Usefulness of endoscopic ultrasound for acquiring the pathological diagnosis of gastrointestinal lymphoma.

BACKGROUND AND STUDY AIMS: This study aims to assess the value of endoscopic ultrasound (EUS) for acquiring a pathological diagnosis of gastrointestinal lymphoma (GIL). PATIENTS AND METHODS: We retrospectively reviewed all GIL patients who underwent EUS from November 2011 to July 2020 at Fudan University Shanghai Cancer Center. All patients with pathologically confirmed GIL were included. The characteristics of the lesions were recorded, and the efficacy for acquiring pathologic diagnosis between white light endoscopy (WLE) and EUS was analyzed. RESULTS: In total, 404 patients with GIL who underwent EUS examination were included in this study. GIL was confirmed in 143 cases by after EUS judgment biopsy (AEJ biopsy), 11 cases by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), 293 cases by WLE biopsy, and 10 cases by surgical pathology for repeated negative pathologic results from EUS and WLE. Among all cases, 78.71% (318/404) were T1-T2, whereas 32.18% (130/404) were determined to have multiple lesions in the digestive tract wall. The positive rates of the WLE biopsy and AEJ biopsy of the involved gastric wall were 77.93% (293/376) and 89.38% (143/160), respectively. Twelve cases showed diffuse thickening of the gastric wall, and the total positive rate of EUS was 91.67% but 0% for WLE with this type of GIL. The total positive rate and positive rate during the first examination of EUS were all significantly higher than those of WLE. Moreover, 19.68% of the patients showed negative results during their WLE examination and then received a positive pathologic diagnosis upon EUS examination, but none had the opposite process. CONCLUSIONS: EUS was found to be a better tool for acquiring a pathological diagnosis of GIL than conventional WLE, especially for GIL similar to linitis plastica.

Novel Branched-Chain Amino Acid-Catabolism Related Gene Signature for Overall Survival Prediction of Pancreatic Carcinoma.

Branched-chain amino acid (BCAA) metabolism plays an important role in the pancreatic carcinogenesis, but its mechanism remains unclear. Hence, this study was performed to investigate the value of genes related to BCAA catabolism in pancreatic cancer. The online Gene Expression Omnibus database, The Cancer Genome Atlas, and International Cancer Genome Consortium data sets were searched for bioinformatic analysis. Univariate Cox and Lasso regression were applied to construct a predictive model. Human cancer cell lines and tissue microarray (TMA) were applied for validation. From the 48 BCAA-catabolism enzyme (BCE) genes, a 5-gene risk-score (ABAT, ACAT1, BCAT1, BCAT2, and DBT) was constructed. Patients in high-risk and low-risk groups stratified by risk-score indicated significantly different overall survival. Given the clinical parameters, the risk-score was an independent predictor for prognosis. Among the five genes, BCAT2 and ABAT were hub genes with favorable prognosis value, which was validated by TMA immunohistochemistry (IHC) staining. Immune infiltration analysis indicated high-risk group enriched macrophage, and decreased positive cell density of stromal CD68+ macrophage in TMA was observed for BCAT2 with low-expression versus high-expression cases. In conclusion, a risk-score involving five BCE genes was proposed to predict the poor prognosis of pancreatic cancer. On the basis of the immune infiltration analysis, the underlying mechanism might be BCAT2 associated stromal macrophage infiltration.

Integrated Analysis of the Immune Infiltrates and PD-L1 Expression of N6-Methyladenosine-Related Long Non-Coding RNAs in Colorectal Cancer.

