A multicenter retrospective observational NAPOLEON2 study of nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable pancreatic cancer.

Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer. However, there are limited clinical data on its efficacy and safety in the real-world. We therefore initiated a retrospective and prospective observational study (NAPOLEON-2). The results of the retrospective part were reported herein. In this retrospective study, we evaluated 161 consecutive patients who received NFF as second-or-later-line regimen. The main endpoint was overall survival (OS), and the other endpoints were response rate, disease control rate, progression-free survival (PFS), dose intensity, and adverse events (AEs). The median age was 67 years (range, 38-85 years). The median OS and PFS were 8.1 and 3.4 months, respectively. The objective response and disease control rates were 5% and 52%, respectively. The median relative dose intensity was 81.6% for nanoliposomal irinotecan and 82.9% for fluorouracil. Grade 3 or 4 hematological and nonhematological AEs occurred in 47 and 42 patients, respectively. Common grade 3 or 4 AEs included neutropenia (24%), anorexia (12%), and leukocytopenia (12%). Subanalysis of patients treated with second-line and third-or-later-line demonstrated no statistical significant difference in OS (7.6 months vs. 9.1 months, respectively; hazard ratio, 0.92; 95% confidence interval, 0.64-1.35; p = 0.68). In conclusion, NFF has acceptable efficacy and safety profile even in real-world clinical settings. The prospective study is in progress to validate these findings.

Comparison of recurrent biliary obstruction with the use of metal and plastic stents in EUS-guided biliary drainage: A propensity score-matched analysis.

Background and Objectives: In transpapillary biliary drainage, metal stents (MSs) exhibit a lower incidence of a biliary obstruction than plastic stents (PSs). However, few studies have compared recurrent biliary obstruction (RBO) when MSs and PSs are used in EUS-guided hepaticogastrostomy (EUS-HGS) and choledochoduodenostomy (EUS-CDS). We retrospectively evaluated the RBO for both stents in each procedure. Patients and Methods: : Between November 2012 and December 2020, 85 and 53 patients who underwent EUS-HGS and EUS-CDS for unresectable malignant biliary obstruction, respectively, were enrolled. Factors associated with RBO were assessed. Clinical outcomes were compared between the MS and PS groups using propensity score matching. Results: : The clinical success rate and procedure-related adverse events were similar in the MS and PS groups. Multivariate analysis identified the use of PS as a factor associated with RBO (EUS-HGS, P = 0.03; EUS-CDS, P = 0.02). After matching, the median time to RBO in EUS-HGS (MS: 313; PS: 125 days; P = 0.01) in the MS group was longer than that in the PS group. The cumulative incidence of RBO at 1, 3, and 6 months in the MS group was significantly lower than that in the PS group for EUS-HGS (MS: 4.0%, 8.2%, and 8.2%; PS: 12.4%, 24.9%, and 39.5%, respectively, P = 0.01). Conclusions: : MS exhibited a lower rate of RBO than PS for EUS-HGS and EUS-CDS.

Efficacy and safety of a novel anti-reflux metal stent during neoadjuvant chemotherapy for pancreatic cancer: A prospective multicenter exploratory study.

BACKGROUND/PURPOSE: The benefits of anti-reflux metal stents, used for treating biliary obstruction in patients receiving neoadjuvant chemotherapy (NAC) for pancreatic cancer, are yet unknown. Herein, the safety and efficacy of the novel duckbill-type anti-reflux metal stent (D-ARMS) were prospectively evaluated for biliary drainage. Additionally, the incidence of recurrent biliary obstruction (RBO) after placement of D-ARMS vs conventional covered self-expandable metal stents (CCSEMSs) was retrospectively compared. METHODS: Patients who received D-ARMS (n = 33) for treatment of distal biliary obstruction before NAC between September 2019 and January 2021 and those that received CCSEMSs (n = 38) between January 2013 and August 2019 were included in the historical control group. Technical and clinical successes, rate of RBO, and cumulative incidence of RBO were compared between the two groups. RESULTS: The technical success rate was 100% for both the D-ARMS and CCSEMS groups, and the clinical success rate were not significantly different (93.9% and 89.5%, respectively; P = .68). In the multivariate analysis, D-ARMS was identified as the independent factor for cumulative incidence of RBO (P = .03). The cumulative incidence of RBO was significantly lower in the D-ARMS group than that in the CCSEMS group (P = .04). CONCLUSIONS: D-ARMS is safe and effective for patients receiving NAC.

