Anesthetics and Long Term Cancer Outcomes: May Epigenetics Be the Key for Pancreatic Cancer?
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ABSTRACT:
SUBMITTER: Mokini Z
PROVIDER: S-EPMC9414834 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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Anesthetics and Long Term Cancer Outcomes: May Epigenetics Be the Key for Pancreatic Cancer?
Mokini Zhirajr Z Cama Alessandro A Forget Patrice P
Medicina (Kaunas, Lithuania) 20220814 8
Knowledge shows a divergence of results between preclinical and clinical studies regarding anesthesia and postoperative progression of cancer. While laboratory and animal data from then 2000s onwards raised much enthusiasm in this field of research leading to several clinical investigations worldwide, data from randomized trials seem to have killed off hope for many scientists. However several aspects of the actual knowledge should be reevaluated and there is space for new strategies of investig ...[more]
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Project description:ImportanceIntraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that can give rise to pancreatic cancer (PC). Limited population data exist on their prevalence, natural history, or risk of malignant transformation (IPMN-PC).ObjectiveTo fill knowledge gaps in epidemiology of IPMNs and associated PC risk by estimating population prevalence of IPMNs, associated PC risk, and proportion of IPMN-PC.Design, setting, and participants: This retrospective cohort study was conducted in Olmsted County, Minnesota. Using the Rochester Epidemiology Project (REP), patients aged 50 years and older with abdominal computed tomography (CT) scans between 2000 and 2015 were randomly selected (CT cohort). All patients from the REP with PC between 2000 and 2019 were also selected (PC cohort). Data were analyzed from November 2021 through August 2023.Main outcomes and measuresCIs for PC incidence estimates were calculated using exact methods with the Poisson distribution. Cox models were used to estimate age, sex, and stage-adjusted hazard ratios for time-to-event end points.ResultsThe CT cohort included 2114 patients (1140 females [53.9%]; mean [SD] age, 68.6 [12.1] years). IPMNs were identified in 231 patients (10.9%; 95% CI, 9.7%-12.3%), most of which were branch duct (210 branch-duct [90.9%], 16 main-duct [6.9%], and 5 mixed [2.2%] IPMNs). There were 5 Fukuoka high-risk (F-HR) IPMNs (2.2%), 39 worrisome (F-W) IPMNs (16.9%), and 187 negative (F-N) IPMNs (81.0%). After a median (IQR) follow-up of 12.0 (8.1-15.3) years, 4 patients developed PC (2 patients in F-HR and 2 patients in F-N groups). The PC incidence rate per 100 person years for F-HR IPMNs was 34.06 incidents (95% CI, 4.12-123.02 incidents) and not significantly different for patients with F-N IPMNs compared with patients without IPMNs (0.16 patients; 95% CI, 0.02-0.57 patients vs 0.11 patients; 95% CI, 0.06-0.17 patients; P = .62). The PC cohort included 320 patients (155 females [48.4%]; mean [SD] age, 72.0 [12.3] years), and 9.8% (95% CI, 7.0%-13.7%) had IPMN-PC. Compared with 284 patients with non-IPMN PC, 31 patients with IPMN-PC were older (mean [SD] age, 76.9 [9.2] vs 71.3 [12.5] years; P = .02) and more likely to undergo surgical resection (14 patients [45.2%] vs 60 patients [21.1%]; P = .003) and more-frequently had nonmetastatic PC at diagnosis (20 patients [64.5%] vs 130 patients [46.8%]; P = .047). Patients with IPMN-PC had better survival (adjusted hazard ratio, 0.62; 95% CI, 0.40-0.94; P = .03) than patients with non-IPMN PC.Conclusions and relevanceIn this study, CTs identified IPMNs in approximately 10% of patients aged 50 years or older. PC risk in patients with F-N IPMNs was low and not different compared with patients without IPMNs; approximately 10% of patients with PC had IPMN-PC, and they had better survival compared with patients with non-IPMN PC.
| S-EPMC10582793 | biostudies-literature
Project description:BackgroundThe short-term morbidity associated with post-operative pancreatic fistula (POPF) is well established, however data regarding the long-term impact are lacking. We aim to characterize long-term oncologic outcomes of POPF after pancreatic resection through a single institution, retrospective study of pancreatic resections performed for adenocarcinoma from 2009 to 2016.MethodsKaplan-Meier survival analysis, logistic regression, and multivariate analysis (MVA) were used to evaluate impact of POPF on overall survival (OS), disease free survival (DFS), and receipt of adjuvant chemotherapy (AC).Results767 patients were included. 82 (10.6%) developed grade B (n = 67) or C (n = 15) POPF. Grade C POPF resulted in decreased OS when compared to no POPF (20.22 vs 26.33 months, p = 0.027) and to grade B POPF (20.22 vs. 26.87 months, p = 0.049). POPF patients were less likely to receive AC than those without POPF (59.5% vs 74.9%, p = 0.003) and grade C POPF were less likely to receive AC than all others (26.7% vs 74.2%, p = 0.0001).ConclusionPOPF patients are less likely to receive AC and more likely to have delay in time to AC. These factors are exacerbated in grade C POPF and likely contribute to decreased OS. These findings validate the clinical significance of the ISGPF definition of POPF.