BACKGROUND: N6-methyladenosine-related long non-coding RNAs (m6A-related lncRNAs) are involved in the occurrence and progression of various cancers. However, it remains unclear whether m6A-related lncRNAs have potential roles in tumor immune microenvironment (TIME). METHODS: Herein, we investigated correlations of prominent m6A-related lncRNAs with immune infiltrates and PD-L1 expression and the prognostic value of m6A-related lncRNAs in colorectal cancer from The Cancer Genome Atlas (TCGA) cohort, systematically. RESULTS: Firstly, we conducted Pearson correlation analysis to screen the m6A-related lncRNAs, and then univariate Cox regression analysis was performed to identify 72 prognostic m6A-related lncRNAs in CRC patients. Moreover, two molecular subtypes (cluster 1/2) were identified by consensus clustering for 72 m6A-related lncRNAs. The cluster 1 preferentially associated with favorable prognosis, upregulated PD-L1 expression, higher immunoscore, and distinct immune cell infiltration. Furthermore, a prognostic risk score was calculated using 19 m6A-related lncRNAs based signatures which represented an independent prognostic factor for CRC. Patients with low-risk score showed higher PD-L1 expression than patients with high-risk score. Further analysis revealed that m6A-related lncRNAs based signatures were associated with tumor-infiltrating immune cells. CONCLUSION: Our study indicated the essential roles of m6A-related lncRNAs in TIME of CRC and provide novel insights in our understanding of m6A-related lncRNAs function in colorectal cancer.

Differentiation of solid-pseudopapillary tumors of the pancreas from pancreatic neuroendocrine tumors by using endoscopic ultrasound.

BACKGROUND AND AIM: To differentiate solid-pseudopapillary tumors (SPTs) of the pancreas from pancreatic neuroendocrine tumors (pNETs) by endoscopic ultrasound. METHODS: We retrospectively reviewed all patients with SPTs and pNETs who underwent endoscopic ultrasound (EUS) from May 2012 to August 2018 at the Fudan University Shanghai Cancer Center. We included patients confirmed pathologically with a surgical biopsy or with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The demographic data of the patients, characteristics of the lesions and overall survival data of patients with these two diseases were further compared. RESULTS: A total of 147 pNET patients and 21 SPT patients were included in our study. The mean ages of the patients in the SPT and pNET groups were 35.95years and 54.30years, respectively. There were more females in the SPT group than in the pNET group (71.43% vs. 40.82%). The patients in the pNET group had significantly more lymphatic metastases and visceral organ metastases than the patients in the SPT group. A larger proportion of pNET lesions than SPT lesions had homogeneous echo patterns and were hypervascular. Cystic components and calcification components were more often observed in the SPT lesions than in the pNET lesions. In the multivariate logistic regression analysis, the hypervascularization (OR: 6.528, 95% CI: 1.562-27.285, P=0.010) and cystic component (OR: 0.106, 95% CI: 0.019-0.597, P=0.011) variables resulted in the best discrimination of patients with SPTs from patients with pNETs. Survival among patients with SPTs was higher than that among patients with pNETs at all points in the follow-up period. CONCLUSIONS: SPTs tended to occur in younger people and were more common in women. Pancreatic neuroendocrine tumors tended to form metastases more often than SPTs. The blood supply and cystic components of the lesions may have novel potential diagnostic utility for differentiating SPTs from pNETs.

The Strain Ratio as Obtained by Endoscopic Ultrasonography Elastography Correlates With the Stroma Proportion and the Prognosis of Local Pancreatic Cancer.

OBJECTIVE: The aim of this study was to investigate the association of the strain ratio (SR) with clinicopathologic features and the prognostic value of the SR in local pancreatic cancer. BACKGROUND: The SR as obtained by endoscopic ultrasonography elastography is useful in the differential diagnosis of pancreatic diseases. However, its role in the prognostic prediction of pancreatic cancer remains unknown. METHODS: A total of 78 resected pancreatic cancer patients and 93 locally advanced pancreatic cancer (LAPC) patients were enrolled in this study according to the inclusion criteria. Masson trichrome staining was used to evaluate the stromal proportion. Survival rates were calculated according to the Kaplan-Meier method and were compared using the log rank test. Multivariate analysis was performed with a Cox regression model. RESULTS: The SR was positively associated with the stromal proportion of resected pancreatic cancer (R = 0.768, P < 0.001). High SR was more likely in males (P = 0.039) and was related to perineural invasion (P = 0.022). High SR predicted unfavorable overall survival (OS) relative to low SR (15.4 vs. 25.8 mo, P = 0.017). SR was confirmed as an independent prognostic factor for resected pancreatic cancer based on multivariate analysis (hazard ratio = 1.939, P = 0.020). For LAPC patients who received nab-paclitaxel and gemcitabine, high SR was associated with improved prognosis (OS: 14.9 vs. 11.6 mo, P = 0.045), but this positive association was not observed in patients treated with other gemcitabine-based regimens (OS: 10.7 vs. 12.4 mo, P = 0.478). CONCLUSIONS: A high SR as obtained by endoscopic ultrasonography elastography was associated with poor prognosis of resected pancreatic cancer but predicted improved survival for LAPC patients treated with the nab-paclitaxel and gemcitabine regimen.

