The clinical impact of endoscopic ultrasound-guided fine-needle aspiration on the patients with low-risk pancreatic cystic lesions.

Background and aims: Endoscopic ultrasound (EUS) is playing a more and more important role in the management of pancreatic cystic lesion (PCLs). The aim of our study was to evaluate the clinical impact of EUS and EUS guided fine needle aspiration (FNA) on patients with low-risk PCLs. Materials and methods: Low-risk PCL patients who underwent EUS-FNA in 2 edoscopic centers were retrospectively collected and analyzed. The clinical impact of EUS-FNA on these patients was analyzed and the predictors for significance EUS-FNA (defined by diagnosis and treatment method change, new high-risk feature identified after imaging scans) were analyzed by logistic regression analyses. Results: From July 2004 to February 2017, 186 patients with low-risk PCLs were included. The study cohort had a mean age of 52.4 ± 15.9 years (range: 19-86 years) with 89 (47.8%) male patients included. The clinical significance of EUS-FNAs was observed in 74 patients (39.8%). The presumed diagnoses of PCLs by imaging were changed in 51 (51/74, 68.9%) patients. Nineteen (19/74, 25.7%) new high-risk features were identified by EUS-FNA, and four patients (4/74, 5.4%) underwent surgery due to suspicious or malignant cytology. Based on multivariate analysis, large cyst size [odds ratio (OR): 1.12, 95% confidence interval (CI): 1.02-1.19, P = 0.033], young age (OR: 0.94, 95% CI: 0.91-0.99, P = 0.041) and BMI over 25 (OR: 3.15, 95% CI: 1.29-7.86, P = 0.013) were independent predictors of clinical significance for EUS-FNA. The optimal age and cyst size to predict significance EUS-FNA was 46.0 years and 2.3cm. Conclusions: On the basis of a 2-center retrospective study, EUS-FNA was clinically significant in about 40% of low-risk PCLs, especially in young, large cyst size, and overweight patients.

A novel Joint-Net model for recognizing small-bowel polyp images.

INTRODUCTION: To automatically recognize polyps of enteroscopy images and avoid pathological change, a novel Joint-Net has been proposed. MATERIAL AND METHODS: The left half of the Joint-Net is constructed by transfer learning VGG16 and its right half is deepened based on the U-Net. In the previous two skip connections, a 3 × 3 convolution layer is added and the original two convolutions are replaced by the identity blocks. To connect the left and the right half part, the asymmetric convolution layer is used. In the output, the loophole-like structure is used. RESULTS: The enteroscopy images were obtained in Changhai Hospital of Shanghai. The mean values of Dice and intersection over union were 90.05% and 82.71%. The classification accuracy of normal images and polyp images was 93.50%. CONCLUSIONS: The experiments show that the Joint-Net can segment and recognize the polyps successfully.

Validation of serum tumor biomarkers in predicting advanced cystic mucinous neoplasm of the pancreas.

BACKGROUND: Early detection of advanced cystic mucinous neoplasms [(A-cMNs), defined as high-grade dysplasia or malignancy] of the pancreas is of great significance. As a simple and feasible detection method, serum tumor markers (STMs) may be used to predict advanced intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs). However, there are few studies on the usefulness of STMs other than carbohydrate antigen (CA) 19-9 for early detection of A-cMNs. AIM: To study the ability of five STMs-CA19-9, carcinoembryonic antigen (CEA), CA125, CA724, and CA242 to predict A-cMNs and distinguish IPMNs and MCNs. METHODS: We mainly measured the levels of each STM in patients pathologically diagnosed with cMNs. The mean levels of STMs and the number of A-cMN subjects with a higher STM level than the cutoff were compared respectively to identify the ability of STMs to predict A-cMNs and distinguish MCNs from IPMNs. A receiver operating characteristic curve with the area under curve (AUC) was also created to identify the performance of the five STMs. RESULTS: A total of 187 patients with cMNs were identified and 72 of them showed A-cMNs. We found that CA19-9 exhibited the highest sensitivity (SE) (54.2%) and accuracy (76.5%) and a moderate ability (AUC = 0.766) to predict A-cMNs. In predicting high-grade dysplasia IPMNs, the SE of CA19-9 decreased to 38.5%. The ability of CEA, CA125, and CA724 to predict A-cMNs was low (AUC = 0.651, 0.583, and 0.618, respectively). The predictive ability of CA242 was not identified. The combination of STMs improved the SE to 62.5%. CA125 may be specific to the diagnosis of advanced MCNs. CONCLUSION: CA19-9 has a moderate ability, and CEA, CA125, and CA724 have a low ability to predict A-cMNs. The combination of STM testing could improve SE in predicting A-cMNs.

