Endoscopic papillectomy could be rewarding to patients with early stage duodenal ampullary carcinoma?

BACKGROUND/PURPOSE: There is currently no consensus on the use of endoscopic papillectomy (EP) for early stage duodenal ampullary adenocarcinoma. This study aimed to evaluate the feasibility of EP for patients with early stage duodenal ampullary adenocarcinoma. METHODS: Patients who underwent EP for ampullary adenocarcinomas were investigated. Complete and clinical complete resection rates were evaluated. Clinical complete resection was defined as either complete resection or resection with positive or unknown margins but no cancer in the surgically resected specimen, or no recurrence on endoscopy after at least a 1-year follow-up. RESULTS: Adenocarcinoma developed in 30 patients (carcinoma in situ [Tis]: 21, mucosal tumors [T1a(M)]: 4, tumors in the sphincter of Oddi [T1a(OD)]: 5). The complete resection rate was 60.0% (18/30) (Tis: 66.7% [14/21], T1a[M]: 50.0% [2/4], and T1a[OD]: 40.0% [2/5]). The mean follow-up period was 46.8 months. The recurrence rate for all patients was 6.7% (2/30). The clinical complete resection rates of adenocarcinoma were 89.2% (25/28); rates for Tis, T1a(M), and T1a(OD) were 89.4% (17/19), 100% (4/4), and 80% (4/5), respectively. CONCLUSIONS: EP may potentially achieve clinical complete resection of early stage (Tis and T1a) duodenal ampullary adenocarcinomas.

[Surgical Treatment of the Perforation of the Right Ventricle and Diaphragm by a Permanent Pacing Lead:Report of a Case].

An 97-year-old woman was diagnosed with complete atrioventricular block and underwent pacemaker implantation( PMI). Three days after the PMI, computed tomography revealed cardiac perforation and migration of the lead to the abdominal cavity. Surgical procedure through median sternotomy was performed, and the penetrated lead was removed. The holes of the right ventricle and diaphragm were repaired. Abdominal organ was not injured. She was discharged 14 days after the surgical procedure.

Changes in the Number of Gastrointestinal Cancers and Stage at Diagnosis with COVID-19 Pandemic in Japan: A Multicenter Cohort Study.

This retrospective cohort study compared the number of newly diagnosed patients, stage at diagnosis, and detection process of gastrointestinal cancers based on hospital-based cancer registry data at two tertiary Japanese hospitals. The pre-COVID-19 period was from January 2017 to February 2020, with phase 1 (midst of COVID-19 pandemic) from March to December 2020 and phase 2 (the transition period to the "new normal") from January to December 2021. Each month, the number of patients diagnosed with esophageal, gastric, colorectal, pancreatic, liver, and biliary tract cancers were aggregated, classified by stage and detection process, and compared, including a total of 6453 patients. The number of colorectal Stage 0-II patients decreased significantly in phase 1 and increased in phase 2. The total number of colorectal cancer patients returned to pre-COVID-19 levels (mean monthly patients [SD]: 41.61 [6.81] vs. 36.00 [6.72] vs. 46.00 [11.32]). The number of patients with gastric cancer Stage I significantly decreased in phase 2 following phase 1. The number of gastric cancer patients decreased significantly from pre-COVID-19 levels (30.63 [6.62] vs. 22.40 [5.85] vs. 24.50 [4.15]). During phase 2, the number of patients diagnosed after screening with colorectal cancer increased significantly, whereas that with gastric cancer remained considerably lower. The number of Stage III colorectal and gastric cancer patients increased significantly from the pre-COVID-19 levels. Thus, gastric cancer may not be optimally screened during phases 1 and 2. There was a significant increase in patients with Stage III colorectal and gastric cancers from the pre-COVID-19 period; hence, the stage at diagnosis may have progressed.

Clinicopathological features of endoscopically treated early gastric cancer with lymphovascular infiltration.