Validation and head-to-head comparison of four models for predicting malignancy of intraductal papillary mucinous neoplasm of the pancreas: A study based on endoscopic ultrasound findings.

BACKGROUND: Several models are currently available for predicting the malignancy of pancreatic intraductal papillary mucinous neoplasm (IPMN), namely, the Pancreatic Surgery Consortium (PSC), the Japan Pancreas Society (JPS), the Johns Hopkins Hospital (JHH), and the Japan-Korea (JPN-KOR) models. However, a head-to-head comparison that shows which model is more accurate for this individualized prediction is lacking. AIM: To perform a head-to-head comparison of the four models for predicting the malignancy of pancreatic IPMN. METHODS: A total of 181 patients with IPMN who had undergone surgical resection were identified from a prospectively maintained database. The characteristics of IPMN in patients were recorded from endoscopic ultrasound imaging data and report archives. The performance of all four models was examined using Harrell's concordance index (C-index), calibration plots, decision curve analyses, and diagnostic tests. RESULTS: Of the 181 included patients, 94 were categorized as having benign disease, and the remaining 87 were categorized as having malignant disease. The C-indexes were 0.842 [95% confidence interval (CI): 0.782-0.901], 0.704 (95%CI: 0.626-0.782), 0.754 (95%CI: 0.684-0.824), and 0.650 (95%CI: 0.483-0.817) for the PSC, JPS, JHH, and JPN-KOR models, respectively. Calibration plots showed that the PSC model had the least pronounced departure from ideal predictions. Of the remaining three models, the JPS and JHH models underestimated the probability of malignancy, while the JPN-KOR model overestimated the malignant potential of branch duct-IPMN. Decision curve analysis revealed that the PSC model resulted in a better clinical net benefit than the three other models. Diagnostic tests also showed a higher accuracy (0.801) for the PSC model. CONCLUSION: The PSC model exhibited the best performance characteristics. Therefore, the PSC model should be considered the best tool for the individualized prediction of malignancy in patients with pancreatic IPMN.

Gene signature associated with neuro-endocrine activity predicting prognosis of pancreatic carcinoma.

BACKGROUND: Genomic analysis is the promising tool to clear understanding of the tumorigenesis and guide molecular classification for pancreatic cancer. Our purpose was to develop a critical predictive model for prognosis in pancreatic carcinoma, based on the genomic data. METHODS: The online The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets were queried as training and validation cohorts for comprehensive bioinformatic analysis. We applied Lasso and multivariate Cox regression to shrink genes and construct predictive model. RESULTS: A four genes model (DNAH10: HR = 0.71, 95% CI = 0.57-0.88, HSBP1L1: HR = 1.51, 95% CI = 1.18-1.92, KIAA0513: HR = 0.69, 95% CI = 0.50-0.96, and MRPL3: HR = 3.73, 95% CI = 2.03-6.86), was proposed and validated. The C-index was 0.73 (95% CI: 0.7-0.77). Patients in high-risk and low-risk group, stratified by model, suffered significantly different overall survival time (15.1 vs. 49.3 months, p < 0.0001 in TCGA; 423 vs. 618 days, p = 0.038 in ICGC). Taken clinical parameters into consideration, the risk-score was independent marker in clinical subpopulation. To explore the molecular mechanisms, 579 differential expression genes (DEG) in two groups were identified by edgeR. Functional enrichment of DEG indicated neuro-endocrine activity was the potential mechanism for the discrepant prognosis. CONCLUSION: A specific four genes signature with the ability to predicted survival of pancreatic carcinoma was generated, which may indicate the connection between neuro-endocrine activity and patients' prognosis.

