Search

Background: Solid pseudopapillary neoplasm (SPN) is an uncommon pathology of the pancreas with unpredictable malignant potential. Endoscopic ultrasound (EUS) assessment plays a vital role in lesion characterization and confirmation of the tissue diagnosis. However, there is a paucity of data regarding the imaging assessment of these lesions., Aim: To determine the characteristic EUS features of SPN and define its role in preoperative assessment., Methods: This was an international, multicenter, retrospective, observational study of prospective cohorts from 7 large hepatopancreaticobiliary centers. All cases with postoperative histology of SPN were included in the study. Data collected included clinical, biochemical, histological and EUS characteristics., Results: One hundred and six patients with the diagnosis of SPN were included. The mean age was 26 years (range 9 to 70 years), with female predominance (89.6%). The most frequent clinical presentation was abdominal pain (80/106; 75.5%). The mean diameter of the lesion was 53.7 mm (range 15 to 130 mm), with the slight predominant location in the head of the pancreas (44/106; 41.5%). The majority of lesions presented with solid imaging features (59/106; 55.7%) although 33.0% (35/106) had mixed solid/cystic characteristics and 11.3% (12/106) had cystic morphology. Calcification was observed in only 4 (3.8%) cases. Main pancreatic duct dilation was uncommon, evident in only 2 cases (1.9%), whilst common bile duct dilation was observed in 5 (11.3%) cases. One patient demonstrated a double duct sign at presentation. Elastography and Doppler evaluation demonstrated inconsistent appearances with no emergence of a predictable pattern. EUS guided biopsy was performed using three different types of needles: Fine needle aspiration (67/106; 63.2%), fine needle biopsy (37/106; 34.9%), and Sonar Trucut (2/106; 1.9%). The diagnosis was conclusive in 103 (97.2%) cases. Ninety-seven patients were treated surgically (91.5%) and the post-surgical SPN diagnosis was confirmed in all cases. During the 2-year follow-up period, no recurrence was observed., Conclusion: SPN presented primarily as a solid lesion on endosonographic assessment. The lesion tended to be located in the head or body of the pancreas. There was no consistent characteristic pattern apparent on either elastography or Doppler assessment. Similarly SPN did not frequently cause stricture of the pancreatic duct or common bile duct. Importantly, we confirmed that EUS-guided biopsy was an efficient and safe diagnostic tool. The needle type used does not appear to have a significant impact on the diagnostic yield. Overall SPN remains a challenging diagnosis based on EUS imaging with no pathognomonic features. EUS guided biopsy remains the gold standard in establishing the diagnosis., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Pancreatic cyst fluids (PCFs) enriched in tumor-derived DNA are a potential source of new biomarkers. The study aimed to analyze germinal variants and mutational profiles of cell-free (cf)DNA shed into the cavity of pancreatic cysts., Methods: The study cohort consisted of 71 patients who underwent endoscopic ultrasound fine-needle aspiration of PCF. Five malignant cysts, 19 intraductal papillary mucinous neoplasms (IPMNs), 11 mucinous cystic neoplasms (MCNs), eight serous cystic neoplasms (SCNs), and 28 pseudocysts were identified. The sequencing of 409 genes included in Comprehensive Cancer Panel was performed using Ion Proton System. The mutation rate of the KRAS and GNAS canonical loci was additionally determined using digital PCR., Results: The number of mutations detected with NGS varied from 0 to 22 per gene, and genes with the most mutations were: TP53, KRAS, PIK3CA, GNAS, ADGRA2, and APC. The frequencies of the majority of mutations did not differ between non-malignant cystic neoplasms and pseudocysts. NGS detected KRAS mutations in malignant cysts (60%), IPMNs (32%), MCNs (64%), SCNs (13%), and pseudocysts (14%), with GNAS mutations in 20%, 26%, 27%, 13%, and 21% of samples, respectively. Digital PCR-based testing increased KRAS (68%) and GNAS (52%) mutations detection level in IPMNs, but not other cyst types., Conclusions: We demonstrate relatively high rates of somatic mutations of cancer-related genes, including KRAS and GNAS, in cfDNA isolated from PCFs irrespectively of the pancreatic cyst type. Further studies on molecular mechanisms of pancreatic cysts malignant transformation in relation to their mutational profiles are required.

