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Stereotactic body radiation therapy (SBRT) is an important treatment option for pancreatic cancer, which is known to be one of the malignancies with the worst prognosis. However, the high radiation doses delivered during SBRT may cause damage to adjacent radiosensitive organs. To minimize such damage, fiducial markers are used for localization during SBRT for pancreatic cancer. The development of endoscopic ultrasound (EUS) has enabled fiducial markers to be inserted into the pancreas using an EUS fine-needle aspiration (FNA) needle, unlike in the past when percutaneous placement was generally performed. For successful EUS-guided fiducial marker placement, it is necessary for the fiducial markers to be loaded within the EUS-FNA needles to have a low probability of complications and a low migration risk, and to be stably observed in SBRT imaging. A systematic review has shown that the technical success rate of EUS-guided fiducial marker placement is 96.27%, whereas the fiducial marker migration and adverse event rates are 4.33% and 4.85%, respectively. Nonetheless, standardized techniques for fiducial marker placement and the characteristics of optimal fiducial markers have not yet been established. This review will introduce the characteristics (e.g., materials and shapes) of fiducial markers used in fiducial marker placement for pancreatic cancer and will discuss conventional techniques along with their success rates, difficulties, and adverse events. [ABSTRACT FROM AUTHOR]

Background/Aim: There are currently no data on the relative retention rates of the Instinct clip, Resolution clip, and QuickClip2Long. Also, it is unknown whether retention rate differs when clips are applied to ulcerated rather than normal mucosa. The aim of this study is to compare the retention rates of three commonly used endoscopic clips. Materials and Methods: Six pigs underwent upper endoscopy with placement of one of each of the three types of clips on normal mucosa in the gastric body. Three mucosal resections were also performed to create “ulcers.” Each ulcer was closed with placement of one of the three different clips. Repeat endoscopy was performed weekly for up to 4 weeks. Results: Only the Instinct and Resolution clips remained attached for the duration of the study (4 weeks). At each time point, a greater proportion of Instinct clips were retained on normal mucosa, followed by Resolution clips. QuickClip2Long had the lowest retention rate on normal mucosa. Similar retention rates of Instinct clips and Resolution clips were seen on simulated ulcers, although both were superior to QuickClip2Long. However, the difference did not reach statistical significance. All QuickClip2Long clips were dislodged at 4 weeks in both the groups.Conclusions: The Resolution and Instinct clips have comparable retention rates and both appeared to be better than the QuickClip2Long on normal mucosa‑simulated ulcers; however this did not reach statistical significance. Both the Resolution clip and the Instinct clip may be preferred in clinical situations when long‑term clip attachment is required, including marking of tumors for radiotherapy and anchoring feeding tubes or stents. Either of the currently available clips may be suitable for closure of iatrogenic mucosal defects without features of chronicity. [ABSTRACT FROM AUTHOR]

High molecular weight poly(ε-caprolactone)s (PCL) were synthesized via zwitterionic polymerization of ε-caprolactone initiated with N-heterocyclic carbenes. Ring-opening polymerization of ε-caprolactone (1 M) with carbenes 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene (1) or 1,3,4,5-tetramethylimidazol-2-ylidene (3) affords cyclic PCL with molecular weights up to Mn= 114 000 g/mol. Crystallization of the cyclic PCL was investigated by synchrotron small-angle X-ray scattering experiments and differential scanning calorimetry. High molecular weight cyclic poly(ε-caprolactone) crystallizes with a similar lamellar thickness and long period spacing as linear poly(ε-caprolactone), but the crystallization of cyclic poly(ε-caprolactone) is faster than that of linear poly(ε-caprolactone) for molecular weights greater than 75 000 g/mol. These results imply that the polymer topology does not have a significant influence on the crystal structure or morphology but can have a significant influence on the rate of crystallization from the melt. [ABSTRACT FROM AUTHOR]

