The changes perhaps reflect standardization and consolidation of diagnostic tests for pancreatic cancer in the Western world and further in-depth analysis would be required.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers largely due to disseminated disease at the time of presentation. Here, we investigated the role and mechanism of action of the metastasis-associated protein anterior gradient 2 (AGR2) in the pathogenesis of pancreatic cancer. AGR2 was induced in all sporadic and familial pancreatic intraepithelial precursor lesions (PanIN), PDACs, circulating tumor cells, and metastases studied. Confocal microscopy and flow cytometric analyses indicated that AGR2 localized to the endoplasmic reticulum (ER) and the external surface of tumor cells. Furthermore, induction of AGR2 in tumor cells regulated the expression of several ER chaperones (PDI, CALU, RCN1), proteins of the ubiquitin-proteasome degradation pathway (HIP2, PSMB2, PSMA3, PSMC3, and PSMB4), and lysosomal proteases [cathepsin B (CTSB) and cathepsin D (CTSD)], in addition to promoting the secretion of the precursor form pro-CTSD. Importantly, the invasiveness of pancreatic cancer cells was proportional to the level of AGR2 expression. Functional downstream targets of the proinvasive activity of AGR2 included CTSB and CTSD in vitro, and AGR2, CTSB, and CTSD were essential for the dissemination of pancreatic cancer cells in vivo. Taken together, the results suggest that AGR2 promotes dissemination of pancreatic cancer and that its cell surface targeting may permit new strategies for early detection as well as therapeutic management.
Background Enhanced recovery after surgery (ERAS) protocols are evidence-based, multimodal and patient-centred approach to optimize patient care and experience during their perioperative pathway. It has been shown to be effective in reducing length of hospital stay and improving clinical outcomes. However, evidence on its effective in liver surgery remains weak. The aim of this review is to investigate clinical benefits, cost-effectiveness and compliance to ERAS protocols in liver surgery. Methods A systematic literature search was conducted using CINAHL Plus, EMBASE, MEDLINE, PubMed and Cochrane for randomized control trials (RCTs) and cohort studies published between 2008 and 2019, comparing effect of ERAS protocols and standard care on hospital cost, LOS, complications, readmission, mortality and compliance. Results The search resulted in 6 RCTs and 21 cohort studies of 3739 patients (1777 in ERAS and 1962 in standard care group). LOS was reduced by 2.22 days in ERAS group (MD = −2.22; CI, −2.77 to −1.68; p < 0.00001) compared to the standard care group. Fewer patients in ERAS group experienced complications (RR, 0.71; 95% CI, 0.65-0.77; p = < 0.00001). Hospital cost was significantly lower in the ERAS group (SMD = −0.98; CI, −1.37 to-0.58; p < 0.0001). Conclusion Our review concluded that the introduction of ERAS protocols is safe and feasible in hepatectomies, without increasing mortality and readmission rates, whilst reducing LOS and risk of complications, and with a significant hospital cost savings. Laparoscopic approach may be necessary to reduce complication rates in liver surgery. However, further studies are needed to investigate overall compliance to ERAS protocols and its impact on clinical outcomes.
IntroductionRetained sponges and instruments (RSI) due to surgery are a recognised medical ‘never event’ and have catastrophic implications for patients, healthcare professionals and medical care providers. The aim of this review was to elucidate the extent of the problem of RSI and to identify preventative strategies.MethodsA comprehensive literature search was performed on MEDLINE®, Embase™, the Science Citation Index and Google™ Scholar for articles published in English between January 2000 and June 2012. Studies outlining the incidence, risk, management and attempts to prevent RSI following surgical intervention were retrieved.ResultsThe overall incidence of RSI is low although its incidence is substantially higher in operations performed on open cavities. Sponges are the most commonly retained item when compared with needles and instruments. Clinical presentation is varied, leading to avoidable morbidity, and the error is indefensible medicolegally. Risk factors include emergency operations, operations involving unexpected change in procedure, raised body mass index, and a failure to perform accurate sponge and instrument counts. The existing strategy for prevention is manual counting of sponges and instruments undertaken by surgical personnel. This, however, is fallible. Computer assisted counting of sponges using barcodes and gauze sponges tagged with a radiofrequency identification device aiding manual counting have been trialled recently, with success.ConclusionsVigilance among operating theatre personnel is paramount if RSI is to be prevented. Prospective multicentre trials to assess efficacy of new technologies aiding manual counting should be undertaken if this medical error is to be eliminated completely.
Background: Pancreatic cancer is the 5th leading cause of cancer death in both males and females. In recent years, a wealth of gene and protein expression studies have been published broadening our understanding of pancreatic cancer biology. Due to the explosive growth in publicly available data from multiple different sources it is becoming increasingly difficult for individual researchers to integrate these into their current research programmes. The Pancreatic Expression database, a generic web-based system, is aiming to close this gap by providing the research community with an open access tool, not only to mine currently available pancreatic cancer data sets but also to include their own data in the database.
Overall, there was a decline in ASR(W) for gallbladder cancer. Better diagnostic modalities resulting in appropriate staging of gallbladder/biliary cancers, as well as changes in the ICD classification and perhaps increased awareness, may have contributed to these trends.
Pancreatic ductal adenocarcinoma (PDAC) accounts for over 213 000 deaths worldwide each year, largely due to late diagnosis. One of the risk factors for the development of PDAC is chronic pancreatitis (CP); the intense desmoplastic reaction makes differentiation between the two conditions extremely difficult. In order to identify biomarkers for noninvasive diagnosis, we performed 2-D DIGE analysis of urine samples from healthy individuals and patients with PDAC and CP. Despite considerable intersample heterogeneity, a total of 127 statistically valid (p<0.05), differentially expressed protein spots were detected, 101 of which were identified using MALDI-TOF MS. A number of these, including annexin A2, gelsolin and CD59 have already been associated with PDAC, however, their validation using immunoblotting proved challenging. This is probably due to extensive PTMs and processing thus indicating the need for raising specific antibodies for urinary proteins. Despite this, our study clearly demonstrates that urine is a valid source of noninvasive biomarkers in patients with pancreatic diseases.
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