Cancers, Vol. 10, Pages 467: Circulating Tumor and Invasive Cell Gene Expression Profile Predicts Treatment Response and Survival in Pancreatic Adenocarcinoma

Cancers, Vol. 10, Pages 467: Circulating Tumor and Invasive Cell Gene Expression Profile Predicts Treatment Response and Survival in Pancreatic Adenocarcinoma

Cancers doi: 10.3390/cancers10120467

Authors: Kenneth H. Yu Mark Ricigliano Brian McCarthy Joanne F. Chou Marinela Capanu Brandon Cooper Andrew Bartlett Christina Covington Maeve A. Lowery Eileen M. O'Reilly

Previous studies have shown that pharmacogenomic modeling of circulating tumor and invasive cells (CTICs) can predict response of pancreatic ductal adenocarcinoma (PDAC) to combination chemotherapy, predominantly 5-fluorouracil-based. We hypothesized that a similar approach could be developed to predict treatment response to standard frontline gemcitabine with nab-paclitaxel (G/nab-P) chemotherapy. Gene expression profiles for responsiveness to G/nab-P were determined in cell lines and a test set of patient samples. A prospective clinical trial was conducted, enrolling 37 patients with advanced PDAC who received G/nab-P. Peripheral blood was collected prior to treatment, after two months of treatment, and at progression. The CTICs were isolated based on a phenotype of collagen invasion. The RNA was isolated, cDNA synthesized, and qPCR gene expression analyzed. Patients were most closely matched to one of three chemotherapy response templates. Circulating tumor and invasive cells’ SMAD4 expression was measured serially. The CTICs were reliably isolated and profiled from peripheral blood prior to and during chemotherapy treatment. Individual patients could be matched to distinct response templates predicting differential responses to G/nab-P treatment. Progression free survival was significantly correlated to response prediction and ΔSMAD4 was significantly associated with disease progression. These findings support phenotypic profiling and ΔSMAD4 of CTICs as promising clinical tools for choosing effective therapy in advanced PDAC, and for anticipating disease progression.

https://ift.tt/2POyTus

Single‐operator Peroral Cholangioscope in Treating Difficult Biliary Stones: A Systematic Review and Meta‐analysis

Abstract

Objectives

Current evidence supporting the utility of single‐operator peroral cholangioscope (SOPOC) in the management of difficult bile duct stones is limited. We conducted the present systematic review and meta‐analysis to evaluate the efficacy and safety of SOPOC in treating difficult bile duct stones.

Methods

We searched studies up to April 2018, using MEDLINE, EMBASE, the Cochrane Library, and Google Scholar. Quality assessment of the studies was completed with the Newcastle‐Ottawa Scale. The main outcomes were complete stone clearance rate, single‐session stone clearance rate, number of endoscopic sessions needed for stone clearance, and adverse events. We calculated the pooled estimates with random‐effects models. Potential publication bias was assessed.

Results

Twenty‐four studies involving 2786 patients met the inclusion criteria. The pooled proportion of patients with complete stone clearance was 94.3% (95% confidence interval [95% CI]: 90.2%‐97.5%). Single‐session stone clearance was achieved in 71.1% (95% CI: 62.1%‐79.5%) of the pooled patients. The pooled number of sessions needed for stone clearance was 1.26 (95% CI: 1.17‐1.34). The pooled adverse event rate was 6.1% (95% CI: 3.8%‐8.7%). Potential publication bias was detected but had no significant influence on the results.

Conclusions

SOPOC is an effective and safe treatment for difficult bile duct stones when conventional methods have failed. More randomized controlled trials are warranted to confirm the results.

This article is protected by copyright. All rights reserved.

https://ift.tt/2PSdy3t

Negative parenting modulates the association between mother’s DNA methylation profiles and adult offspring depression

Abstract

This study aimed to examine whether the relationship between mothers' DNA methylation profiles and offspring's depression is modulated by negative parenting. The participants were 35 African‐American mother–offspring dyads. Young adult offspring (19 females; age = 17–29.5 years) were assessed on depressive symptoms, and mothers (36–51 years) were assessed on negative parenting. Methyl‐binding domain (MBD) sequencing was used to assay genome‐wide DNA methylation in peripheral T lymphocytes. Controlling for the effect of offspring's DNA methylation, mothers' DNA methylation was positively associated with offspring's depression. Hypermethylation of a subset of the epigenetic markers was associated with increased negative parenting. Negative parenting was positively correlated with offspring's depression as well, suggesting that negative parenting may be a modulator between the mother's epigenome and offspring's depression. This study is one of the first investigations of the modulating role of parenting behavior in associations between the mother's epigenome and offspring's depression.

https://ift.tt/2DGKwMS

Systemic Approach to Prevent Inadvertent Perfusion in Eyes with Extensive Choroidal Detachment, Suprachoroidal Fluid, and Hypotony During Pars Plana Vitrectomy

Abstract

Introduction

Rhegmatogenous retinal detachment (RRD) with extensive choroidal detachment (CD), suprachoroidal fluid (SCF), and lower intraocular pressure (IOP) markedly increase the difficulty of pars plana vitrectomy (PPV) because it makes the insertion and placement of the trocar cannulas for PPV time-consuming and technically challenging. In this study, we developed a systemic approach that avoids the risks of sclerotomy or using a longer trocar to help in the safe placement of the trocar cannulas in order to prevent inadvertent fluid/air perfusion during PPV in RRD eyes with extensive CD, SCF, and hypotony.