Endoscopic ultrasound-guided fine-needle aspiration used in diagnosing gastric linitis plastica: Metastatic lymph nodes can be valuable targets.

BACKGROUND AND AIM: The aim of this study was to assess the performance of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the diagnosis of gastric linitis plastic (GLP). METHODS: We retrospectively reviewed all the cases undergoing EUS for suspected GLP from January 2012 to September 2017. We included patients with GLP confirmed pathologically with white-light endoscopy (WLE)-guided biopsy or EUS-FNA. Diagnostic value of WLE biopsy and EUS-FNA was further analyzed. RESULTS: A total of 107 cases of suspected GLP were referred for EUS examination in our center. Twenty-six patients were eligible and included. GLP was confirmed in 15 cases by EUS-FNA, nine cases by WLE biopsy, and eight cases by surgical pathology. The positive rate of EUS-FNA and WLE biopsy for involved gastric wall was 71.43% (15/21) and 47.37% (9/19). EUS-FNA of metastatic lymph nodes was also performed in 16 cases, and 15 (93.75%) were proved to be malignant, including all 13 that were positive for peri-gastric lymph nodes, and two of three (66.67%) that were positive rate for retroperitoneal lymph nodes. Diameters of punctured lymph nodes ranged from 3.30 to 22.70 mm, with an average of 12.12 mm. CONCLUSIONS: Pathological diagnosis of GLP by invasive endoscopy is still intractable, even at a late stage. Positive results can be obtained even in small or distant lymph nodes.

Endoscopic ultrasonography guided transgastric trans-portal system fine needle aspiration for diagnosing pancreatic head and uncinate process malignancy.

BACKGROUND: Endoscopic ultrasonography guided fine needle aspiration (EUS-FNA) is a well-established technique for diagnosing pancreatic malignancy. In general, tissue of pancreatic head and uncinate process lesions is obtained via a transduodenal approach. However, this tissue-acquisition modality is not applicable in cases of pyloric obstruction and duodenal bulb ulceration. The aim of this study is to determine the feasibility and safety of a novel EUS-guided transgastric trans-portal system FNA in the diagnosis of pancreatic head and uncinate process cancer. METHODS: This study retrospectively analyzed 26 consecutive inpatient patients who had undergone EUS-FNA for highly suspected malignancy of pancreatic head or uncinate process between December 2013 and December 2018. EUS-guided transgastric trans-portal vein (trans-PV, n=2) or trans-superior mesenteric vein (trans-SMV, n=24) FNA was performed in the patients under conscious sedation. Feasibility, diagnostic yield and complication rates of the technique were evaluated. RESULTS: Specimens obtained by EUS-guided transgastric trans-portal system FNA were adequate for cytological evaluation in all 26 patients. Cytological diagnosis of adenocarcinoma was established in 22 patients, while the remaining 4 patients were negative. The diagnostic accuracy, sensitivity and specificity were 92.3%, 91.7% and 100% respectively. No immediate or delayed procedure-related complications were observed. CONCLUSIONS: EUS-guided transgastric trans-portal system FNA is a feasible and probably safe method for diagnosing pancreatic head and uncinate process malignancy. Careful selection of the potential candidates and close periprocedural observation are mandatory.

Simple Vascular Architecture Classification in Predicting Pancreatic Neuroendocrine Tumor Grade and Prognosis.