The zwitterionic ring-opening polymerization of lactide initiated by N-heterocyclic carbenes generates cyclic polylactides with well-defined molecular weights between Mn = 5000 and 30 000 g/mol with narrow polydispersities (Mw/Mn ≤ 1.31). These zwitterionic polymerizations are extremely rapid (kp = 48.7 M-1 s-1), but also exhibit exceptional control of molecular weight and molecular weight distribution. The unusual kinetic features of these zwitterionic polymerizations are illuminated with kinetic and mechanistic investigations, which implicate a mechanism that involves a slow initiation step (second order.in [M]), a propagation step (first order in [M]) that is much faster than initiation (kj = 0.274 M-2 s-1), cyclization (kc = 0.0575 s-1), and depropagation (kd = 0.208 s-1). Numerical and stochastic simulations of the kinetic data provide a kinetic rationale for the evolution of molecular weight with monomer conversion: the molecular weights increase with increasing monomer conversion, exhibit a nonzero intercept near 0% monomer conversion, and are relatively insensitive to the initial monomer-to-initiator ratio. The observed narrow molecular weight distributions are due to a high rate of propagation relative to cyclization and chain transfer. Kinetic simulations define the kinetic criteria under which the active zwitterions remain in solution; these simulations were substantiated by chain-extension experiments, which provide experimental evidence for chain extension of the zwitterions and reinitiation by the N-heterocyclic carbenes liberated upon macrocyclization. The kinetic model rationalizes some of the unique features of zwitterionic ring-opening polymerization and provides a useful mechanistic framework to optimize these polymerizations as a strategy to generate well-defined cyclic polyesters. [ABSTRACT FROM AUTHOR]

A response by Doctors Kevin R. Riggs, Eun Ji Shin, and Jodi B. Segal to a letter to the editor about their article "Prevalence and cost of office visits prior to colonoscopy for colon cancer screening" in a 2016 issue is presented.

Background/Aims Cholangiocarcinoma (CCA) has a grave prognosis, and its prevention is crucial in improving the outcomes. To evaluate the risk factors for CCA, we conducted a nationwide retrospective cohort study. Methods We created a dataset of 3,000,000 adults who underwent health screening in 2009 or 2010 in South Korea, and their medical records were followed up until December 2020. Individuals with cancer (n=65,282), those with incomplete data (n=125,899), and those aged <40 years (n=126,768) were excluded. The factors considered were age, sex, body mass index (BMI), smoking, alcohol consumption, socioeconomic status, and comorbidities, including hepatitis B (HBV), hepatitis C (HCV), liver cirrhosis, primary sclerosing cholangitis (PSC), cholelithiasis, choledocholithiasis, acute cholecystitis, ulcerative colitis (UC), Crohn's disease (CD), type 2 diabetes (T2D), and metabolic syndrome. The univariate Cox proportional hazards regression model was used and Kaplan-Meier analysis were performed. Results We identified 7,018 CCA cases and 2,675,033 controls. Among the risk factors for CCA, age ＞60 years (hazard ratio (HR) 9.548, 95% confidence interval (CI) 9.360-9.739), male sex (HR 1.949, 95% CI 1.922-1.976), BMI <18.5 kg/m2 (HR 2.535, 95% CI 2.479-2.592), liver cirrhosis (HR 2.209, 95% CI 2.138-2.282), PSC (HR 1.746, 95% CI 1.574-1.936), and T2D (HR 1.983, 95% CI 1.958-2.008) showed significantly high HRs. Among these factors, BMI is the most modifiable. Conclusion There was an inverse association between BMI and CCA risk. Further research is needed to clarify this finding and elucidate the role of central obesity in CCA carcinogenesis. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Ablation of Barrett's esophagus (BE) is the preferred approach for the treatment of neoplasia without visible lesions. Limited data on cryoballoon ablation (CBA) suggest its potential clinical utility. We evaluated the safety and efficacy of CBA in a multicenter study of patients with neoplastic BE. METHODS: In a prospective clinical trial, 11 academic and community centers recruited consecutive patients with BE of 1-6 cm length and low-grade dysplasia, high-grade dysplasia (HGD), or intramucosal adenocarcinoma (ImCA) confirmed by central pathology. Patients with symptomatic pre-existing strictures or visibleBElesions had dilation or endoscopic mucosal resection (EMR), respectively, before enrollment. A nitrous oxide cryoballoon focal ablation system was used to treat all visible columnar mucosa in up to 5 sessions. Study end points included complete eradication of all dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1 year. RESULTS: One hundred twenty patients with BEwith ImCA (20%),HGD(56%), or low-grade dysplasia (23%) were enrolled. In the intention-to-treat analysis, the CE-D and CE-IM rates were 76% and 72%, respectively. In the per-protocol analysis (94 patients), the CE-D and CE-IM rates were 97% and 91%, respectively. Postablation pain was mild and short lived. Fifteen subjects (12.5%) developed strictures requiring dilation. One patient (0.8%) with HGD progressed to ImCA, which was successfully treated with EMR. Another patient (0.8%) developed gastrointestinal bleeding associated with clopidogrel use. One patient (0.8%) had buried BE with HGD in 1 biopsy, not confirmed by subsequent EMR. DISCUSSION: In patients with neoplastic BE, CBA was safe and effective. Head-to-head comparisons between CBA and other ablation modalities are warranted (clinicaltrials.gov registration NCT02514525). [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning prevalence and cost of office visits prior to colonoscopy for colon cancer screening.