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Project description:BackgroundThe number of elderly patients with pancreatic cancer is growing, however clinical data on the short-term outcomes, rate of adjuvant chemotherapy, and survival in these patients are limited and we therefore performed a nationwide analysis.MethodsData from the prospective Dutch Pancreatic Cancer Audit were analyzed, including all patients undergoing pancreatic cancer resection between January 2014 and December 2016. Patients were classified into two age groups: <75 and ≥75 years. Major complications (Clavien-Dindo grade 3 or higher), 90-day mortality, rates of adjuvant chemotherapy, and survival were compared between age groups. Factors associated with start of adjuvant chemotherapy and survival were evaluated with logistic regression and multivariable Cox regression analysis.ResultsOf 836 patients, 198 were aged ≥75 years (24%) and 638 were aged <75 years (76%). Median follow-up was 38 months (interquartile range [IQR] 31-47). Major complications (31% vs. 28%; p = 0.43) and 90-day mortality (8% vs. 5%; p = 0.18) did not differ. Adjuvant chemotherapy was started in 37% of patients aged ≥75 years versus 69% of patients aged <75 years (p < 0.001). Median overall survival (OS) was 15 months (95% confidence interval [CI] 14-18) versus 21 months (95% CI 19-24; p < 0.001). Age ≥75 years was not independently associated with OS (hazard ratio 0.96, 95% CI 0.79-1.17; p = 0.71), but was associated with a lower rate of adjuvant chemotherapy (odds ratio 0.27, 95% CI 0.18-0.40; p < 0.001).ConclusionsThe rate of major complications and 90-day mortality after pancreatic resection did not differ between elderly and younger patients; however, elderly patients were less often treated with adjuvant chemotherapy and their OS was shorter.
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Project description:MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two relevant classes of non-coding RNAs (ncRNAs) that play a pivotal role in a number of molecular processes through different epigenetic regulatory mechanisms of gene expression. As a matter of fact, the altered expression of these types of RNAs leads to the development and progression of a varied range of multifactorial human diseases. Several recent reports elucidated that miRNA and lncRNAs have been implicated in pancreatic cancer (PC). For instance, dysregulation of such ncRNAs has been found to be associated with chemoresistance, apoptosis, autophagy, cell differentiation, tumor suppression, tumor growth, cancer cell proliferation, migration, and invasion in PC. Moreover, several aberrantly expressed miRNAs and lncRNAs have the potential to be used as biomarkers for accurate PC diagnosis. Additionally, miRNAs and lncRNAs are considered as promising clinical targets for PC. Therefore, in this review, we discuss recent experimental evidence regarding the clinical implications of miRNAs and lncRNAs in the pathophysiology of PC, their future potential, as well as the challenges that have arisen in this field of study in order to drive forward the design of ncRNA-based diagnostics and therapeutics for PC.
| S-EPMC9637816 | biostudies-literature
Project description:Acute normovolemic hemodilution (ANH) is a useful intraoperative blood conservation technique. However, the impact on long-term outcomes in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The present study investigated the impact of ANH on long-term outcomes in patients with PDAC undergoing radical surgery. Data from 155 resectable PDAC cases were collected. Patients were categorized according to whether or not they had received intraoperative allogeneic blood transfusion (ABT) or ANH. Postoperative complications, recurrence-free survival (RFS) and disease-specific survival (DSS), before and after propensity score matching (PSM), were compared among patients who did and did not receive ANH. A total of 44 patients (28.4%) were included in the ANH group and 30 patients (19.4%) were included in the ABT group; 81 (52.3%) patients, comprising the standard management (STD) group, received neither ANH nor ABT. The ABT group had the worst prognosis among them. Before PSM, ANH was significantly associated with decreased RFS (P=0.043) and DSS (P=0.029) compared with the STD group before applying Bonferroni correction; however, no significant difference was observed after applying Bonferroni correction. Cox regression analysis identified ANH as an independent prognostic factor for RFS [relative risk (RR), 1.696; P=0.019] and DSS (RR, 1.876; P=0.009). After PSM, the ANH group exhibited less favorable RFS [median survival time (MST), 12.1 vs. 18.1 months; P=0.097] and DSS (MST, 32.1 vs. 50.5 months; P=0.097) compared with the STD group; however, these differences were not statistically significant. In conclusion, while ANH was not as harmful as ABT, it exhibited potentially more negative effects on long-term postoperative outcomes in PDAC than STD.