Outcomes and safety of double-balloon enteroscopy in small bowel diseases: a single-center experience of 1531 procedures.

BACKGROUND: Double-balloon enteroscopy (DBE) has become a routine procedure in clinical practice for evaluation of small bowel diseases (SBDs). This study aimed to evaluate the diagnostic and therapeutic value of DBE in patients with suspected SBDs according to the patients' age and indications for the procedure. METHODS: The data of patients who underwent DBE at the endoscopy center of Changhai hospital between July 2013 and June 2018 were retrospectively reviewed. All features including demographic characteristics, indications, endoscopic findings, interventions and complications were collected. RESULTS: A total of 1291 consecutive patients who underwent 1531 DBE procedures (1375 diagnostic and 156 therapeutic) were included. The total diagnostic yield of DBE in cases of suspected SBDs was 58.9% (761/1291). The most common SBDs were Crohn's disease (CD) followed by tumors. The detection rates of CD and tumors by DBE were 18.3% (236/1291) and 12.7% (164/1291), respectively. The most frequent site of CD was the ileum (199/236, 84.3%), while that of tumors was the proximal small bowel (duodenum and jejunum, 115/164, 70.1%). In the young group (< 45 years), the majority of patients had CD, whereas tumors were the most common disease in the older group (≥ 45 years). The diagnostic yields for occult gastrointestinal bleeding (OGIB) and abdominal pain were 57.3% and 52.4%, respectively. In patients with OGIB, the detection rate of tumor was higher, whereas that of CD was higher in patients with abdominal pain. Polypectomy and foreign body removal were the predominant endoscopic interventions. DBE-associated complications were reported for 14 procedures (0.9%), including 3 diagnostic procedures (0.2%) and 11 therapeutic procedures (7.1%). CONCLUSION: DBE is a useful diagnostic tool for the investigation of SBDs, especially for CD and small bowel tumors. DBE is also a safe therapeutic procedure for polypectomy and foreign body removal.

Automated polyp segmentation for colonoscopy images: A method based on convolutional neural networks and ensemble learning.

PURPOSE: To automatically and efficiently segment the lesion area of the colonoscopy polyp image, a polyp segmentation method has been presented. METHODS: An ensemble model of pretrained convolutional neural networks was proposed, using Unet-VGG, SegNet-VGG, and PSPNet. Firstly, the Unet-VGG is obtained by the first 10 layers of VGG16 as the contraction path of the left half of the Unet. Then, the SegNet-VGG is acquired by fine-tuned transfer learning VGG16, using the first 13 layers of VGG16 as the encoder of the SegNet and combined the original decoder of the SegNet. By adjusting the input size of the Unet-VGG, SegNet-VGG, and PSPNet, the preprocessed data can be correctly fed to the three network models. The three models are used as the basic trainer to train and segment the datasets. Based on the ensemble learning algorithm, the weight voting method is used to ensemble the segmentation results corresponding to single basic trainer. RESULTS: Both IoU and DICE similarity score were used to evaluate the segmentation quality for cvc300 with 300 images, CVC-ClinicDB with 612 images, and ETIS-LaribPolypDB with 196 images. From the experimental results, the IoU and DICE obtained by the proposed method for the cvc300 datasets can reach up to 96.16% and 98.04%, respectively, the IoU and DICE for the CVC-ClinicDB datasets can reach up to 96.66% and 98.30%, respectively, whereas the IoU and DICE for the ETIS-LaribPolypDB datasets can reach up to 96.95% and 98.45%, respectively. Evaluation of the IoU and DICE in our methods shows higher accuracy than previous methods. CONCLUSIONS: The experimental results show that the proposed method improved correspondingly in IoU and DICE compared to a single basic trainer. The range of improvement is 1.98%-6.38%. The proposed ensemble learning succeeds in automatic polyp segmentation, which potentially helps to establish more polyp datasets.

