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"Lefor, Alan Kawarai"
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Effectiveness and Safety of Vonoprazan versus Proton Pump Inhibitors for Second-Line Helicobacter pylori Eradication Therapy: Systematic Review and Meta-Analysis
Background: A novel potassium-competitive acid blocker, vonoprazan (VPZ), improves first-line Helicobacter pylori eradication success. The aim of this systematic review is to clarify the effectiveness and safety of second-line H. pylori eradication therapy comparing VPZ and proton pump inhibitor (PPI)-based regimens. Methods: Medline (PubMed), EMBASE, Web of Science, Cochrane Library, and the Japan Medical Abstract Society Database were searched. Results: We selected 16 studies for quantitative review. Forest plot analysis showed significant superiority of VPZ over PPI-based regimens in overall second-line H. pylori eradication success (OR 1.51, 95% CI 1.27–1.81, p < 0.001). Forest plots from 2 studies with propensity score matched analysis showed significant superiority of VPZ over PPI-based regimens (OR 3.09, 95% CI 1.71–5.58, p < 0.001). The remaining 14 studies with per-protocol analysis and the full analysis set also showed significant superiority (OR 1.40, 95% CI 1.16–1.69, p < 0.001). Regarding adverse events, Forest plot analysis did not show a significant difference between the 2 regimens (OR 0.88, 95% CI 0.58–1.32, p = 0.53). Conclusions: A VPZ-based regimen has significant superiority over a PPI-based regimen for second-line H. pylori eradication therapy. A VPZ-based second-line H. pylori eradication regimen can be the first choice.
Journal Article
Linked color imaging can enhance recognition of early gastric cancer by high color contrast to surrounding gastric intestinal metaplasia
2019
BackgroundLinked color imaging (LCI) increases the visibility of early gastric cancers, which may be associated with characteristic findings including background purple mucosae. These lesions are found in areas of chronic gastritis and surrounding mucosa. The aim of this study is to objectively characterize these lesions by color differences and color component values using LCI.MethodsFifty-two patients with early gastric cancer were enrolled. Color differences were calculated prospectively in malignant lesions and adjacent mucosa and compared with histological findings in resected specimens. Color component values of L*, a*, and b* were compared between purple and non-purple mucosae in areas of chronic gastritis. Based on histological findings, the accuracy of identifying gastric intestinal metaplasia was calculated.ResultsCancers and surrounding mucosa in 74% of lesions had similar colors using white light imaging (WLI), whereas purple mucosa surrounded part or all of cancers appearing orange–red, orange or orange–white using LCI. Greater color differences were seen using LCI compared to WLI, including flat-type cancers, leading to higher contrast. The surrounding purple mucosa corresponded histologically to intestinal metaplasia, facilitating the identification of malignant lesions. Forty lesions (83%) with purple mucosa and eight lesions (17%) with non-purple mucosa in areas of chronic gastritis were diagnosed as intestinal metaplasia by biopsy (83% accuracy). Color component values of purple mucosa differ significantly from those of non-purple mucosae.ConclusionsLCI images have higher color contrast between early gastric cancers and surrounding mucosa compared to WLI. A characteristic purple color around gastric cancers using LCI represents intestinal metaplasia.
Journal Article
Dopamine use and its consequences in the intensive care unit: a cohort study utilizing the Japanese Intensive care PAtient Database
by
Sanui, Masamitsu
,
Sasabuchi, Yusuke
,
Suzuki, Reina
in
Adolescent
,
Cardiovascular
,
Catecholamine
2022
Background
Dopamine is used to treat patients with shock in intensive care units (ICU) throughout the world, despite recent evidence against its use. The aim of this study was to identify the latest practice of dopamine use in Japan and also to explore the consequences of dopamine use in a large Asian population.
Methods
The Japanese Intensive Care PAtient Database (JIPAD), the largest intensive care database in Japan, was utilized. Inclusion criteria included: 1) age 18 years or older, 2) admitted to the ICU for reasons other than procedures, 3) ICU length of stay of 24 h or more, and 4) treatment with either dopamine or noradrenaline within 24 h of admission. The primary outcome was in-hospital mortality. Multivariable regression analysis was performed, followed by a propensity score-matched analysis.
Results
Of the 132,354 case records, 14,594 records from 56 facilities were included in this analysis. Dopamine was administered to 4,653 patients and noradrenaline to 11,844. There was no statistically significant difference in facility characteristics between frequent dopamine users (
N
= 28) and infrequent users (
N
= 28). Patients receiving dopamine had more cardiovascular diagnosis codes (70% vs. 42%;
p
< 0.01), more post-elective surgery status (60% vs. 31%), and lower APACHE III scores compared to patients given noradrenaline alone (70.7 vs. 83.0;
p
< 0.01). Multivariable analysis showed an odds ratio for in-hospital mortality of 0.86 [95% CI: 0.71–1.04] in the dopamine ≤ 5 μg/kg/min group, 1.46 [95% CI: 1.18–1.82] in the 5–15 μg/kg/min group, and 3.30 [95% CI: 1.19–9.19] in the > 15 μg/kg/min group. In a 1:1 propensity score matching for dopamine use as a vasopressor (570 pairs), both in-hospital mortality and ICU mortality were significantly higher in the dopamine group compared to no dopamine group (22.5% vs. 17.4%,
p
= 0.038; 13.3% vs. 8.8%,
p
= 0.018), as well as ICU length of stay (mean 9.3 days vs. 7.4 days,
p
= 0.004).