High resolution imaging of ultrafine bubbles in water by Atmospheric SEM-CL.

Various analytical methods such as high-resolution observation of ultrafine bubbles in water are required to clarify the mechanisms and interrelationships of various effects brought about by ultrafine bubbles. In this study, we used atmospheric scanning electron microscopy-cathodoluminescence (ASEM-CL) method for observing ultrafine bubbles in water. ASEM can observe samples in water, and the fine electron beam provides high spatial resolution. Furthermore, the gas in the bubble can be estimated from the CL emission spectrum. We have measured characteristics such as bubble size and particle number density. Also, the CL spectra has shown that the ultrafine bubbles contained nitrogen.

Prognostic significance of extracellular volume fraction with equilibrium contrast-enhanced computed tomography for pancreatic neuroendocrine neoplasms.

BACKGROUND: /Objectives: Identifying reliable pretreatment imaging biomarkers for pancreatic neuroendocrine neoplasm (PanNEN) is a key imperative. Extracellular volume (ECV) fraction quantified with equilibrium contrast-enhanced CT can be easily integrated into routine examinations. This study aimed to determine whether ECV fraction with equilibrium contrast-enhanced computed tomography (CECT) could predict long-term outcomes in patients with PanNEN. METHODS: This study was a retrospective observational study of 80 patients pathologically diagnosed with PanNEN at a single institution. ECV fraction of the primary lesion was calculated using region-of-interest measurement within PanNEN and the aorta on unenhanced and equilibrium CECT. The impact of clinical factors and tumor ECV fraction on progression-free survival (PFS) and overall survival (OS) was assessed with univariate and multivariate analyses using Cox proportional hazards models. The correlation between WHO classification and tumor ECV fraction was evaluated using Kendall rank correlation coefficients. RESULTS: PFS and OS rates were estimated as 93.4% and 94.6%, 78.7% and 86.2%, 78.7% and 77.0%, and 78.7% and 66.6% at 1, 3, 5, and 10 years, respectively. Multivariate analysis revealed that Union for International Cancer Control (UICC) stage (hazard ratio [HR] = 3.95, P = 0.003), WHO classification (HR = 12.27, P = 0.003), and tumor ECV fraction (HR = 11.93, P = 0.039) were independent predictors of PFS. Patient age (HR = 1.11, P < 0.001), UICC stage (HR = 3.14, P = 0.001), and tumor ECV fraction (HR = 5.27, P = 0.024) were independent significant variables for predicting OS. Tumor ECV fraction had a weak inverse relationship with WHO classification (P = 0.045, τ = -0.178). CONCLUSIONS: ECV fraction determined by equilibrium CECT and UICC stage may predict survival in patients with PanNEN.

Factors Associated with the Technical Success of Bilateral Endoscopic Metallic Stenting with Partial Stent-In-Stent Placement in Patients with Malignant Hilar Biliary Obstruction.