Intestinal transporters and metabolizing enzymes are the important factors of the intestinal absorption barrier. Because there is evidence that their expression and function may be affected during inflammatory conditions, we investigated gene expression, protein abundance, and regulation of relevant intestinal transporters and metabolizing enzymes in the intestinal mucosa of patients with ulcerative colitis (UC). Specimens from inflamed and noninflamed tissues of 10 patients with UC as well as colonic control tissues of 10 patients without inflammation were subjected to gene (9 enzymes, 15 transporters, 9 cytokines) and microRNA (N = 54) expression analysis. Protein abundance was quantified by liquid chromatography-tandem mass spectrometry-based targeted proteomics. Gene expression of several metabolizing enzymes (e.g., CYP2C9, UGT1A1) and transporters such as ABCB1 (ABCB1), ABCG2 (ABCG2), and monocarboxylate transporter 1 (MCT1, SLC16A1) were significantly decreased during inflammation and negatively correlated to microRNAs. On contrary, multidrug resistance-protein 4 (MRP4, ABCC4), organic anion-transporting polypeptide 2B1 (OATP2B1, SLCO2B1), and organic cation transporter-like 2 (ORCTL2, SLC22A18) were significantly elevated in inflamed tissue. However, at protein level, these findings could only be confirmed for MCT1. UC is associated with complex changes in the intestinal expression of enzymes, transporters, cytokines, and microRNAs, which may affect efficacy of anti-inflammatory drug therapy or the disease state itself., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Pancreatic cyst fluids (PCFs) enriched in tumour-derived proteins are considered a potential source of new biomarkers. This study aimed to determine compositional and quantitative differences between the degradome and proteome of PCFs aspirated from different types of pancreatic cyst lesions (PCLs). 91 patients who underwent endoscopic ultrasound-fine needle aspiration under routine clinical diagnosis of PCLs were enrolled. Four cysts were malignant (CAs), and 87 were nonmalignant and consisted of 18 intraductal papillary mucinous neoplasms (IPMNs), 14 mucinous cystic neoplasms (MCNs), nine serous cystic neoplasms (SCNs), 29 pseudocysts (PCs), and 17 unclassified. Profiles of the <5 kDa fraction, the degradome, and the trypsin-digested proteome were analysed using an LTQ-Orbitrap Elite mass spectrometer coupled with a nanoACQUITY LC system. Qualitative analyses identified 796 and 366 proteins in degradome and proteome, respectively, and 689 (77%) and 285 (78%) of them were present in the Plasma Proteome Database. Gene Ontology analysis showed a significant overrepresentation of peptidases and peptidases inhibitors in both datasets. In the degradome fraction, quantitative values were obtained for 6996 peptides originating from 657 proteins. Of these, 2287 peptides were unique to a single type, and 515 peptides, derived from 126 proteins, were shared across cyst types. 32 peptides originating from 12 proteins had differential (adjusted p -value ≤0.05, FC ≥1.5) abundance in at least one of the five cysts types. In proteome, relative expression was measured for 330 proteins. Of them, 33 proteins had significantly (adjusted p -value ≤0.05, FC ≥1.5) altered abundance in at least one of the studied groups and 19 proteins appeared to be unique to a given cyst type. PCFs are dominated by blood proteins and proteolytic enzymes. Although differences in PCF peptide composition and abundance could aid classification of PCLs, the unpredictable inherent PCF proteolytic activity may limit the practical applications of PCF protein profiling.

Pathogenesis of primary sclerosing cholangitis (PSC) may involve impaired bile acid (BA) homeostasis. We analyzed expressions of factors mediating enterohepatic circulation of BA using ileal and colonic (ascending and sigmoid) biopsies obtained from patients with PSC with and without ulcerative colitis (UC) and explanted PSC livers. Two-fold increase of BA-activated farnesoid X receptor (FXR) protein levels were seen in ascending and sigmoid colon of PSC patients with correspondingly decreased apical sodium-dependent BA transporter (ASBT) gene expression. This was associated with increased OSTβ protein levels in each part of analyzed gut. An intestinal fibroblast growth factor (FGF19) protein expression was significantly enhanced in ascending colon. Despite increased hepatic nuclear receptors (FXR, CAR, SHP), and FGF19, neither CYP7A1 suppression nor CYP3A4 induction were observed. The lack of negative regulation of BA synthesis may be accountable for lower levels of cholesterol observed in PSC in comparison to primary biliary cholangitis (PBC). In conclusion, chronic cholestasis in PSC induces adaptive changes in expression of BA transporters and FXR in the intestine. However hepatic impairment of expected in chronic cholestasis downregulation of CYP7A1 and upregulation of CYP3A4 may promote BA-induced liver injury in PSC.