BACKGROUND AND AIM: Vascularity is a critical feature in the evaluation of pancreatic neuroendocrine tumor (PNET). When done by EUS, contrast agents are recommended. However, vascular architecture (VA) can also be evaluated by routine Doppler flow in EUS without contrast agents. Our aim was to provide a simple VA classification in EUS for PNET grade and prognosis. METHODS: All pathologically proven PNET cases with EUS between 2012 and 2018 were retrospectively analyzed. The Doppler imaging was retrieved for VA classification. Predictive model construction was performed by machine learning algorithms. RESULTS: A total of 112 PNET cases were evaluated, among which 93 cases were subjected to VA classification. The VA was classified into type A (peritumoral with or without intratumoral vessels [A1 or A2]); type B (only intratumoral vessels); and type C (flow was absent). The VA classification was significantly correlated with tumor grades: 74% type A1 was G1, 73% type B was G2, and 58% type C was G3. Multivariate analysis indicated that elevated serum CA19-9 and type C classification were the independent predictors of G3 tumor. Five machine learning models were constructed, among which random forest was the best one with an AUC of 0.9972. Low-risk patients classified by this model exhibited better prognosis than high-risk patients (p = 0.0087). CONCLUSIONS: In the novel simple VA classification, peritumoral, intratumoral, and absent vessels are prone to be G1, G2, and G3, respectively. Combined with serum CA19-9 and lesion size, the VA classification could predict tumor grade and prognosis in PNET.

Analysis of Fine-Needle Biopsy vs Fine-Needle Aspiration in Diagnosis of Pancreatic and Abdominal Masses: A Prospective, Multicenter, Randomized Controlled Trial.

BACKGROUND & AIMS: Endoscopic ultrasound (EUS)-guided fine needles with side fenestrations are used to collect aspirates for cytology analysis and biopsy samples for histologic analysis. We conducted a large, multicenter study to compare the accuracy of diagnosis via specimens collected with fine-needle biopsy (FNB) versus fine-needle aspiration (FNA) for patients with pancreatic and nonpancreatic masses. METHODS: We performed a prospective single-blind study at 5 tertiary care centers in China. The study comprised 408 patients undergoing EUS for a solid mass (>1 cm) in the pancreas, abdomen, mediastinum, or pelvic cavity, from December 2014 through January 2016. Patients were randomly assigned to groups (1:1) for assessment by FNA (n = 190) or FNB (n = 187). After lesions were identified by EUS, samples were collected in a total of 4 passes by each needle. All procedures were performed by experienced endosonographers; cytologists and pathologists were blinded to the sample collection method. Patients were followed for at least 48 weeks, and final diagnoses were obtained after surgery, imaging analysis, or resolution of lesion. The primary aim was to compare diagnostic yields of EUS-FNA with EUS-FNB for all solid masses, then separately as pancreatic and nonpancreatic masses. The secondary endpoint was the quality of histologic specimen. RESULTS: Findings from FNB analysis were accurate for 91.44% of all cases, compared with 80.00% for all FNA cases, based on final patient diagnoses (P = .0015). In patients with pancreatic masses (n = 249), findings from histologic analysis of FNBs were accurate for 92.68% of the cases, compared with 81.75% for FNAs (P = .0099). In cytology analysis of pancreatic masses, samples collected by FNB accurately identified 88.62% of all pancreatic lesions, whereas samples collected by FNA accurately identified 79.37% (P = .00468). Analyses of samples of nonpancreatic masses collected by FNA versus FNB produced similar diagnostic yields. CONCLUSIONS: In a prospective study of patients with pancreatic masses, we found EUS-guided FNB samples to produce more accurate diagnoses than samples collected by EUS-guided FNA samples. No difference in diagnostic yield was seen between EUS-FNA and EUS-FNB for nonpancreatic masses. Clinical Trials.gov no: NCT02327065.

Endoscopic ultrasound-guided cutting of holes and deep biopsy for diagnosis of gastric infiltrative tumors and gastrointestinal submucosal tumors using a novel vertical diathermic loop.