BACKGROUND: Bilateral biliary drainage decreases the risk of cholangitis, but bilateral endoscopic metallic stenting is technically challenging. AIM: We retrospectively evaluated the factors associated with successful bilateral self-expanding metal stent (SEMS) placement using the partial stent-in-stent (PSIS) method for malignant hilar biliary obstruction and also assessed the safety and efficacy of this technique. METHODS: From April 2010 to February 2016, 47 consecutive patients (mean age, 73.0 ± 8.6 years; 32 males and 15 females) underwent PSIS placement for malignant hilar biliary obstruction in our hospital. The technical success of PSIS, clinical response, and complications were investigated. Factors associated with the technical success of PSIS were assessed. Using a propensity score-matched analysis, we compared the procedure time, clinical response, complications, stent patency, and survival time in 17 matched patients treated with bilateral SEMS placement using a SEMS delivery system of <6.0 or ≥6.0 Fr. RESULTS: The technical success rate was 77%. The clinical response rate was 91%, and the complication rate was 26%. Regarding complications, pancreatitis occurred in 5 patients (11%), cholangitis in 6 (13%), and cholecystitis in 1 (2%). A multiple logistic regression analysis identified the use of a SEMS with a delivery system < 6.0 Fr as a factor associated with technical success (P = 0.033; odds ratio, 10.769; 95% confidence interval, 1.205-96.212). In the 17 matched patients assigned according to the SEMS delivery system size, the procedure time was significantly shorter in those with a delivery system size < 6.0 Fr than in those with ≥6.0 Fr (P < 0.01). There were no significant differences in the clinical response, complication rate, stent patency, or survival time between the two groups. CONCLUSION: Using a delivery system < 6.0 Fr in size helped improve the technical success and reduced the procedure time for the placement of a SEMS by the PSIS method.

A high­fructose diet induces epithelial barrier dysfunction and exacerbates the severity of dextran sulfate sodium­induced colitis.

Excessive fructose intake is a risk factor for gut symptoms in patients with inflammatory bowel disease, however, its effect on the intestinal tract has not been evaluated previously. The present study investigated the impact of a high­fructose diet (HFD) on intestinal barrier function in mice with experimental colitis. C57/BL6 mice were provided with either a HFD or control diet and either plain drinking water or water containing 1% dextran sulfate sodium (DSS) for 2 weeks. The disease activity index (DAI), pathological scores and expression of inflammatory cytokines were compared among the groups, and the proportions of fecal bacteria in the colon were analyzed. The body weight and colon length were significantly decreased, and the DAI and pathological scores were significantly increased in the DSS/HFD­treated mice compared with the non­DSS­treated and control diet mice. Regarding the expression of inflammatory cytokines, the levels of interleukin (IL)­6, IL­1ß and tumor necrosis factor­α were significantly increased, and the expression of the tight junction protein occludin was significantly decreased in the DSS/HFD­treated mice. The total bacterial count was increased in the HFD mice. Taken together, these results indicate that an HFD resulted in the deterioration of intestinal barrier function and increased susceptibility to DSS­induced colitis.

Diagnostic efficacy of liquid-based cytology for solid pancreatic lesion samples obtained with endoscopic ultrasound-guided fine-needle aspiration: Propensity score-matched analysis.

BACKGROUND AND AIM: There is a paucity of data on the diagnostic efficacy of liquid-based cytology (LBC) for pancreatic samples obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Using propensity score matching, we retrospectively analyzed the additional diagnostic value of LBC compared to a conventional Papanicolaou smear (CPS) for samples of solid pancreatic lesions obtained by EUS-FNA. METHODS: This cohort study included 126 matched patients who underwent initial EUS-FNA for solid pancreatic lesions between January 2009 and August 2014. CPS was used for cytology of EUS-FNA samples obtained until May 2012 (63 patients). Subsequently, LBC was used for cytological analysis (63 patients). Diagnostic yields of CPS and LBC for malignancy were compared. Risk factors for cytological misdiagnosis with LBC were investigated. RESULTS: Overall rate of malignancy was 86% after matching. LBC had higher diagnostic sensitivity and accuracy than CPS (96.6% vs 84.0%, P = 0.03; and 96.8% vs 87.3%, P = 0.05). LBC was significantly more sensitive for diagnosing pancreatic head lesions (96.4% vs 78.1%, P = 0.04). The sensitivity for pancreatic ductal adenocarcinoma (PDAC) with LBC was higher (98.1% vs 83.0%, P = 0.009). Multivariate analysis revealed that malignant tumors other than PDAC (P = 0.004) and lesion size ≤20 mm (P = 0.046) were risk factors for LBC misdiagnosis in all participants. CONCLUSIONS: For solid pancreatic lesions, LBC of EUS-FNA samples contributes to the diagnosis of malignancy. Malignant tumors other than PDAC and small tumors are difficult to diagnose using EUS-FNA and LBC.