PURPOSE: Lymphovascular infiltration (LVI) may play a critical role in radicality and prognostic assessment of early gastric cancer (EGC). However, risk factors for LVI in endoscopically resected EGC remain unknown. This study evaluated the clinicopathological characteristics and prognoses of patients who underwent endoscopic resection of EGC to identify potential risk factors of LVI. METHODS: A cross-sectional study of patients who received gastric endoscopic submucosal dissection between February 1, 2012, and December 31, 2019, at two institutions was conducted. Among 1,462 lesions, 943 met the criteria for radical treatment considering features other than LVI and were included. The lesions were classified based on the presence of LVI. The clinicopathological characteristics of the two groups were compared. RESULTS: LVI was detected in 17 lesions (1.8%). The positivity rates of LVI were 0.7% (7/903) for intramucosal cancer and 25% (10/40) for submucosally invasive cancer. The LVI positivity rate was significantly higher for mixed-type cancer (lesions containing differentiated and undifferentiated-type carcinoma) than for non-mixed-type cancer (35.3 vs. 2.8%; P < 0.001) and for submucosally invasive cancer than for intramucosal cancer (58.8 vs. 3.2%; P < 0.001). In the multivariate logistic regression analysis, independent risk factors for LVI were mixed-type cancer (odds ratio; 95% confidence interval: 23.9; 5.0-115; P < 0.001) and submucosal invasion (58.7; 16.0-215; P < 0.001). CONCLUSIONS: Mixed-type cancer and submucosal invasion were risk factors for LVI in endoscopically resected EGC. These factors may play a critical role in the radicality and prognostic assessment of EGC.

Leukotriene Receptor Antagonist Therapy for the Chemoprevention of Human Rectal Aberrant Crypt Foci: Nonrandomized, Open-Label, Controlled Trial.

Leukotriene receptor antagonists (LTRA) are widely used drugs for treating allergic asthma, and they have recently been suggested to have a suppressive effect on carcinogenesis and cancer cell proliferation. Aberrant crypt foci (ACF) are considered a reliable surrogate biomarker of colorectal cancer. This prospective study explored the chemopreventive effect of an LTRA on colonic ACF formation and the safety of the medicine in patients as a pilot trial leading to a colorectal cancer chemoprevention trial.This was a nonrandomized, open-label, controlled trial in patients with colorectal ACFs. The participants were allocated to LTRA or observation groups. Patients in the LTRA group received 10 mg of montelukast orally daily for 8 weeks. After the intervention, colonoscopy was performed to evaluate the changes in the number of ACFs.From November 2017 to March 2020, 40 patients were enrolled. The first 30 were assigned to the LTRA group, and the remaining 10 were assigned to the observation group. In the LTRA group, the mean change in the number of ACFs per patient at 8 weeks from baseline was -2.4 ± 2.2, while the mean change in the observation group was 0.4 ± 2.3 (P = 0.002). There were no severe adverse events.This is the first study to explore the effect of LTRAs against colorectal ACF formation in humans. LTRAs are potential candidates for chemoprevention in colorectal cancer. PREVENTION RELEVANCE: We conducted the first LTRA chemoprevention trial for human rectal ACFs, which is considered a surrogate marker of colorectal carcinogenesis. 8-week treatment with LTRA suppressed ACF formation and cell proliferation in colonic epithelium. LTRAs are possible candidates for chemoprevention in colorectal cancer. See related Spotlight, p. 637.

Comparison of the diagnostic performance of NBI, Laser-BLI and LED-BLI: a randomized controlled noninferiority trial.

BACKGROUND AND AIMS: New image-enhanced endoscopy (IEE), blue Light Imaging (LED-BLI) is launched in USA and Europe, whereas Blue Laser Imaging (Laser-BLI) is available only Asian and some countries. No studies have directly compared the diagnostic accuracy of narrow band imaging (NBI), Laser-BLI and LED-BLI for colorectal tumors. The present study aimed to compare the diagnostic accuracy of the three methods for colorectal tumor using the NBI international colorectal endoscopic (NICE) classification and the Japanese NBI Expert Team (JNET) classifications. METHODS: This was a multi-center evaluator-blinded, randomized control trial of patients who underwent endoscopic colorectal tumor resection. The patients were randomly assigned to NBI, Laser-BLI or LED-BLI. Cropped images were sent to blinded external evaluators and diagnosed according to NICE and JNET classifications. The diagnostic accuracy of each endoscopy system was compared with non-inferiority test. RESULTS: A total of 619 colonic tumors were resected from 230 patients and evaluated by external four evaluators. The diagnostic accuracy of NBI for NICE 1, NICE 2, NICE 3 was 90.6%, 90.3% and 99.5%, respectively and for JNET 1, JNET 2A, JNET 2B and JNET 3, it was 94.6%, 72.0%, 79.2% and 99.1%, respectively. In non-inferiority test, Laser-BLI and LED-BLI revealed non-inferiority to NBI in all NICE and JNET categories (p<0.001). CONCLUSIONS: Laser-BLI and LED-BLI had high diagnostic accuracy and non-inferiority of NBI, especially for hyperplastic polyp/sessile serrated lesion and low-grade dysplasia. This is first trial to compare the diagnostic accuracy with NBI, Laser-BLI and LED-BLI and useful to understand the position of each IEE. This trial was registered as UMIN000032107.

