystic lesions between computed tomography and magnetic resonance imaging.

BACKGROUND: The purpose was to investigate the difference of detection rate of incidental pancreatic cystic lesions (PCLs) with computed tomography (CT) and magnetic resonance imaging (MRI) and to compare the difference between CT and MRI and to explore the effect of this difference on surgical resection. METHODS: We reviewed the diagnostic reports for incidental PCLs between 2013 and 2016. Images of PCLs would be re-evaluated. Clinical and imaging data were recorded. The chi-square and independent t-test were conducted for categorical and continuous variables. RESULTS: The prevalence of PCLs was 1.91% (1038/54210) and 3.36% (1282/38099) on CT and MRI respectively, and increased with increasing age (P < 0.001). No significant differences were found in the annual prevalence of PCLs on CT (P = 0.796) and MRI (P = 0.213) from 2013 to 2016 while the number of examinations was increasing every year. The annual detection rate of MRI for small PCLs (< 20 mm) was significantly higher than CT (P < 0.001), but was not significantly different for large PCLs (≥20 mm). The rate of surgical resection of PCLs (≥20 mm) in MRI group was higher than CT (55.2% vs. 37.0%, P < 0.001). CONCLUSIONS: The detection rate of PCLs on CT and MRI tended to be stable despite increasing scan volumes. Female had a slightly more frequency of PCLs than male. MRI detected more small PCLs(< 20 mm) and had higher impact on surgical resection of large PCL(≥20 mm) compared with CT.

Preoperative ultrasound radiomics for predicting clinically relevant postoperative pancreatic fistula after pancreatectomy.

OBJECTIVES: To evaluate the efficacy of the radiomics model based on preoperative B-mode ultrasound (BMUS) and shear wave elastography (SWE) for predicting the occurrence of clinically relevant-postoperative pancreatic fistula (CR-POPF). METHODS: Patients who were scheduled to undergo pancreatectomy were prospectively enrolled and received ultrasound assessment within one week before surgery. The risk factors of POPF (grades B and grades C) were analyzed. Preoperative BMUS images, SWE values of pancreatic lesions and surrounding parenchyma were used to build preoperative prediction radiomics models. Radiomic signatures were extracted and constructed using a minimal Redundancy Maximal Relevance (mRMR) algorithm and an L1 penalized logistic regression. A combined model was built using multivariate regression which incorporated radiomics signatures and clinical data. RESULTS: From January 2020 to November 2021, a total of 147 patients (85 distal pancreatectomies and 62 pancreaticoduodenectomies) were enrolled. During the three-week follow-up after pancreatectomy, the incidence rates of grade B/C POPF were 28.6% (42/147). Radiomic signatures constructed from BMUS of pancreas parenchymal regions (panRS) achieved an area under the receiver operating characteristic curve (AUC) of 0.75, accuracy of 68.7%, sensitivity of 85.7 %, and specificity of 61.9 % in preoperative noninvasive prediction of CR-POPF. The AUC of the radiomics model increased to 0.81 when panRS was used for the prediction of CR-POPF after pancreaticoduodenectomy. CONCLUSIONS: Radiomics model based on ultrasound images was potentially useful for predicting CR-POPF. Patients with high-risk factors should be closely monitored when postoperation.

Contrast-enhanced ultrasound (CEUS) and shear wave elastography (SWE) features for characterizing serous microcystic adenomas (SMAs): In comparison to pancreatic neuroendocrine tumors (pNETs).