Fecal Human Neutrophil Peptide Levels Correlate with Intestinal Inflammation in Ulcerative Colitis.

BACKGROUND/AIM: Fecal markers have recently been found to provide convenient and noninvasive assessment of intestinal inflammation in inflammatory bowel disease (IBD). In this study, we examined the clinical significance of fecal human neutrophil peptides (F-HNP) in the evaluation of IBD disease activity. METHODS: This study enrolled 70 patients with IBD, consisting of 45 patients with ulcerative colitis (UC), 25 patients with Crohn's disease (CD), and 11 non-IBD controls. Stools samples were evaluated for the association between F-HNP concentration and disease and endoscopic activity in each group and the correlation between F-HNP and fecal calprotectin (F-CP) concentrations. RESULTS: Median F-HNP levels were as follows: UC: 25.6 ng/ml; CD: 20.1 ng/ml; and non-IBD controls: 4.9 ng/ml. F-HNP levels were significantly higher in each IBD group, especially in the UC group, than in the control group. In the UC group, both F-HNP and F-CP levels were significantly higher during active disease compared to the remission phase. Both markers were significantly correlated with the Mayo endoscopic score, although the correlation was stronger for F-HNP than for F-CP (r = 0.66 vs. r = 0.54). CONCLUSION: F-HNP is a noninvasive marker that is useful for evaluating UC endoscopic activity.

Primary squamous cell carcinoma of the duodenum effectively treated with TS-1: a case report.

An 89-year-old man was admitted to our hospital for thorough investigation of refractory diabetes mellitus, which revealed primary squamous cell carcinoma of the duodenum. After two courses of chemotherapy, follow-up esophagoduodenogastroscopy and duodenal biopsy showed no evidence of tumor. No findings were suggestive of recurrence of the primary lesion 19 months after starting chemotherapy. This case suggests that chemotherapy including TS-1 may be effective for treating unresectable primary squamous cell carcinoma of the duodenum.

Detection of sentinel nodes in gastric cancer by indocyanine green fluorescence imaging.

BACKGROUND/AIMS: The sentinel nodes (SN) are the first nodes to receive lymphatic drainage from a primary tumor. The SN concept is useful to avoid unnecessary resection in gastric cancer. Indocyanine green (ICG) fluorescence imaging is a new method for detecting SN and we herein examined the usefulness of this technology. METHODOLOGY: The subjects comprised 39 cT1-2N0 gastric cancer patients who underwent standard surgery from 2006 to 2009. 0.8 mL ICG (1%) was injected into the submucosa around the tumor two days preoperatively (Preop group) or intraoperatively (Intraop group) by endoscopy. SN were postoperatively identified by fluorescence imaging and the accuracy of this method compared to the dye method was investigated for 76 patients treated from 2000-2004. RESULTS: SN was detected as fluorescence-positive nodes (FN) and the mean FN number was 9.3±6.4. The specificity was 100% and all metastatic lymph nodes were detected as FN in three patients. The mean number of FNs was 7.2 in the preop group and 12.5 in the postop group (p=0.032).The FN method was associated with a low false negative rate, same as the dye method. CONCLUSIONS: SN mapping using ICG fluorescence imaging has high accuracy and this compound can be injected preoperatively to detect SN.

Molecular cloning of a cDNA encoding a soluble protein in the coral exoskeleton.

Organic substances were extracted from the calcified exoskeleton of the reef coral Galaxea fascicularis. In an SDS-PAGE analysis of the extract, a protein with an apparent molecular mass of 53 kDa was detected as well as two other weaker bands. A Ca2+ overlay analysis failed to find a Ca2+-binding protein in the extract. Periodic acid Schiff staining indicated that the 53 kDa protein was glycosylated. A cDNA containing the entire open reading frame for this protein was obtained. Analysis of the deduced protein sequence suggests that the protein, named galaxin, is synthesized as a precursor consisting of a signal peptide, a propeptide sequence, and a mature protein of 298 amino acids. Galaxin exhibits a novel amino acid sequence which is characterized by a tandem repeat structure. Galaxin transcripts were detected in the adult coral, but not in planktonic larvae.