The value of DNA image cytometry combined with brush routine cytology in diagnosing indeterminate biliary strictures: A large sample size retrospective study.

BACKGROUND AND AIM: Brush cytology is widely applied to diagnosis indeterminate biliary stricture but suffer from low sensitivity. Changes in DNA content are a character of malignant cell and can be detected by DNA image cytometry (DNA-ICM). The study aimed to estimate the value of routine cytology (RC), DNA-ICM, and their combination in diagnosing indeterminate biliary strictures. METHODS: A total of 362 patients who underwent both RC and DNA-ICM tests were analysed. Their results were retrospectively applied to final diagnoses. Diagnostic values were compared among RC, DNA-ICM, and their combination based on the location of strictures. RESULTS: The DNA-ICM and combination of two methods had higher diagnostic accuracy than RC in all strictures (63.3% vs 42.3%, P < 0.001, 64.36% vs 42.3%, P < 0.001) and in distal strictures (65.36% vs 42.81%, P < 0.001, 66.01% vs 42.81%, P < 0.001). But in proximal strictures, DNA-ICM showed no superior (51.8% vs 42.81%, P = 0.184). Combination of two methods was not fully significant superior to RC in proximal strictures (55.36% vs 39.29%, P = 0.089). After classification of "suspicious for malignancy" as positive for malignancy, the diagnostic accuracy of DNA-ICM was still higher than that of RC in all strictures (63.3% vs 51.9%, P = 0.002) and in distal strictures (65.36% vs 52.29%, P = 0.001). Combination of two methods was no superior to DNA-ICM alone (64.36% vs 63.3%, P = 0.757). The utilization of DNA-ICM was more accurate in distal strictures than in proximal strictures (65.36% vs 51.8%, P = 0.017). CONCLUSION: DNA-ICM is an objective and effective addition tool with RC, especially in distal strictures. The combination of DNA-ICM and RC showed no superior to DNA-ICM alone but could improve diagnostic accuracy to RC in proximal strictures although not fully significant.

22-Gauge biopsy needles have a better histological diagnostic yield in the discrimination of specific pancreatic solid neoplasms.

BACKGROUND: To overcome the limitations of using cytological specimen alone for the diagnosis of challenging pancreatic lesions, biopsy needles have been developed to procure histological specimens during EUS, especially for the discrimination of several specific pancreatic tumors requiring adequate histological samples. The aim of this study was to compare the diagnostic yield of EUS-guided 22-gauge (G) fine needle aspiration (FNA) needles and 22G fine needle biopsy (FNB) needles for sampling pancreatic masses. METHODS: We conducted a retrospective study of all EUS-guided sampling performed between November 2012 and April 2016. 422 cases sampled with a 22G FNA needle (N = 254) or a 22G FNB needle (N = 168) were recruited for this study. The specimen quality analyses, technical characteristics, accuracy, sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) for the pancreatic masses were reviewed and compared. RESULTS: There was no significant difference in the procurement of adequate histological specimens (75.0% vs. 79.5%; p = .277) or the presence of diagnostic histological specimens (71.3% vs. 77.4%; p = .155) between FNA and FNB groups, respectively. There were also no significant differences in the accuracy, sensitivity, specificity, PPVs, or NPVs of the cytological, histological, and overall analyses for FNA and FNB groups in the diagnosis of pancreatic malignancy. However, 22G biopsy needles demonstrated a better histological diagnostic yield in the discrimination of pancreatic adenocarcinoma and non-adenocarcinoma pancreatic neoplasms than 22G FNA needles (69.8% vs. 57.9%, p = .033). CONCLUSIONS: 22G FNB needle demonstrated a better histological diagnostic yield in the differentiation between pancreatic adenocarcinoma and non-adenocarcinoma pancreatic neoplasms.

A novel self-expanding biflanged metal stent vs tubular metal stent for EUS-guided transmural drainage of pancreatic pseudocyst: A retrospective, cohort study.