Objectives: Serous microcystic adenoma (SMA), a primary benign pancreatic tumor which can be clinically followed-up instead of undergoing surgery, are sometimes mis-distinguished as pancreatic neuroendocrine tumor (pNET) in regular preoperative imaging examinations. This study aimed to analyze preoperative contrast-enhanced ultrasound (CEUS) and shear wave elastography (SWE) features of SMAs in comparison to pNETs. Material and methods: In this retrospective study, patients with imaging-diagnosed pancreatic lesions were screened between October 2020 to October 2022 (ethical approval No. B2020-309R). Performing by a Siemens Sequoia (Siemens Medical Solutions, Mountain View, CA, USA) equipped with a 5C-1 curved array transducer (3.0-4.5 MHz), CEUS examination was conducted to observe the microvascular perfusion patterns of pancreatic lesions in arterial phase, venous/late phases (VLP) using SonoVue® (Bracco Imaging Spa, Milan, Italy) as the contrast agent. Virtual touch tissue imaging and quantification (VTIQ) - SWE was used to measure the shear wave velocity (SWV, m/s) value to represent the quantitative stiffness of pancreatic lesions. Multivariate logistic regression was performed to analyze potential ultrasound and clinical features in discriminating SMAs and pNETs. Results: Finally, 30 SMA and 40 pNET patients were included. All pancreatic lesions were pathologically proven via biopsy or surgery. During the arterial phase of CEUS, most SMAs and pNETs showed iso- or hyperenhancement (29/30, 97 % and 31/40, 78 %), with a specific early honeycomb enhancement pattern appeared in 14/30 (47 %) SMA lesions. During the VLP, while most of the SMA lesions remained iso- or hyperenhancement (25/30, 83 %), nearly half of the pNET lesions revealed an attenuated hypoenhancement (17/40, 43 %). The proportion of hypoenhancement pattern during the VLP of CEUS differed significantly between SMAs and pNETs (P = 0.021). The measured SWV value of SMAs was significantly higher than pNETs (2.04 ± 0.70 m/s versus 1.42 ± 0.44 m/s, P = 0.002). Taking a SWV value > 1.83 m/s as a cutoff in differentiating SMAs and pNETs, the area under the receiver operating characteristic curve (AUROC) was 0.825, with sensitivity, specificity and likelihood ratio (+) of 85.71 %, 72.73 % and 3.143, respectively. Multivariate logistic regression revealed that SWV value (m/s) of the pancreatic lesion was an independent variable in discriminating SMA and pNET. Conclusion: By comprehensively evaluating CEUS patterns and SWE features, SMA and pNET may be well differentiated before the operation. While SMA typically presents as harder lesion in VTIQ-SWE, exhibiting a specific honeycomb hyperenhancement pattern during the arterial phase of CEUS, pNET is characterized by relative softness, occasionally displaying a wash-out pattern during the VLP of CEUS.

HIF1 contributes to hypoxia-induced pancreatic cancer cells invasion via promoting QSOX1 expression.

BACKGROUND: Quiescin sulfhydryl oxidase 1 (QSOX1), which oxidizes sulfhydryl groups to form disulfide bonds in proteins, is found to be over-expressed in various pancreatic cancer cell lines and patients. QSOX1 promotes invasion of pancreatic cancer cells by activating MMP-2 and MMP-9. However, its regulatory mechanism remains largely undefined. METHODS: Real-time PCR and Western blot were employed to detect the expression of QSOX1 in human pancreatic cancer cell lines under hypoxic condition. Luciferase reporter and ChIP assays were used to assess the regulation of QSOX1 by hypoxia-inducible factor 1 (HIF-1). Small interfering RNA (siRNA) was applied to knock down endogenous expression of QSOX1. Matrigel-coated invasion chamber essays were conducted to detect the invasion capacity of QSOX1-depleted cells. RESULTS: Both hypoxia and hypoxia mimicking reagent up-regulated the expression of QSOX1 in human pancreatic cancer cell lines. Knockdown of HIF-1α eliminated hypoxia induced QSOX1 expression. HIF-1α was found directly bound to two hypoxia-response elements (HRE) of QSOX1 gene, both of which were required for HIF-1 induced QSOX1 expression. Moreover, QSOX1 silencing blocked hypoxia-induced pancreatic cancer cells invasion. CONCLUSION: QSOX1 is a direct target of HIF-1 and may contribute to hypoxia-induced pancreatic cancer cells invasion.

Lipocalin-2 is associated with a good prognosis and reversing epithelial-to-mesenchymal transition in pancreatic cancer.

BACKGROUND: Lipocalin-2 is a multifaceted modulator in cancer progression. Its clinical significance is not clear in pancreatic cancer. The purpose of this study was to investigate whether lipocalin-2 is associated with good prognosis by reversing epithelial-to-mesenchymal transition (EMT) in pancreatic cancer. METHODS: Lipocalin-2, E-cadherin, or vimentin expression was detected in 60 pancreatic adenocarcinoma specimens. Correlations between lipocalin-2 expression and EMT, the clinicopathologic characteristics, and prognosis were investigated. Whether pancreatic cancer cells' migration and invasion (some characteristics of EMT) were affected by lipocalin-2 was also explored. RESULTS: High lipocalin-2 expression was significantly associated with a good prognosis in pancreatic cancer (p < 0.05). Overexpression of lipocalin-2 correlated with a lower extent of EMT (p < 0.05), increased E-cadherin expression (p < 0.05), decreased vimentin expression (p < 0.05), and reduced cancer cell migration and invasion in pancreatic cancer. CONCLUSIONS: Lipocalin-2 may be considered an epithelial inducer, which may reverse EMT and predict a good prognosis in pancreatic cancer.