AIM: To report on a more accurate diagnostic possibility offered by endoscopic ultrasound-guided cutting of holes and deep biopsy (EUS-CHDB) for pathologic diagnosis of gastric infiltrative tumors and gastrointestinal submucosal tumors. METHODS: Ten consecutive patients who were suspected of having gastric invasive tumors or gastrointestinal submucosal tumors underwent EUS-CHDB with a novel vertical diathermic loop. We reviewed their medical data and analysed the effectiveness and safety of this new method. The final diagnosis was based on the surgical pathology or clinical/imaging follow-up. RESULTS: EUS-CHDB was performed successfully in all the ten patients. Neither severe haemorrhage nor perforation occurred in any patient. Among the ten patients, there were three cases of gastric linitis plastica, one case of gastric lymphoma, five cases of gastrointestinal stromal tumors (GISTs), and only one case of chronic non-atrophic gastritis. That is, nine (90%) of the cases treated by EUS-CHDB showed positive findings. CONCLUSION: EUS-CHDB may be a technically feasible and safe option for patients with gastric infiltrative tumors or gastrointestinal submucosal tumors. EUS-CHDB may be used as a remedial or even preferred biopsy method for submucosal lesions.

Can MDCT or EUS features predict the histopathological grading scheme of pancreatic neuroendocrine neoplasms?

PURPOSE: To identify whether the features of preoperative MDCT or EUS could predict the histopathological grading scheme of pancreatic neuroendocrine neoplasms (pNENs). METHODS: A total of 25 patients with pNENs were enrolled in the present study. The qualitative and quantitative variables were reviewed. The qualitative variables included location, contour, border, necrosis, intratumoral vessel, homogeneity, calcification, peripancreatic fat/vessel infiltration, pancreatic duct dilatation, mass within pancreas, lymphadenopathy and hepatic metastasis on MDCT and border, echogenicity, cystic/solid and blood flow on EUS. The quantitative variables included long diameter (LD), short diameter (SD), unenhanced mass attenuation (UMA), unenhanced pancreatic attenuation (UPA), arterial phase mass attenuation (APMA), arterial phase pancreatic attenuation (APPA), portal venous phase mass attenuation (PVPMA), portal venous phase pancreatic attenuation (PVPPA), arterial phase enhancement degree (APED) and portal venous phase enhancement degree (PVPED). In addition, sex and age were also evaluated. Histopathological classifications met the criterion of 2010 edition WHO Histopathological Classifications. Kruskal-Wallis test and Boruta algorithm were conducted. RESULTS: Lymphadenopathy and peripancreatic fat or vascular invasion foretold higher histopathological grading level while well-defined border on EUS image lower grading level. CONCLUSIONS: Lymphadenopathy, border on EUS image and peripancreatic fat or vascular invasion can predict the histopathological grading scheme of pNENs.

Probe-based confocal laser endomicroscopy for the diagnosis of undetermined biliary stenoses: A meta-analysis.

BACKGROUND: Presently, both the accuracy and sensitivity for distinguishing biliary stenosis from benign to malignant are low. In recent articles, the probe-based confocal laser endomicroscopy (pCLE) showed a better sensitivity than traditional methods in diagnosing malignant biliary stenosis. Here, we conducted a meta-analysis to summarise the published literature. METHODS: A systematic search for literature was conducted in the Medline, Embase and Cochrane Library databases published until November 2015. Further publications were found in the reference lists of the relevant articles. A quality assessment and data extraction were performed by two reviewers independently. A meta-analysis was performed to evaluate the diagnostic efficiency of a pCLE for discriminating benign and malignant biliary stenoses. RESULTS: Eight studies involving 280 patients were included in the analysis. Significant heterogeneity in specificity was observed among the studies (Cochran's Q test=15.89, degrees of freedom [df]=7, P=0.0261 and I2=55.9%), while the heterogeneity in sensitivity was not obvious (Cochran's Q test=7.99, df=7, P=0.3334 and I2=12.4%). The area under the summary receiver operating characteristic (SROC) curve was 0.8968. The meta-regression and subgroup analysis indicated that the outlier was the source of heterogeneity. When analysed in the random-effects model, the pooled sensitivity, specificity, positive likelihood ratio (LR) and negative LR were 0.90 (0.84-0.94), 0.75 (0.66-0.83), 3.17 (2.18-4.61) and 0.17 (0.11-0.26), respectively. No significant publication bias was found in our research. CONCLUSION: A pCLE is a valuable method for the differential diagnosis between malignant and benign biliary stenoses. However, a preferable diagnostic standard should be explored and improvements in specificity are required.