Although endoscopic ultrasound (EUS)-guided transmural drainage of pancreatic fluid collections with metal stents is generally preferred over plastic stents, its superiority among different types of metal stents has not yet been well studied. We conducted this study to compare clinical outcomes and complications of a novel self-expanding biflanged metal stent (BFMS) and a traditional-shaped tubular metal stent (TMS) in treating pancreatic pseudocyst (PPC).This was a retrospective analysis on consecutive patients with PPC underwent EUS-guided transmural drainage with either TMS or BFMS in a single tertiary center with expertise in management of complex biliary and pancreatic problems. The technical and functional success rate, reintervention, complications, and recurrence rate were evaluated.From September 2013 to January 2018, 125 patients (66.4% male, median age 47 years) underwent EUS-guided transmural drainage for PPC. Among them, 49 used TMS and 76 used BFMS. All patients met the inclusion criteria that cyst diameter was >6 cm or the distance between cyst and stomach wall was shorter than 1 cm. There was no difference in technical success (98% vs 97.4%, P = 1.0) or functional success rate (87.8% vs 92.1%, P = .54) using 2 types of metal stents. However, more procedure related complications occurred in TMS than in BFMS group. TMS group had a much higher migration rate than BFMS group (14.6% vs 0, P = .001), even though there was no significant difference in bleeding, infection, or death rate between 2 groups. With similar clinical outcomes, TMS group required more additional plastic stent placement than BFMS group for better drainage.TMS and BFMS placement can both be considered as methods of endoscopic transmural PPC drainage with equal efficacy, whereas BFMS could be preferred for fewer complications or less need of additional plastic stent placement.

Proteasome activator subunit 3 promotes pancreatic cancer growth via c-Myc-glycolysis signaling axis.

Pancreatic cancer has the worst prognosis among all cancers and novel markers and therapeutic targets are desperately needed for this terribly deadly disease. Proteasome activator subunit 3 (PSME3) is highly involved in the initiation and progression of many human cancers. However, the potential effect of PSME3 on pancreatic cancer remains largely unknown. In the present study, we first found that PSME3 was significantly upregulated in pancreatic cancer cells and tissues at both mRNA and protein levels using qRT-PCR, western blot analysis, Oncomine data mining and immunohistochemical analysis. High PSME3 expression was positively correlated with tumor size and pM stage, and was significantly correlated with poor prognosis in pancreatic cancer patients revealed by Kaplan-Meier analysis. Gene set enrichment analysis demonstrated that the gene sets related to cell proliferation and metastasis were positively correlated with elevated PSME3 expression. Consistently, silencing of PSME3 suppressed cell proliferation and invasive capacity of pancreatic cancer. Mechanistically, PSME3 inhibited the degradation of c-Myc and thus enhanced glycolysis, which ultimately led to the oncogenic effects of PSME3 on pancreatic cancer. Collectively, our data suggest that PSME3 plays oncogenic roles in pancreatic cancer by inhibiting c-Myc degradation to promote glycolysis, and could serve as a novel therapeutic target for pancreatic cancer treatment.

Captopril pretreatment protects the lung against severe acute pancreatitis induced injury via inhibiting angiotensin II production and suppressing Rho/ROCK pathway.

Acute pancreatitis (AP) usually causes acute lung injury, which is also known as acute pancreatitis associated lung injury (APALI). This study aimed to investigate whether captopril pretreatment was able to protect lung against APALI via inhibiting angiotensin II (Ang II) production and suppressing Rho/ROCK (Rho kinase) pathway in rats. Severe AP (SAP) was introduced to rats by bile-pancreatic duct retrograde injection of 5% sodium taurocholate. Rats were randomly divided into three groups. In the sham group, sham operation was performed; in the SAP group, SAP was introduced; in the pre-cpl + SAP group, rats were intragastrically injected with 5 mg/kg captopril 1 hour prior to SAP induction. Pathological examination of the lung and pancreas, evaluation of pulmonary vascular permeability by wet/dry ratio and Evans Blue staining, detection of serum amylase, Western blot assay for Ang II receptor type 1 (AT1), RhoA, ROCK (Rho kinase), and MLCK (myosin light chain kinase) were performed after the animals were sacrificed at 24 hours. After the surgery, characteristic findings of pancreatitis were observed, accompanied by lung injury. The serum amylase, Ang II, and lung expression of AT1, RhoA, ROCK, and MLCK increased dramatically in SAP rats. However, captopril pretreatment improved the histological changes, reduced the pathological score of the pancreas and lung, inhibited serum amylase and Ang II production, and decreased expression of AT1, RhoA, ROCK, and MLCK in the lung. These findings suggest that captopril pretreatment is able to protect the lung against APALI, which is, at least partially, related to the inhibition of Ang II production and the suppression of the Rho/ROCK pathway.