Pancreatic neuroendocrine tumor: prediction of tumor grades by radiomics models based on ultrasound images.

OBJECTIVE: We aimed to investigate whether the radiomics analysis based on B-mode ultrasound (BMUS) images could predict histopathological tumor grades in pancreatic neuroendocrine tumors (pNETs). METHODS: A total of 64 patients with surgery and histopathologically confirmed pNETs were retrospectively included (34 male and 30 female, mean age 52.4 ± 12.2 years). Patients were divided into training cohort (n = 44) and validation cohort (n = 20). All pNETs were classified into Grade 1 (G1), Grade 2 (G2), and Grade 3 (G3) tumors based on the Ki-67 proliferation index and the mitotic activity according to WHO 2017 criteria. Maximum relevance minimum redundancy, least absolute shrinkage and selection operator were used for feature selection. Receiver operating characteristic curve analysis was used to evaluate the model performance. RESULTS: Finally, 18 G1 pNETs, 35 G2 pNETs, and 11 G3 pNETs patients were included. The radiomic score derived from BMUS images to predict G2/G3 from G1 displayed a good performance with an area under the receiver operating characteristic curve of 0.844 in the training cohort, and 0.833 in the testing cohort. The radiomic score achieved an accuracy of 81.8% in the training cohort and 80.0% in the testing cohort, a sensitivity of 0.750 and 0.786, a specificity of 0.833 and 0.833 in the training/testing cohorts. Clinical benefit of the score also exhibited superior usefulness of the radiomic score, as shown by the decision curve analysis. CONCLUSIONS: Radiomic data constructed from BMUS images have the potential for predicting histopathological tumor grades in patients with pNETs. ADVANCES IN KNOWLEDGE: The radiomic model constructed from BMUS images has the potential for predicting histopathological tumor grades and Ki-67 proliferation indexes in patients with pNETs.

Prediction of Pathological Grades of Pancreatic Neuroendocrine Tumors Based on Dynamic Contrast-Enhanced Ultrasound Quantitative Analysis.

Objective: To investigate whether the dynamic contrast-enhanced ultrasound (DCE-US) analysis and quantitative parameters could be helpful for predicting histopathologic grades of pancreatic neuroendocrine tumors (pNETs). Methods: This retrospective study conducted a comprehensive review of the CEUS database between March 2017 and November 2021 in Zhongshan Hospital, Fudan University. Ultrasound examinations were performed by an ACUSON Sequioa unit equipped with a 3.5 MHz 6C−1 convex array transducer, and an ACUSON OXANA2 unit equipped with a 3.5 MHz 5C−1 convex array transducer. SonoVue® (Bracco Inc., Milan, Italy) was used for all CEUS examinations. Time intensity curves (TICs) and quantitative parameters of DCE-US were created by Vuebox® software (Bracco, Italy). Inclusion criteria were: patients with histopathologically proved pNETs, patients who underwent pancreatic B-mode ultrasounds (BMUS) and CEUS scans one week before surgery or biopsy and had DCE-US imaging documented for more than 2 min, patients with solid or predominantly solid lesions and patients with definite diagnosis of histopathological grades of pNETs. Based on their prognosis, patients were categorized into two groups: pNETs G1/G2 group and pNETs G3/pNECs group. Results: A total of 42 patients who underwent surgery (n = 38) or biopsy (n = 4) and had histopathologically confirmed pNETs were included. According to the WHO 2019 criteria, all pNETs were classified into grade 1 (G1, n = 10), grade 2 (G2, n = 21), or grade 3 (G3)/pancreatic neuroendocrine carcinomas (pNECs) (n = 11), based on the Ki−67 proliferation index and the mitotic activity. The majority of the TICs (27/31) of pNETs G1/G2 were above or equal to those of pancreatic parenchyma in the arterial phase, but most (7/11) pNETs G3/pNECs had TICs below those of pancreatic parenchyma from arterial phase to late phase (p < 0.05). Among all the CEUS quantitative parameters of DCE-US, values of relative rise time (rPE), relative mean transit time (rmTT) and relative area under the curve (rAUC) were significantly higher in pNETs G1/G2 group than those in pNETs G3/pNECs group (p < 0.05). Taking an rPE below 1.09 as the optimal cut-off value, the sensitivity, specificity and accuracy for prediction of pNETs G3/pNECs from G1/G2 were 90.91% [58.70% to 99.80%], 67.64% [48.61% to 83.32%] and 85.78% [74.14% to 97.42%], respectively. Taking rAUC below 0.855 as the optimal cut-off value, the sensitivity, specificity and accuracy for prediction of pNETs G3/pNECs from G1/G2 were 90.91% [66.26% to 99.53%], 83.87% [67.37% to 92.91%] and 94.72% [88.30% to 100.00%], respectively. Conclusions: Dynamic contrast-enhanced ultrasound analysis might be helpful for predicting the pathological grades of pNETs. Among all quantitative parameters, rPE, rmTT and rAUC are potentially useful parameters for predicting G3/pNECs with aggressive behavior.