Suppression effects of negative pressure on the proliferation and metastasis in human pancreatic cancer cells.

BACKGROUND AND AIMS: The aim was to explore the effect of negative pressure on the proliferation and metastasis of human pancreatic cancer SW1990 cells. SETTINGS AND DESIGN: Three groups were conducted in the work: normal control group (NC group, 0 mm Hg), low negative pressure group (LN group, -300 mm Hg), and high negative pressure group (HN group, -600 mm Hg). MATERIALS AND METHODS: Cell morphological assay was conducted using an inverted Nikon TE2000-S microscope. Cell viability was assayed using cell counting kit-8 solution. Cell apoptosis was evaluated with flow cytometry. Cell migration was investigated using transwell assay. RESULTS: Compared to LN and HN groups, SW1990 cells in NC group grew quite well, showing a higher density. The NC group represented the highest cell viability. The HN group represented the lowest cell viability, which was lower than that of the LN group (P < 0.01). The apoptosis rate in NC group, LN group and HN group was 1.91% ± 0.13%, 2.31% ± 0.06% and 15.22% ± 0.81%, respectively (P < 0.05). The average number of migration cells in NC group was 53.60 ± 4.14 (× 200), which was decreased to 18.93 ± 3.67 and 11.07 ± 3.01 in LN group and HN group, respectively (P < 0.01). CONCLUSION: The negative pressure shows suppression effects on the proliferation and metastasis of human pancreatic cancer SW1990 cells. It is indicated that negative pressure may be involved in the development of human pancreatic cancer by influencing cell biological characteristics.

Impact of inconclusive endoscopic ultrasound-guided fine-needle aspiration results in the management and outcome of patients with solid pancreatic masses.

BACKGROUND AND AIM: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) can be inconclusive in diagnosing solid pancreatic masses. The aim of the present study was to evaluate the impact of an inconclusive EUS-FNA in the management of patients with solid pancreatic masses. METHODS: This is a retrospective analysis of a prospective database of patients with solid pancreatic masses referred for EUS-FNA between December 2011 and December 2013. Consecutive patients with inconclusive initial EUS-FNA were included. Demographic, clinical, procedural and outcome data were analyzed. RESULTS: Over the study period, 387 patients underwent EUS-FNA of solid pancreatic masses, of which 38 patients had inconclusive cytology. Of the 38 patients, 18 were categorized as atypical, two were categorized as indeterminate or suspicious for malignancy, and 18 were categorized as benign process. Subsequently, 24 (63.2%) patients achieved cytopathological diagnosis by repeat EUS-FNA (8), transcutaneous FNA (4) and surgery (12). Repeat EUS-FNA were done a median of 13 days after the index examination and resulted in conclusive diagnosis in 72.7% of cases. Five patients undergoing surgery were confirmed to have benign lesions. In 14 (36.8%) patients not receiving a positive cytopathological diagnosis, 11 were eventually confirmed to be malignant based on clinical outcome and imaging evidence. CONCLUSIONS: Inconclusive EUS-FNA could lead to unnecessary surgical procedures in patients with resectable solid pancreatic masses if no cytopathological diagnosis is obtained through either repeat or alternative diagnostic modalities. Repeat EUS-FNA provided a conclusive diagnosis in a majority of cases, and therefore should be strongly considered ahead of other modalities.

Incidence of hyperamylasemia after endoscopic ultrasound-guided fine needle aspiration of pancreatic lesions: a multicenter study from China.

