- Integration of the analysis of genetic markers with endoscopic ultrasound-guided fine-needle aspiration and cytologic evaluation has increased the accuracy of the preoperative diagnosis of ...pancreatic lesions. The application of high-throughput gene panel analysis using next-generation sequencing platforms is now offering a great opportunity for further improvements.
- To review the application of next-generation sequencing to the preoperative diagnosis of pancreatic lesions.
- For data acquisition, a PubMed search using the terms next-generation sequencing, pancreas, pancreatic lesions, pancreatic tumors, and EUS-FNA was performed covering the years 2000-2017.
- KRAS remains the gene most widely studied for preoperative single-gene tests. Next-generation sequencing reliably allows analysis of multiple gene markers starting from limited amounts of DNA. The study of multigene panels has become a very attractive option for the management and preoperative risk stratification of patients with pancreatic cancer.
AIM: To summarize the current knowledge about the potential relationship between hepatitis C virus(HCV) infection and the risk of several extra-liver cancers. METHODS: We performed a systematic ...review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis(PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews:(1) HCV and haematopoietic malignancies;(2) HCV and cholangiocarcinoma;(3) HCV and pancreatic cancer;(4) HCV and breast cancer;(5) HCV and kidney cancer;(6) HCV and skin or oral cancer; and(7) HCV and thyroid cancer. RESULTS: According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with:(1) a higher incidence of some B-cell Non-HodgkinLymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%;(2) an increased risk of intra-hepatic cholangiocarcinoma; and(3) a correlation between HCV prevalence and pancreatic cancer(PAC) incidence. CONCLUSION: To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are requiredto confirm or deny this association.
MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis b- and c-related-hepatocellularcarcinoma Sirio Fiorino Maria Letizia Bacchi-Reggiani Michela Visani Giorgia Acquaviva Adele Fornelli Michele Masetti Andrea Tura Fabio Grizzi Matteo Zanello Laura Mastrangelo Raffaele Lombardi Luca Di Tommaso Arrigo Bondi Sergio Sabbatani Andrea Domanico Carlo Fabbri Paolo Leandri Annalisa Pession Elio Jovine Dario de Biase
世界胃肠病学杂志：英文版,
04/2016
15
Journal Article
Aim of the present review is to summarize the current knowledge about the potential relationship between mi RNAs and hepatitis B virus(HBV)-hepatitis C virus(HCV) related liver diseases. A systematic ...computerbased search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine mi RNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma(HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: "HBV", "HCV", "hepatocellular carcinoma", "micro RNAs", "mi RNAs", "diagnosis", "prognosis", "therapy", "treatment". Some serum/plasma mi RNAs, including mi R-21, mi R-122, mi-125a/b, mi R-199a/b, mi R-221, mi R-222, mi R-223, mi R-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of mi RNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of mi RNAs for HCC early detection and prognosis.
In 2013 Guidelines on diagnosis and management of ASBO have been revised and updated by the WSES Working Group on ASBO to develop current evidence-based algorithms and focus indications and safety of ...conservative treatment, timing of surgery and indications for laparoscopy.
In absence of signs of strangulation and history of persistent vomiting or combined CT-scan signs (free fluid, mesenteric edema, small-bowel feces sign, devascularization) patients with partial ASBO can be managed safely with NOM and tube decompression should be attempted. These patients are good candidates for Water-Soluble-Contrast-Medium (WSCM) with both diagnostic and therapeutic purposes. The radiologic appearance of WSCM in the colon within 24 hours from administration predicts resolution. WSCM maybe administered either orally or via NGT both immediately at admission or after failed conservative treatment for 48 hours. The use of WSCM is safe and reduces need for surgery, time to resolution and hospital stay.NOM, in absence of signs of strangulation or peritonitis, can be prolonged up to 72 hours. After 72 hours of NOM without resolution, surgery is recommended.Patients treated non-operatively have shorter hospital stay, but higher recurrence rate and shorter time to re-admission, although the risk of new surgically treated episodes of ASBO is unchanged. Risk factors for recurrences are age <40 years and matted adhesions. WSCM does not decrease recurrence rates or recurrences needing surgery.Open surgery is often used for strangulating ASBO as well as after failed conservative management. In selected patients and with appropriate skills, laparoscopic approach is advisable using open access technique. Access in left upper quadrant or left flank is the safest and only completely obstructing adhesions should be identified and lysed with cold scissors. Laparoscopic adhesiolysis should be attempted preferably if first episode of SBO and/or anticipated single band. A low threshold for open conversion should be maintained.Peritoneal adhesions should be prevented. Hyaluronic acid-carboxycellulose membrane and icodextrin decrease incidence of adhesions. Icodextrin may reduce the risk of re-obstruction. HA cannot reduce need of surgery.Adhesions quantification and scoring maybe useful for achieving standardized assessment of adhesions severity and for further research in diagnosis and treatment of ASBO.
Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor ...resection.
The primary goal was to investigate alterations in KRAS, TP53, SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery.
Tumors from 15 patients with PDAC that survived more than 55 months after surgery ("LS") were analyzed for KRAS, TP53, IDH1, NRAS and BRAF using next-generation sequencing. SMAD4 and CDKN2A/p16 was tested using immunohistochemistry. MGMT promoter methylation was investigated.
Tumors from "LS" have a lower prevalence of KRAS and TP53 mutations and had more frequently SMAD4 retained expression, if compared with that of patients died within 24 months from surgery. The survival of patients with wild-type KRAS and TP53 tumors was more than twice longer than that of patients bearing KRAS and TP53 mutations (90.2 vs. 41.1 months). Patients with KRAS wild-type tumors and that retained SMAD4 expression had a survival twice longer than cases with alterations in both genes (83.8 vs. 36.7 months). Eleven tumors (39.3%) showed MGMT methylation.