A special subtype: Revealing the potential intervention and great value of KRAS wildtype pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the predominant form of pancreatic cancer and has devastating consequences on affected families and society. Its dismal prognosis is attributed to poor specificity of symptoms during early stages. It is widely believed that PDAC patients with the wildtype (WT) KRAS gene benefit more from currently available treatments than those with KRAS mutations. The oncogenic genetic changes alternations generally found in KRAS wildtype PDAC are related to either the KRAS pathway or microsatellite instability/mismatch repair deficiency (MSI/dMMR), which enable the application of tailored treatments based on each patient's genetic characteristics. This review focuses on targeted therapies against alternative tumour mechanisms in KRAS WT PDAC.

MR quantitative 3D shape analysis helps to distinguish mucinous cystic neoplasm from serous oligocystic adenoma.

PURPOSE We aimed to assess the performance of quantitative 3D shape analysis in the differential diagno- sis of pancreatic serous oligocystic adenoma (SOA) and mucinous cystic neoplasm (MCN). METHODS Four hundred thirty-two patients diagnosed with serous cystic neoplasms (SCNs) or MCNs were retrospectively reviewed from August 2014 to July 2019 and finally 87 patients with MCNs (n = 45) and SOAs (n = 42) were included. Clinical data and magnetic resonance morphologic fea- tures with 3D shape analysis of lesions (shape sphericity, compacity, and volume) were recorded and compared between MCNs and SOAs according to the pathology. Univariable and multivari- able regression analyses were used to identify independent impact factors for differentiating MCN from SOA. RESULTS The age of MCN patients was younger than SOAs (43.02 ± 10.83 years vs. 52.78 ± 12.31 years; OR = 0.275; 95% CI: 0.098-0.768; P = .014). MCN has a higher female/male ratio than SOA (43/2 vs. 27/15; OR = 40.418; 95% CI: 2.704-604.171; P = .007) and was more often located in the distal of pancreas (OR = 31.403; 95% CI: 2.985-330.342; P = .004). Shape_Sphericity derived from 3D shape analysis was a significant independent factor in the multivariable analysis and the value of MCN was closer to 1 than SOA (OR = 35.153; 95% CI: 5.301-237.585; P < .001). Area under the receiver operating characteristic curve (AUC) of Shape_Sphericity was 0.923 (optimal cutoff value was 0.964876). CONCLUSION Shape_Sphericity in combination with age, sex, and location could help to distinguish MCN from SOA.

Application of dynamic contrast enhanced ultrasound in distinguishing focal-type autoimmune pancreatitis from pancreatic ductal adenocarcinoma.