Adenovirus vector-mediated Gli1 siRNA induces growth inhibition and apoptosis in human pancreatic cancer with Smo-dependent or Smo-independent Hh pathway activation in vitro and in vivo.

Activation of Hedgehog (Hh) signaling pathway is a core molecular mechanism in pancreatic carcinogenesis. However, the inhibition of upstream Hh signals does not inhibit the growth of a subset of pancreatic cancer (PC). This study was to examine the effect of siRNA targeting Gli1, the downstream component of Hh pathway, on PC cells and to provide some insight into the underlying mechanisms. A Gli1siRNA-expressing adenovirus (Ad-U6-Gli1siRNA) was constructed, and its effect on PC cells was investigated in vitro and in vivo. Gli1 was expressed in 83.3% (20/24) PC tissues, whereas no expression was found in normal pancreatic ductal epithelium. Gli1 was expressed in SW1990 and CFPAC cells in which Smo was completely absent, as well as in PaTu8988, Panc-1 and BxPC-3 cells in which Smo was concomitantly present. Ad-U6-Gli1siRNA induced cell growth inhibition, strong G0/G1 cell cycle arrest and apoptosis in all five human PC cell lines. Meanwhile, Ad-U6-Gli1siRNA significantly suppressed the expression of Gli1, Ptch1 and two target genes, Cyclin D2 and Bcl-2, in all five lines. Furthermore, two tumor xenograft nude mice models were established by subcutaneously injecting Smo-positive Panc-1 cells or Smo-negative SW1990 cells. The in vivo experimental results demonstrated that Ad-U6-Gli1siRNA inhibited the growth of both Panc1-derived and SW1990-derived tumors and induced cell apoptosis. Our study indicates that Gli1-targeting siRNA could induce growth inhibition and apoptosis in PC through knockdown of Gli1 and its target genes; and this method may represent a more effective therapeutic strategy for PC with Smo-dependent or Smo-independent Hh pathway activation.

[Application of endoscopic ultrasonography in the diagnosis and management of gastrointestinal cancers].

Since its initial introduction in clinical practice, endoscopic ultrasonography(EUS) has been considered as a valuable tool for the diagnosis and staging of gastrointestinal cancers. With the improvement of equipments in the past decade, EUS-guided fine needle aspiration (EUS-FNA) techniques has been greatly developed, which opens a new avenue to therapeutic EUS. At present, endoscopic ultrasonography (EUS) has been widely applied in the clinical practice of the diagnosis and management of gastrointestinal cancers. In this paper, we summarize the latest data of the applications of EUS in the diagnosis and management of gastrointestinal cancers.

[mRNA expression of GLI1 in pancreatic carcinoma and clinical significance thereof].

OBJECTIVE: To investigate the mRNA expression of GLI1, a transcription regulator of Hedgehog signaling pathway, in human pancreatic carcinoma and to explore its clinical significance. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GLI1 in the tumor tissues, tissues near tumor, and normal tissues obtained during operation from 25 pancreatic carcinoma patients. RESULTS: The GLI1 mRNA expression rate of the tumor tissues was 68.0% (17/25), significantly higher than those of the tissues near tumor, and normal tissues [24.0% (6/25) and 0 (0/25) respectively, both P < 0.01]. The GLI1 mRNA expression rate was significantly associated with the differentiation degree of tumor tissue (P = 0.014), and not significantly associated with the tumor size, invasion, and metastasis (all P > 0.05). CONCLUSION: GLI1 mRNA expression is strong in pancreatic carcinoma tissues and is significantly associated with the differentiation degree of tumor tissue. With diagnostic implication, GLI1 mRNA expression may be regarded as a parameter of determining the degree of malignancy and prognosis of pancreatic carcinoma.