Background: Randomized trials have confirmed the efficacy of prucalopride for the treatment of chronic constipation up to 12 weeks. This study aimed to assess the efficacy of prucalopride over a 24-week period (ClinicalTrials.gov: NCT01424228)., Methods: Adults with chronic constipation and ≤2 spontaneous complete bowel movements (SCBMs)/week were randomized to receive prucalopride 2 mg or placebo daily for 24 weeks. The primary endpoint was the proportion of patients achieving a mean of ≥3 SCBMs/week over the treatment period, assessed using daily e-diaries. Secondary outcomes and safety parameters were assessed throughout the study., Key Results: Overall, 361 patients were randomized and received prucalopride or placebo. Baseline characteristics were similar in the prucalopride (N = 181) and placebo (N = 180) groups. Mean age was 48.9 years (standard deviation, 16.0) and most patients were women. The proportion of participants achieving the primary endpoint was not statistically different between the prucalopride and placebo groups (25.1% vs 20.7%; p = 0.367). There was also no statistically significant difference between groups over the first 12-week period (prucalopride, 25.1%; placebo, 20.1%; p = 0.341). There were no statistically significant differences between groups for most secondary endpoints. No new safety concerns were identified., Conclusions & Inferences: This trial did not show statistically significant improvements in primary or secondary outcomes with prucalopride compared with placebo over 24 or 12 weeks. This is in contrast to the results of four previous 12-week trials, which demonstrated prucalopride to be significantly more effective than placebo. An extensive evaluation did not provide an explanation for the null efficacy results of this study., (© 2015 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Anatomic variations of the right biliary system are one of the most common risk factors for sectoral bile duct injury (BDI) during cholecystectomy. Isolated right posterior BDI may in particular be a challenge for both diagnosis and management. Herein we describe two cases of isolated right posterior sectoral BDI that took place during laparoscopic cholecystectomy. Despite effective external biliary drainage from the liver hilum in both cases, there was a persistent biliary leak observed which was not visible on endoscopic retrograde cholangiogram. Careful evaluation of images from both endoscopic and magnetic resonance cholangiograms revealed the diagnosis of an isolated right posterior sectoral BDI. These were treated with a delayed bisegmental (segments 6 and 7) liver resection and a Roux-en-Y hepaticojejunostomy respectively with good outcomes at 24 and 4 mo of follow-up. This paper discusses strategies for prevention of such injuries along with the diagnostic and therapeutic challenges it offers.

Context: Fibrolamellar hepatocellular carcinoma is a rare liver tumor with the propensity to metastasize to the lymph nodes months or years after initial surgery. However, its metastatic spread to the pancreas was previously reported only in a child., Case Report: We present an unusual case of a young female patient who was repeatedly treated by surgical excision of abdominal and mediastinal lymph node recurrences between 2 and 6 years after left hepatic lobectomy for fibrolamellar hepatocellular carcinoma. At 8 years following her initial surgery, the patient was diagnosed with pancreatic head metastasis and a pancreaticoduodenectomy was performed. Postoperative course was uneventful and the patient did not experience recurrence within the last 18 months., Conclusion: The metastasis of fibrolamellar hepatocellular carcinoma to the pancreas is highly exceptional but possible and its excision appears warranted as well.

Background/aims: The aim of the study was to analyze in-hospital morbidity and mortality after pancreatoduodenectomy (PD) with a modified duct-to-mucosa pancreaticojejunostomy., Methodology: We retrospectively analyzed 101 consecutive patients who underwent PD at our center between January 2002 and December 2010. Two-layered duct-to-mucosa pancreaticojejunostomy was performed over an internal transanastomotic stent in all patients., Results: The overall in-hospital morbidity and mortality rate was 48% and 6%, respectively. Three patients died as a consequence of local complications including mesenteric ischemia in two and acute necrotizing pancreatitis in one case. Pancreatic fistula occurred in one (1%) patient and was treated conservatively with good outcome. The wound infection was the most common surgical complication (20/101; 20%) and occurred more often in patients who had a biliary stent inserted endoscopically prior to surgery (15/38; 39%), as compared to those without the stent (5/63; 8%; p=0.0003)., Conclusions: The results of the present study suggest that a two-layered duct-to-mucosa pancreaticojejunostomy with internal transanastomotic stent is a safe anastomosis, associated with a very low risk of pancreatic fistula. The presence of a biliary stent at the time of surgery represents a risk factor for the development of postoperative wound infection.