OBJECTIVE: To explore the value of dynamic contrast enhanced ultrasound (DCE-US) in preoperative differential diagnosis of focal-type autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: From May 2016 to March 2020, patients with biopsy and histopathologically confirmed focal-type AIP (n = 9) were retrospectively included. All patients received contrast enhanced ultrasound (CEUS) examinations one week before surgery/biopsy. Dynamic analysis was performed by VueBox® software (Bracco, Italy). Eighteen cases of resection and histopathologically proved PDAC lesions were also included as control group. B mode ultrasound (BMUS) features, CEUS enhancement patterns, time intensity curves (TICs) and CEUS quantitative parameters were obtained and compared between AIP and PDAC lesions. RESULTS: After injection of ultrasound contrast agents, most focal-type AIP lesions displayed hyper-enhancement (2/9, 22.2%) or iso-enhancement (6/9, 66.7%) during arterial phase of CEUS, while most of PDAC lesions showed hypo-enhancement (88.9%) (P < 0.01). During late phase, most of AIP lesions showed iso-enhancement (8/9, 88.9%), while most of PDAC lesions showed hypo-enhancement (94.4%) (P < 0.001). Compared with PDAC lesions, TICs of AIP lesions showed delayed and higher enhancement. Among all CEUS perfusion parameters, ratio of PE (peak enhancement), WiAUC (wash-in area under the curve), WiR (wash-in rate), WiPI (wash-in perfusion index, WiPI = WiAUC/ rise time), WoAUC (wash-out area under the curve), WiWoAUC (wash-in and wash-out area under the curve) and WoR (wash-out rate) between pancreatic lesion and surrounding normal pancreatic tissue were significantly higher in AIP lesions than PDAC lesions (P < 0.05). CONCLUSION: DCE-US with quantitative analysis has the potential to make preoperative differential diagnosis between focal-type AIP and PDAC non-invasively.

Predictive value of serum carbohydrate antigen 19-9 in malignant intraductal papillary mucinous neoplasms.

BACKGROUND: The goal of the present study was to evaluate the predictive value of serum carbohydrate antigen 19-9 (CA 19-9) in the diagnosis of malignant intraductal papillary mucinous neoplasms of pancreas (IPMNs). METHODS: Eighty-six patients with pathological diagnosis of IPMNs in Zhongshan Hospital between March 1999 and November 2008 were retrospectively reviewed. Data reflecting clinical characteristics, tumor marker level, and prognosis were collected. The potential predictive value of CA 19-9 was analyzed by receiver operating characteristic (ROC) curve. RESULTS: Eighty-six consecutive patients with IPMNs all underwent surgical intervention. A high level of CA 19-9 or carcinoembryonic antigen (CEA) was associated with more advanced stage of malignant IPMNs. Carbohydrate antigen 19-9 was significant for judging malignant IPMNs in the binary logistic regression model (p=0.047). The hazard ratio was 1.014, whose 95.0% confidence interval was 0.91-1.028. Receiver operating characteristic analysis showed that the serum CA 19-9 level had good predictive value for malignant or invasive IPMNs, postoperative survival, and disease-specific recurrence. The area under the curve (AUC) was 0.856, 0.893, 0.815, and 0.857 (p<0.05), respectively. According to the follow-up, mean survival time for groups with CA 19-9>63.60 U/ml was dramatically shorter than that for groups with CA 19-9≤63.60 U/ml (57.38±2.85 versus 29.24±5.82 [months]; p<0.01). CONCLUSIONS: Serum CA 19-9 level has good predictive value for malignant or invasive IPMNs. Patients with CA 19-9 > 63.60 U/ml had poor postoperative prognosis in IPMNs. Preoperative abnormal serum CA 19-9 might be predictive for an aggressive surgical intervention in IPMNs.

[Expression of dihydropyrimidine dehydrogenase negatively correlated with the prognosis of pancreatic ductal adenocarcinoma].