Methods

This is a prospective case series study. Consecutive patients diagnosed with RRD with extensive CD, SCF, and hypotony were recruited. The main steps included injecting transconjunctival intravitreal fluid to increase IOP and enable the passive egress of SCF into the subconjunctival space, creating and broadening the inner opening for the trocar cannulas, transillumination with an endoillumination light pipe, and indentation of the infusion cannula to create maximum visual exposure of the inner segment and help peripheral shaving around the infusion tip. Main outcomes: the success rate of the infusion placement into the vitreous cavity, surgical duration, intra- and postoperative complications, and functional and anatomical outcomes.

Results

Thirty-eight patients (38 eyes) were included. The first-time success rate of cannula placement into the vitreous cavity was 100%, with a mean surgical duration of 8.5 ± 1.8 min. No intra- or postoperative complications related to the approach were observed. Significant vision improvement was noted in 68.4% (26/38) of the patients at the final follow-up. The primary and final retinal reattachment rates were 94.7% (36/38) and 100% (38/38), respectively.

Conclusion

This systemic approach is a feasible option to ensure the safe placement of trocar cannulas and prevent inadvertent perfusion during small-gauge PPV in RRD eyes with extensive CD, SCF, and hypotony, without the need for a draining sclerotomy, a longer trocar, or a sharp clearing of the cannula tip.

https://ift.tt/2QiojLR

An a priori approach for the accurate prediction of amide exchange in the fast limit reveals thrombin allostery

Amide hydrogen/deuterium exchange mass spectrometry (HDXMS) of proteins has become extremely popular for identifying ligand binding sites, protein-protein interactions, intrinsic disorder, and allosteric changes upon protein modification. Such phenomena are revealed when amide exchange is measured in the fast-limit, that is within a few minutes of exchange in deuterated buffer. The HDXMS data have a resolution of the length of peptides and are difficult to interpret because many different phenomena lead to changes in HDX.

https://ift.tt/2Rb5o2H

Antiviral Therapy Reduces Hepatocellular Carcinoma Recurrence in Patients With Low HBV-DNA Levels: A Randomized Controlled Trial

Background: Despite antiviral treatment has been shown to reduce hepatocellular carcinoma (HCC) recurrence after curative treatment for hepatitis B virus (HBV)-related HCC in patients with high preoperative HBV-DNA levels, it is still unclear whether antiviral therapy is useful in reducing recurrence in patients with low preoperative HBV-DNA levels. Methods: In this randomized controlled trial, 200 patients who underwent curative resection for HCC with low baseline HBV-DNA levels were randomly assigned to receive preemptive antiviral therapy or not. The primary endpoints were recurrence-free survival. This study was censored on March 31, 2015 when all surviving patients had a minimum follow-up of 60 months. The analysis was done on an intention-to-treat basis. Results: The baseline clinical, laboratory, and tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year recurrence-free survival rates for the antiviral group and the control group were 85.9%, 55.2%, and 52.0% and 80.6%, 40.9%, and 32.3%, respectively. The corresponding overall survival rates for the 2 groups were 94.0%, 75.7%, and 64.1% and 90.0%, 62.4%, and 43.7%, respectively. The recurrence-free survival and overall survival for the antiviral group were significantly better than the control group (P = 0.016, P = 0.004, respectively). After adjusting for confounding prognostic factors in a Cox model, the relative risks of recurrence and death for antiviral treatment were 0.601 [95% confidence interval (CI), 0.409–0.884; P = 0.010] and 0.509 (95% CI, 0.333–0.778; P = 0.002), respectively. Antiviral therapy was an independent protective factor of late tumor recurrence (hazard ratio [HR] = 0.316, 95% CI 0.157–0.637; P = 0.001) but not of early tumor recurrence (HR = 0.782, 95% CI, 0.493–1.240; P = 0.296). Conclusions: In patients with low preoperative HBV-DNA levels, antiviral therapy significantly reduced HCC recurrence after R0 hepatic resection.

https://ift.tt/2qDByYZ

Functional Trajectories Before and After Major Surgery in Older Adults

Objectives: We hypothesized that distinct sets of functional trajectories can be identified in the year before and after major surgery, with unique transition probabilities from pre to postsurgical functional trajectories, and that outcomes would be better among participants undergoing elective versus nonelective surgery. Background: Major surgery is common and can be highly morbid in older persons. The relationship between the course of disability (ie, functional trajectory) before and after surgery in older adults has not been well-studied for most operations. Methods: Prospective cohort study of 754 community-living persons 70 years or older. The analytic sample included 250 participants who underwent their first major surgery during the study period. Results: Before surgery, 4 functional trajectories were identified: no disability (n = 60, 24.0%), and mild (n = 84, 33.6%), moderate (n = 73, 29.2%), and severe (n = 33, 13.2%) disability. After surgery, 4 functional trajectories were identified: rapid (n = 39, 15.6%), gradual (n = 76, 30.4%), partial (n = 70, 28.0%), and little (n = 57, 22.8%) improvement. Rapid improvement was seen for n = 31 (51.7%) participants with no disability before surgery, but was uncommon among those with mild disability (n = 8, 9.5%) and was not observed in the moderate and severe trajectory groups. For participants with mild to moderate disability before surgery, gradual improvement (n = 46, 54.8%) and partial improvement (n = 36, 49.3%) were most common. Most participants with severe disability (n = 27, 81.8%) before surgery exhibited little improvement. Outcomes were better for participants undergoing elective versus nonelective surgery. Conclusions: Functional prognosis in the year after major surgery is highly dependent on premorbid function.

https://ift.tt/2QyE3XO