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| S-EPMC10045975 | biostudies-literature
Project description:BackgroundPancreatic cancer (PC) continues to rank as one of the deadliest forms of cancer, with the majority of patients being diagnosed with unresectable disease. The implementation of cryoablation-based comprehensive treatment is expected to lead to a reduction in tumor size and potentially achieve complete resection. However, the availability of systematic and evidence-based treatment guidelines for cryoablation in pancreatic cancer is currently limited.Materials and methodsA computerized search was conducted in the Medline, Embase, Cochrane Library databases, and Clinicaltrials to retrieve studies published from August 1987 to June 2023. The perioperative outcomes and long-term survival of patients with locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (mPC) who underwent cryosurgery were systematically collected. Heterogeneity was assessed using the Cochran's Q test, and a funnel plot was implemented to evaluate publication bias. Data were pooled and analyzed using Stata 14.0 software. The Newcastle-Ottawa Quality Assessment Form tool was employed for quality evaluation.Results9 studies including 368 patients were identified. The pooled overall incidence rate was 4% (95%CI: 0-14%; I²=54.06%) for acute pancreatitis, 0% (95%CI: 0-0%; I²=0.0%) for delayed gastric emptying, 0% (95%CI: 0-1%; I²=0.0%) for postoperative pancreatic fistula (POPF) or bile leakage, 2% (95%CI:0-5%; I²=0.0%) for bleeding, and 4% (95%CI: 0-12%; I²=70.46%) for fever. Our subgroup analysis revealed that the percutaneous treatment group had a lower incidence of complications compared to laparotomy, but had higher incidences of POPF, bleeding, and pancreatitis than the intraoperative group. Median overall survival (OS) varied from 5 to 16.2 months. The median survival rates at 6, 12, 24, and 36 months for patients who underwent cryosurgery were as follows: 94.9%, 64.8% (range: 4.8%-63.1%), 22.80%, and 9.5%, respectively.ConclusionWith the advancements in cryoablation and anti-tumor therapy, cryoablation emerges as a promising treatment modality for patients with unresectable pancreatic cancer. According to existing literature, the combination of cryoablation with radioactive particle implantation or immunotherapy has demonstrated considerable efficacy and safety. However, while the majority of included data is derived from retrospective studies, it is imperative to conduct larger sample sizes or prospective trials for further validation.
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Project description:Advances in early detection and treatment have led to a growing population of female cancer survivors, many of whom are of working age. We examined the relationship between cancer and long-term (>5 years) employment outcomes in a nationally representative sample of working-age women in the United States. Data from nine waves of the Health and Retirement Study were used to examine employment status and weekly hours worked among cancer survivors (n = 483) and women without cancer (n = 6605). We used random slope regression models to estimate the impact of cancer and occupation type on employment outcomes. There was no difference in employment status between cancer survivors and women without cancer at baseline; however, during follow-up, cancer survivors were more likely to be employed than women without cancer (odds ratio (OR) = 1.33, 95% confidence interval (CI): 1.11-1.58). Among 6-10-year survivors, professional workers were less likely (OR = 0.40, 95% CI: 0.21-0.74) to be employed than manual workers. Among >10-year survivors, professional workers averaged fewer weekly hours worked (-2.4 h, 95% CI: -4.4--0.47) than manual workers. The impact of cancer on long-term employment outcomes may differ by occupation type. Identifying the occupation-specific mechanisms associated with the return to work will be critical to developing targeted strategies to promote employment in the growing female cancer survivor population.
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Project description:An improvement in pancreatic cancer treatment represents an urgent medical goal. Late diagnosis and high intrinsic resistance to conventional chemotherapy has led to a dismal overall prognosis that has remained unchanged during the past decades. Increasing knowledge about the molecular pathogenesis of the disease has shown that genetic alterations, such as mutations of K-ras, and especially epigenetic dysregulation of tumor-associated genes, such as silencing of the tumor suppressor p16(ink4a), are hallmarks of pancreatic cancer. Here, we describe genes that are commonly affected by epigenetic dysregulation in pancreatic cancer via DNA methylation, histone acetylation or miRNA (microRNA) expression, and review the implications on pancreatic cancer biology such as epithelial-mesenchymal transition, morphological pattern formation, or cancer stem cell regulation during carcinogenesis from PanIN (pancreatic intraepithelial lesions) to invasive cancer and resistance development. Epigenetic drugs, such as DNA methyltransferases or histone deactylase inhibitors, have shown promising preclinical results in pancreatic cancer and are currently in early phases of clinical development. Combinations of epigenetic drugs with established cytotoxic drugs or targeted therapies are promising approaches to improve the poor response and survival rate of pancreatic cancer patients.
| S-EPMC4069312 | biostudies-literature