OBJECTIVE: To detect the expression of dihydropyrimidine dehydrogenase (DPD) in pancreatic ductal adenocarcinoma (PDAC), and to investigate the relationships between DPD expression and the prognosis of PDAC. METHODS: Immunohistochemistry and tissue microarray techniques were used to exam the expression of DPD in the cancerous tissue in 156 patients admitted from January 2005 to December 2009, including 89 males and 67 females, with the age ranging from 35 to 81 years. The median age was 55 years. RESULTS: With the positive rate of DPD 55.1%, the expression of DPD was correlated with the differentiation (P = 0.001), TNM staging of tumor (P = 0.021). No relationship was observed between the vessel invasion (P = 0.265), lymphatic metastasis (P = 0.123), neural invasion (P = 0.598) and DPD expression. In the follow-up 117 patients the overall median survival time was 14.2 months, in 58 cases expressed negative, the median survival time was 20.6 months; 39 cases expressed "+" and "++", the median survival time was 12.3 months; 20 cases expressed "+++", the median survival time was 6.8 months. The expression of DPD in pancreatic cancer was correlated with the prognosis of patients, those with higher expression pattern exhibited shorter survival time (P < 0.05). Univariate survival analysis revealed that DPD expression, TNM staging, lymphatic metastasis and neural invasion were factors related to prognosis (P < 0.05), while differentiation levels and vessel invasion were not. Multivariate survival analysis revealed that DPD expression (P = 0.002), lymphatic metastasis (P = 0.000) were two independent prognostic factors. CONCLUSIONS: The expression levels of DPD was correlated to differentiation levels of pancreatic cancer and TNM staging; those with higher expression of DPD showed shorter survival time. DPD expression, lymphatic metastasis were independent prognostic factors for pancreatic cancer.

[Application of serum protein profiling in diagnosis, prognosis and evaluation of curative effect of pancreatic adenocarcinoma].

OBJECTIVE: To establish decision tree and logistic regression classification models for diagnosing pancreatic adenocarcinoma (PaCa) and for screening serum biomarkers related to evaluation of different stages and curative effects. METHODS: Serum samples obtained from subjects with pancreatic adenocarcinoma (n = 58) and normal pancreas (n = 51) were applied to strong anion exchange chromatography (SAX2) chips for protein profiling by SELDI-TOF-MS to screen multiple serum biomarkers. Biomarker Wizard software and several statistical methods including algorithm of decision tree, logistic regression and ROC curves were used to construct the decision tree or logistic regression classification models. RESULTS: Average of 61 mass peaks were detected at the molecular range of 2000-30,000, ten decision trees with the highest cross validation rate were chosen to construct the classification models, which can differentiate PaCa from normal pancreas with a sensitivity of 83.3% and a specificity of 100%. Logistic regression was used to achieve the AUC (0.976 +/- 0.011, P < 0.001) with a sensitivity of 77.6% - 91.4% and a specificity of 92.2% - 100%. Six mass peaks were combined by logistic regression to achieve the AUC 0.897 +/- 0.054, 0.978 +/- 0.021 and 0.792 +/- 0.107 (P < 0.05) in the three groups (patients at stage I and II, stage II and III, stage III and IV). One mass peak (M/Z 4,016) was screened (P < 0.05) significantly between the preoperative and postoperative PaCa samples and the intensity decreased weeks after operation. CONCLUSION: Decision tree and logistic regression classification models of the mass peaks screened by SELDI-TOF-MS serum profiling can be used to differentiate pancreatic adenocarcinoma from normal pancreas, and is superior to CA 199. The detected mass peaks are helpful for the evaluation of curative effect and prognosis of pancreatic adenocarcinoma.

[Clinical implication of BRSK2 expression in pancreatic ductal adenocarcinoma].

OBJECTIVE: To investigate the expression of BRSK2 (brain selective kinase 2) in pancreatic ductal adenocarcinoma and to understand its clinical implication. METHODS: Resected tumor specimens of 79 pancreatic ductal adenocarcinoma were collected and paraffin-embedded for prepare. 0.5 microm sections. Immunohistochemical staining was employed to examine the expression pattern of BRSK2 translated protein. Semi-quantitative analysis was used to evaluate the intensity and content of protein expression in tumor tissues. The expression outcome was compared in peri-tumorous tissues and normal pancreatic tissues. Meanwhile, tumor samples were grouped according to their differentiation, TNM stage, with or without vascular or neural invasion. Then the possible relationship was explored between clinical, pathological and survival data and the expression profile of BRSK2 in tumor tissues. RESULTS: BRSK2's expression was weak in normal pancreatic tissues, including islets and minor ducts such as intercalated ducts, intralobular ducts and interlobular ducts. BRSK2's expression was also weak in peri-tumorous tissues. BRSK2's expression was strong in pancreatic ductal adenocarcinomas. It had a close relationship with lymphatic metastasis, distant metastasis, TNM staging as well as peri-pancreatic neural invasion. Tumors with lymphatic metastasis, distant metastasis and peri-pancreatic neural invasion or at later stages showed a higher expression of BRSK2 than those without or those at early stages. However the expression had no correlation with tumor size, differentiation and vascular invasion. The expression of BRSK2 in pancreatic ductal adenocarcinomas was correlated with the prognosis of patients. Those with a higher expression pattern showed a shorter survival period. CONCLUSION: BRSK2 is up-regulated in pancreatic ductal adenocarcinoma. And its expression is correlated with tumor biological behaviors and patient prognosis.