Our data indicate that absence of KRAS, TP53 and SMAD4 genetic alterations may identify a subset of pancreatic carcinomas with better outcome.
Abstract
Background and study aims To assess the outcomes of urgent endoscopic retrograde cholangiopancreatography (ERCP) performed with a single-use duodenoscope (SUD) in patients with ...moderate-to-severe cholangitis.
Patients and methods Between 2021 and 2022 consecutive patients with moderate-to-severe cholangitis were prospectively enrolled to undergo urgent ERCP with SUD. Technical success was defined as the completion of the planned procedure with SUD. Multivariate analysis was used to identify factors related to incidence of adverse events (AEs) and mortality.
Results Thirty-five consecutive patients (15 female, age 81.4±6.7 years) were enrolled. Twelve (34.3%) had severe cholangitis; 26 (74.3%) had an American Society of Anesthesiologists (ASA) score ≥3. Twenty-eight patients (80.0%) had a naïve papilla. Biliary sphincterotomy and complete stone clearance were performed in 29 (82.9%) and 30 patients (85.7%), respectively; in three cases (8.6%), concomitant endoscopic ultrasound-gallbladder drainage was performed. Technical and clinical success rates were 100%. Thirty-day and 3-month mortality were 2.9% and 14.3%, respectively. One patient had mild post-ERCP pancreatitis and two had delayed bleeding. No patient or procedural variables were related to AEs. ASA score 4 and leucopenia were related to 3-month mortality; on multivariate analysis, leukopenia was the only variable independently related to 3-month mortality (odds ratio 12.8; 95% confidence interval 1.03–157.2; P=0.03).
Conclusions The results of this “proof of concept” study suggest that SUD use could be considered safe and effective for urgent ERCP for acute cholangitis. This approach abolishes duodenoscope contamination from infected patients without impairing clinical outcomes.
Borderline resectable pancreatic cancer may require extended resections in order to achieve tumor-free margins, especially in the case of up-front resections, but it is important to know the limits ...of surgical therapy in this disease. This study aimed to investigate the impact of extent of pancreatic and venous resection on short- and long-term outcomes in patients with pancreatic adenocarcinoma (PDAC).
This was a retrospective study from a prospectively maintained database of pancreatic resections for PDAC. Short- and long-term outcomes were analyzed in patients having borderline resectable PDAC submitted to up-front total pancreatectomy (TP) or pancreaticoduodenectomy (PD) with simultaneous portal vein (PV) and/or superior mesenteric vein (SMV) resection. Venous resections were carried out as tangential venous resection (TVR) or segmental venous resection (SVR). Patients were divided into 4 groups: (1) PD + TVR, (2) PD + SVR, (3) TP + TVR, (4) TP + SVR. Uni- and multivariate Cox regression analysis were performed to identify factors associated with survival.
Ninety-nine patients were submitted to simultaneous pancreatic and venous resection for PDAC. Among them, 25 were submitted to PD + TVR (25.3%), 12 to PD + SVR (12.1%), 23 to TP + TVR (23.2%), and 39 to TP + SVR (39.4%). Overall, major morbidity (Clavien-Dindo grade ≥ IIIA) was 26.3%. Thirty- and 90-day mortality were 3% and 11.1%, respectively. There were no significant differences among groups in terms of short-term outcomes. Median overall survival of patients submitted to PD + TVR was significantly higher than those to TP+SVR (29.5 vs 7.9 months, P = 0.001). Multivariate analysis identified TP (HR = 2.11; 95% CI: 1.31–3.44; P = 0.002) and SVR (HR = 2.01; 95% CI: 1.27–3.15; P = 0.003) as the only independent prognostic factors for overall survival.
Up-front TP associated to SVR was predictive of worse survival in borderline resectable PDAC. Perioperative treatments in high-risk surgical groups may improve such poor outcomes.
A hallmark of pancreatic ductal adenocarcinoma is the desmoplastic reaction, but its impact on the tumor behavior remains controversial. Our aim was to introduce a computer -aided method to precisely ...quantify the amount of pancreatic collagenic extra-cellular matrix, its spatial distribution pattern, and the degradation process.
A series of normal, inflammatory and neoplastic pancreatic ductal adenocarcinoma formalin-fixed and paraffin-embedded Sirius red stained sections were automatically digitized and analyzed using a computer-aided method.
We found a progressive increase of pancreatic collagenic extra-cellular matrix from normal to the inflammatory and pancreatic ductal adenocarcinoma. The two-dimensional fractal dimension showed a significant difference in the collagenic extra-cellular matrix spatial complexity between normal versus inflammatory and pancreatic ductal adenocarcinoma. A significant difference when comparing the number of cycles necessary to degrade the pancreatic collagenic extra-cellular matrix in normal versus inflammatory and pancreatic ductal adenocarcinoma was also found. The difference between inflammatory and pancreatic ductal adenocarcinoma was also significant. Furthermore, the mean velocity of collagenic extra-cellular matrix degradation was found to be faster in inflammatory and pancreatic ductal adenocarcinoma than in normal.
These findings demonstrate that inflammatory and pancreatic ductal adenocarcinomas are characterized by an increased amount of pancreatic collagenic extra-cellular matrix and by changes in their spatial complexity and degradation. Our study defines new features about the pancreatic collagenic extra-cellular matrix, and represents a basis for further investigations into the clinical behavior of pancreatic ductal adenocarcinoma and the development of therapeutic strategies.
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