Background: Clinically significant primary biliary cirrhosis occurs in 2.5% of patients with systemic sclerosis. Primary biliary cirrhosis-specific autoantibodies include anti-mitochondrial, anti-glycoprotein 210, and anti-sp100 antibodies. The majority of asymptomatic anti-mitochondrial-positive subjects express histological features of primary biliary cirrhosis. Early detection of primary biliary cirrhosis is important, as timely introduction of ursodeoxycholic acid may improve prognosis. The aim was to assess the prevalence of MIT3 IgG-anti-mitochondrial, gp210, sp100 and other autoantibodies in patients with systemic sclerosis and compare the clinical and biochemical parameters in those who are primary biliary cirrhosis-specific autoantibodies positive and negative., Materials/methods: Fifty-two consecutive patients with systemic sclerosis were included. Thirty-three suffered from limited skin SS and 19 from diffuse SS., Results: Eight (15%) patients with systemic sclerosis tested positive for primary biliary cirrhosis-specific autoantibodies. No significant differences were observed between primary biliary cirrhosis-specific autoantibodies positive and negative subjects in terms of various demographic, clinical or biochemical features. A trend towards increased prevalence of chronic fatigue in primary biliary cirrhosis-specific autoantibodies positive patients was observed., Conclusions: Primary biliary cirrhosis-specific autoantibodies were detected in 15% of the systemic sclerosis patients. Since patients with primary biliary cirrhosis-specific antibodies are at high-risk or do suffer from primary biliary cirrhosis, screening for primary biliary cirrhosis-specific autoantibodies may be considered during routine assessment of systemic sclerosis.

Background: Endosonography (EUS), which merges endoscopic and ultrasound examinations, is a useful modality to display abnormal vessels that develop in the intrinsic circulation, frequently called "deep" varices. If these pathological veins exceed of 5 mm diameter, they significantly increase the risk of bleeding among patients with cirrhosis. In the most recent pilot study EUS proved useful to assess children for orthotopic liver transplantation (OLT)., Aim: We performed a cross-sectional study of EUS on 33 (22 males and 11 females) adult cirrhotic subjects being assessed for OLT., Materials/methods: We used an echoendoscope at 7.5 MHz/12 MHz/20 MHz to evaluate the esophagus and stomach, including "deep" periesophageal/perigastric varices (adjacent to the muscularis propria) and paraesophageal/paragastric varices (outside the muscularis propria). "Deep" varices were considered to be large if >5 mm., Results: On endoscopy, 26 (79%) patients showed esophageal varices (EV), including 11 (33%) with large (>5 mm) varices. Gastric varices (GV) were observed in 13 (39%) subjects, with 3 patients displaying large (>5 mm) varices. On EUS large "deep" EV (both para and periesophageal) were observed in 12 (36%) subjects, among whom 5 (42%) did not have large varices on endoscopy. Large "deep" GV were found on EUS in 12 (36%) subjects. On endoscopy 4 of them (33%) showed no varices and 3 (25%) had small GV., Conclusions: EUS offers a precise evaluation of portal hypertension in OLT candidates. "Deep" potentially dangerous varices, which are undetected with routine endoscopy, were noted in a significant proportion of patients. The role of EUS in prioritizing subjects for OLT must be evaluated in a prospective study.

Objective: To evaluate the role of 5T4 antigen in gastric cancer progression and prognosis., Design: A prospective study of 5T4 antigen expression in primary, secondary and recurrent gastric carcinoma, the relationship to selected prognostic parameters and the course of disease., Patients: Eighty six patients operated on for gastric cancer. TISSUE: One hundred and twenty two gastric tumours were studied, including 86 primary carcinomas, 32 coexisting lymph node metastases and four recurrent carcinomas., Methods: Immunohistochemistry using 5T4 monoclonal antibody on frozen sections., Results: The 5T4 antigen was detected in 41% of primary gastric tumours including early gastric cancer. A strong relationship was found between 5T4 positivity and tumour histology. Thus, 52% of gastric carcinomas of intestinal type expressed 5T4 antigen compared with 28% of the diffuse type (P = 0.028). Among 16 sets of primary gastric carcinomas and regional lymph node metastases, coordinate 5T4 expression was seen in 14 cases; the other two showed acquisition of positivity on metastatic tumour cells (carcinomas of diffuse type). 5T4 antigen was detected more frequently in carcinomas with p53 accumulation compared with those with undetectable p53 levels (P = 0.015). The presence of 5T4 in cancer cells was correlated with poor short-term prognosis (24% vs 49% of 2 year survival for 5T4 positive and negative tumours respectively, P = 0.024). The effect on survival was evident in the p53 negative group, with patients 5T4 positive showing worse survival (28% vs 60% in 2 years)., Conclusions: Our results suggest that the assessment of 5T4 expression in gastric carcinoma can be helpful in identifying patients with poor short-term prognosis.