Synthesis and evaluation of N-(4-benzylphenyl)piperazines as VGF inducers.

A series of compounds was discovered that induce the production of VGF mRNA in SH-SY5Y cells and exhibit cytoprotection under tunicamycin induced endoplasmic reticulum (ER) stress. The aminophenol ring and linker chain of the template SUN N8075 (1) was modified to yield compounds with higher efficacy and lower propensity for adverse effects.

The PDE10A inhibitor, papaverine, differentially activates ERK in male and female rat striatal slices.

The phosphodiesterase 10A (PDE10A) is highly expressed within dopaminoreceptive medium spiny neurons (MSNs) of the striatum, which are implicated in various neurodegenerative diseases and psychiatric disorders, such as Huntington's disease and schizophrenia. With its dual action on cAMP and cGMP, PDE10A has been proposed to affect several signaling cascades in the corticostriatothalamic circuits. In particular, papaverine, a selective PDE10A inhibitor has been shown to activate/phosphorylate ERK in striatum. We used acute rat striatal slices to further characterize the effects of papaverine on ERK activation/phosphorylation in D1- and D2-responsive striatal neurons. Incubation of striatal slices from male rats with papaverine increased the levels of phospho-ERK1/2 (p-ERK), an effect enhanced with a D1 agonist or a D2 antagonist, but decreased with a D1 receptor antagonist or a D2 receptor agonist. Papaverine-induced increase in p-ERK was localized in striatal neurons receiving D1-enriched presynaptic terminals, as well as in postsynaptic D2-enriched neurons in striatal slices. Interestingly, papaverine had almost no stimulatory effects on ERK1/2 phosphorylation in slices prepared from female rats. In striatal slices prepared from ovariectomized female rats, papaverine treatment stimulated ERK1/2 phosphorylation to levels similar to those in slices from male rats. Moreover, estrogen was found to regulate the levels of D2 but not D1 receptors in striatum. These results indicate that circulating levels of female hormones, and in particular estrogen, regulate the effects of PDE10A inhibition on ERK1/2 phosphorylation in medium spiny neurons, an effect possibly linked to estrogen's regulation of D2 receptors. Considering the variety of events modulated by ERK1/2 activity, these findings suggest that sex difference needs to be taken into consideration for the further investigation of the effects of PDE10A inhibitors.

An inducer of VGF protects cells against ER stress-induced cell death and prolongs survival in the mutant SOD1 animal models of familial ALS.

Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease, and recent evidence has suggested that endoplasmic reticulum (ER) stress signaling is involved in the pathogenesis of ALS. Here we identified a small molecule, SUN N8075, which has a marked protective effect on ER stress-induced cell death, in an in vitro cell-based screening, and its protective mechanism was mediated by an induction of VGF nerve growth factor inducible (VGF): VGF knockdown with siRNA completely abolished the protective effect of SUN N8075 against ER-induced cell death, and overexpression of VGF inhibited ER-stress-induced cell death. VGF level was lower in the spinal cords of sporadic ALS patients than in the control patients. Furthermore, SUN N8075 slowed disease progression and prolonged survival in mutant SOD1 transgenic mouse and rat models of ALS, preventing the decrease of VGF expression in the spinal cords of ALS mice. These data suggest that VGF plays a critical role in motor neuron survival and may be a potential new therapeutic target for ALS, and SUN N8075 may become a potential therapeutic candidate for treatment of ALS.