OBJECTIVES: There have been few reports regarding the incidence of hyperamylasemia after endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). In particular, the potential risk factors involved in the development of hyperamylasemia have not been analyzed owing to the small number of cases reported. The aim of this study was to evaluate hyperamylasemia and associated risk factors after EUS-FNA of a large sample of pancreatic lesions. METHODS: Patients who underwent EUS-FNA for treatment of a pancreatic lesion were recruited from 6 medical centers in China. RESULTS: A total of 1023 patients presenting with pancreatic lesions between January 2004 and June 2008 were enrolled in this study, with 48 (4.7%) of the 1023 patients presenting with hyperamylasemia 3 hours after the procedure. These patients had a mean ± SD serum amylase level of 331.64 ± 138.60 UI/L. With the use of unconditional logistic regression analysis, the incidence of hyperamylasemia was found to be affected by the type of cystic lesion present and the gauge of the needle used. In 4 (0.4%) of the 1023 patients, acute pancreatitis developed. CONCLUSIONS: The overall incidence of hyperamylasemia after EUS-FNA is relatively low. However, the type of cystic lesion present and the gauge of the needle (19G) used for EUS-FNA may represent risk factors for the incidence of hyperamylasemia.

A minimally invasive alternative for managing large pancreatic duct stones using a modified expandable metal mesh stent.

BACKGROUND AND AIM: Endoscopic clearance of large or impacted stones in the main pancreatic duct (MPD) remains a clinical challenge. In this study, we attempted to technically modify the metallic stent to facilitate the clearance of large pancreatic stones in 4 patients, hoping to lower the operative risks and shorten hospital stay. PATIENTS AND METHODS: Four patients with chronic pancreatitis and large stones in the MPD received endoscopic treatment. Inclusion criteria were: (1) pancreatic intraductal stones (number >3; diameter >or=10 mm) and strictures identified in the distal MPD; (2) calculi mainly located in the head, neck and/or body of the pancreas, and (3) failed clearance of stones using a balloon catheter or Dormia basket. Before clearing the pancreatic calculi completely, a technically modified uncovered self-expandable metallic pancreatic stent was implanted in the MPD for 4-7 days to dilate the ductal stenosis, and then drawn out through the working channel. RESULTS: As the MPD had been sufficiently expanded by the stent, the calculi were removed completely and uneventfully by the balloon or Dormia basket in all 4 patients, without inducing major postoperative complications. A 9- to 15-month follow-up did not find major complications or recurrence of large calculi in the MPD. CONCLUSIONS: Technically modified metallic stenting is a minimally invasive and clinically feasible alternative to extracorporeal shock wave lithotripsy in the management of large pancreatic duct stones.

Treatment of experimental hepatic fibrosis by combinational delivery of urokinase-type plasminogen activator and hepatocyte growth factor genes.

PURPOSE: To investigate the effect of combinational delivery of urokinase-type plasminogen activator (uPA) and hepatocyte growth factor (HGF) genes on hepatic fibrosis. METHODS: Replication-deficient adenoviral vectors expressing either human HGF (AdHGF) or uPA (AduPA) were generated. HGF gene was transferred into primary cultured hepatocytes and uPA gene to hepatic stellate cell (HSC) to investigate the effect on the biological character of cells. Combinational adenoviruses were infused into hepatic fibrosis rats. Serum markers as well as histological and immunohistochemical examination were carried out to test the reversal of hepatic fibrosis. RESULTS: Transfection of exogenous HGF gene induced expression of c-met/HGF receptor and stimulated hepatocyte proliferation. uPA gene delivered into HSC decreased the amount of collagen types I and III accompanied with the increased expression of matrix metalloproteinase-2. In vivo, the area of extracellular matrix in the fibrotic liver decreased to 72% in AdHGF-treated rats (P<0.01), 64% in the AduPA-treated group (P<0.01), and 51% in bi-genes transfection (P<0.01), compared with that of the controls. Moreover, immunohistochemical staining of collagen types I and III revealed that combinational genes delivery exerted more effect on reversal of hepatic fibrosis than mono-gene transfection. CONCLUSIONS: Our study indicated that simultaneous delivery of two antifibrotic genes could confer synergistic effect on hepatic fibrosis.