Background and Study Aim: Standard endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) procedures involve use of no-suction or suction aspiration techniques. A new aspiration method, the stylet slow-pull technique, involves slow withdrawal of the needle stylet to create minimum negative pressure. The aim of this study was to compare the sensitivity of EUS-FNA using stylet slow-pull or suction techniques for malignant solid pancreatic lesions using a standard 22-gauge needle.Patients and Methods: Consecutive patients presenting for EUS-FNA of pancreatic mass lesions were randomized to the stylet slow-pull or suction techniques using a 22-gauge needle. Both techniques were standardized for each pass until an adequate specimen was obtained, as determined by rapid on-site cytology examination. Patients were crossed over to the alternative technique after four nondiagnostic passes.Results: Of 147 patients screened, 121 (mean age 64 ± 13.8 years) met inclusion criteria and were randomized to the stylet slow-pull technique (n = 61) or the suction technique (n = 60). Technical success rates were 96.7 % and 98.3 % in the slow-pull and suction groups, respectively (P > 0.99). The sensitivity for malignancy of EUS-FNA was 82 % in the slow-pull group and 69 % in the suction group (P = 0.10). The first-pass diagnostic rate (42.6 % vs. 38.3 %; P = 0.71), acquisition of core tissue (60.6 % vs. 46.7 %; P = 0.14), and the median (range) number of passes to diagnosis (2 1 2 3 vs. 1 1 2; P = 0.71) were similar in the slow-pull and suction groups, respectively.Conclusions: The stylet slow-pull and suction techniques both offered high and comparable diagnostic sensitivity with a mean of 2 passes required for diagnosis of solid pancreatic lesions. The endosonographer may choose either technique during FNA. [ABSTRACT FROM AUTHOR]

There have been no reports describing the effects of cancer cell-derived extracellular vesicles (EVs) on threedimensional organoids. In this study, we delineated the proneoplastic effects of esophageal adenocarcinoma (EAC)-derived EVs on gastric organoids (gastroids) and elucidated molecular mechanisms underlying these effects. EVs were identified using PKH-67 staining. Morphologic changes, Ki-67 immunochemistry, cell viability, growth rates, and expression levels of miR-25 and miR-210, as well as of their target mRNAs, were determined in gastroids co-cultured with EAC-derived extracellular vesicles (c-EVs). C-EVs were efficiently taken up by gastroids. Notably, c-EV-treated gastroids were more crowded, compact, and multilayered and contained smaller lumens than did those cultured in organoid medium alone or in EAC-conditioned medium that had been depleted of EVs. Moreover, c-EV-treated gastroids manifested increased proliferation and cellular viability relative to medium-only or EV-depleted controls. Expression levels of miR-25 and miR-210 were significantly higher, and those of PTEN and AIFM3 significantly lower, in c-EV-treated versus medium-only or EV-depleted control groups. Inhibitors of miR-25 and miR-210 reversed the increased cell proliferation induced by c-exosomes in co-cultured gastroids by lowering miR-25 and miR-210 levels. In conclusion, we have constructed a novel model system featuring the co-culture of c-EVs with three-dimensional gastroids. Using this model, we discovered that cancer-derived EVs induce a neoplastic phenotype in gastroids. These changes are due, at least in part, to EV transfer of miR-25 and miR-210. [ABSTRACT FROM AUTHOR]

The article focuses on studying the role of long non coding RNA (IncRNA) in development and progression of oesophageal adenocarcinoma (EAC). It mentions the use of several techniques including RNA sequencing and reverse transcriptase-polymerase chain reaction (RT-PCR) to show abnormally upregulated level of some IncRNAs in EAC patients. It also reports that these IncRNA may cause changes in chromatin and nucleosome assembly which results in EAC.