Magnetic resonance morphologic features predict progression of incidental pancreatic cystic lesions during follow-up.

PURPOSE: We aimed to evaluate which morphologic features on magnetic resonance imaging (MRI) could predict the progression of pancreatic cystic lesions (PCLs) that are suitable for follow-up. METHODS: A total of 2176 MRI findings of PCLs were retrospectively reviewed between January 2009 and December 2016. The study population was composed of 223 patients. Clinical data and morphologic features of PCLs were recorded. We divided the individuals into two sub-groups according to the final features on MRI. Univariable and multivariable regression analyses were performed to identify independent risk factors for progression of PCLs. RESULTS: A total of 84 PCLs (37.7%) progressed during follow-up, while 139 PCLs (62.3%) were stable. Age (odds ratio [OR], 1.042; P = 0.017), number of lesions (OR, 0.491; P = 0.048), communication to pancreatic duct (PD) (OR, 2.425; P = 0.007) and presence of septa (OR, 6.105; P < 0.001) were significant independent factors for progression of PCLs. Among 84 lesions that progressed, 23 lesions (27.4%) increased to ≥ 30 mm in diameter or showed worrisome imaging features at the end of follow-up that needed clinical intervention. The initial size and communication to PD were independent factors for progression of PCLs necessitating clinical intervention (P < 0.001 and P = 0.011, respectively). CONCLUSION: Age, number of the lesions, communication to PD and presence of septa were independent risk factors for the progression of PCLs, and the initial size and communication to PD could potentially predict PCLs needing clinical interventions.

[Comparison of MRI manifestations and histopathologic findings in pancreatic head carcinoma in vivo ex vivo].

OBJECTIVE: To prospectively analyze the correlation of MRI image characteristics with histopathological findings in pancreatic head carcinoma in vivo and ex vivo. METHODS: Sixteen patients with pancreatic head carcinoma were examined by 1.5T MRI. MR sequences included pre-and post-contrast dynamic 2D FLASH T1WI, TSE T2WI + fat suppressed (FS). All fresh specimens were scanned again within an hour after resection during the Whipple procedure, and were then cut into slices along the direction of MRI scan. The MRI image characteristics were compared with gross and histopathologic findings of the specimens. RESULTS: The tumor size ranged from 1.5 cm x 2.0 cm to 4.8 cm x 4.2 cm with a mean value of 3.6 cm x 3.1 cm. The MRI findings in vivo showed hypointensity in 14 lesions and isointensity in 2, and on 2D FLASH T1WI and TSE T2WI, all lesions displayed mixed intensity except 3 lesions with iso-intensity. During post-contrast dynamic pancreatic parenchymal phase, 15 lesions showed mild enhancement and 11 lesions had ring enhancement sign. Nine lesions displayed progressive irregular moderate enhancement during post-contrast dynamic hepatic phase. Four lesions showed enhancement with iso- and hyperintensity in post-contrast dynamic delayed phase. The MRI findings demonstrated that all lesions ex vivo had hypointensity on 2D FLASH T1 WI and mixed intensity on TSE T2WI + FS. Tumor tissues mainly displayed hypointensity, and the area containing tumor and inflammatory tissue showed iso-intensity on 2D FLASH T1WI. On T2WI + FS, the fibrosis proportion displayed hypo or isointensity, while the tumor and chronic inflammatory tissue demonstrated slight hyperintensity, and the zones of mucous degeneration or pancreatic ductal dilatation displayed hyper-intensity. The ring enhancement of tumor was caused by multiple factors and no obvious enhancement within tumor and fibrosis area were observed during post-contrast dynamic pancreatic parenchymal phase. Progressive irregular enhancement originated from desmoplastic reaction within the tumor during post-contrast dynamic hepatic phase and delayed phase, respectively. CONCLUSION: Pancreatic head carcinomas contain various kinds of tissues. MRI can reveal these pathologic characteristics. No obvious hemorrhage and necrosis within the tumor were observed in this series.