Conclusion
Dopamine is still widely used in Japan. The results of this study suggest detrimental effects of dopamine use specifically at a high dose.
Trial registration
Retrospectively registered upon approval of the Institutional Review Board and the administration office of JIPAD.
Journal Article
Minimally invasive esophagectomy and radical lymph node dissection without recurrent laryngeal nerve paralysis
by
Murakami Masahiko
,
Saito, Akira
,
Kohmoto Masahiro
in
Dissection
,
Endoscopy
,
Esophageal cancer
2020
BackgroundWe introduce a novel operative technique to dissect lymph nodes adjacent to the recurrent laryngeal nerve, referred to as the “native tissue preservation” technique. Using this technique, there was no damage to the recurrent laryngeal nerve, which is maintained in its anatomical position.MethodsFrom September 2016 to December 2018, minimally invasive esophagectomy was performed in the left lateral decubitus position in 87 patients with esophageal cancer. The native tissue preservation technique for lymphadenectomy around the recurrent laryngeal nerve was used, and all patients were evaluated for recurrent laryngeal nerve paralysis.ResultsMinimally invasive esophagectomy was completed in all patients without conversion to thoracotomy. Although an extended lymphadenectomy was performed in all patients, there were no grade II or higher complications (Clavien–Dindo classification) and no incidence of recurrent laryngeal nerve paralysis.ConclusionThe native tissue preservation technique may reduce the incidence of recurrent laryngeal nerve paralysis after minimally invasive esophagectomy with radical lymph node dissection.
Journal Article
Intraperitoneal transfer of microRNA‐29b‐containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer
2023
Small extracellular vesicles (sEV) contain various microRNAs (miRNAs) and play crucial roles in the tumor metastatic process. Although miR‐29b levels in peritoneal exosomes were markedly reduced in patients with peritoneal metastases (PM), their role has not been fully clarified. In this study, we asked whether the replacement of miR‐29b can affect the development of PM in a murine model. UE6E7T‐12, human bone marrow‐derived mesenchymal stem cells (BMSCs), were transfected with miR‐29b‐integrating recombinant lentiviral vector and sEV were isolated from culture supernatants using ultracentrifugation. The sEV contained markedly increased amounts of miR‐29b compared with negative controls. Treatment with transforming growth factor‐β1 decreased the expression of E‐cadherin and calretinin with increased expression of vimentin and fibronectin on human omental tissue‐derived mesothelial cells (HPMCs). However, the effects were totally abrogated by adding miR‐29b‐rich sEV. The sEV inhibited proliferation and migration of HPMCs by 15% (p < 0.005, n = 6) and 70% (p < 0.005, n = 6), respectively, and inhibited adhesion of NUGC‐4 and MKN45 to HPMCs by 90% (p < 0.0001, n = 5) and 77% (p < 0.0001, n = 5), respectively. MicroRNA‐29b‐rich murine sEV were similarly obtained using mouse BMSCs and examined for in vivo effects with a syngeneic murine model using YTN16P, a highly metastatic clone of gastric cancer cell. Intraperitoneal (IP) transfer of the sEV every 3 days markedly reduced the number of PM from YTN16P in the mesentery (p < 0.05, n = 6) and the omentum (p < 0.05, n = 6). Bone marrow mesenchymal stem cell‐derived sEV are a useful carrier for IP administration of miR‐29b, which can suppress the development of PM of gastric cancer. miR‐29b incorporated in mesenchymal stem cells (MSCs) derived exsosomes strongly inhibits mesothelial mesenchymal transition in vitro. Intraperitoneal transfer of the miR‐29b‐rich exosomes suppresses the development of peritoneal metastasis from gastric cancer in murine model.
Journal Article
Enteral free water vs. parenteral dextrose 5% in water for the treatment of hypernatremia in the intensive care unit: a retrospective cohort study from a mixed ICU
2023
Purpose
Effective treatment options for patients with hypernatremia are limited. Free water administration (parenterally or enterally) is the mainstay of treatment but the impact of each strategy on lowering serum sodium (Na) is not known. The purpose of the study was thus to assess the effectiveness of enteral free water vs. parenteral dextrose 5% in water (D5W) in treating ICU-acquired hypernatremia.
Methods
An electronic medical record-based, retrospective cohort study was conducted in a 30-bed mixed medical-surgical intensive care unit (ICU) in Japan. All adult patients admitted to the ICU from August 2017 to July 2021 were reviewed. After a 2-step exclusion, patients who stayed in the ICU ≥ 24 h and received either or both treatments for ICU-acquired hypernatremia (Na ≥ 145 mEq/L) constituted the study cohort. The primary outcome was a change in serum Na during the 24 h before treatment each day (ΔNa); the secondary outcomes were gastrointestinal complications, serum glucose levels, ICU/hospital mortality, ICU/hospital length of stay, and the duration of mechanical ventilation. Repeated measurements on each patient were addressed using a generalized estimated equation (GEE) for multiple linear regression analysis. Analysis was conducted with R version 4.0.3.
Results
In total, 256/6596 (131: D
5
W, 125: enteral free water) patients were analyzed. Median treatment lasted 6 days [3–17] for the D
5
W group vs 7 days [3–14] for the enteral free water group with a total median daily treatment volume of 799 [IQR 299–1221] mL vs. 400 [IQR 262–573] mL. GEE multiple linear regression analysis showed an estimated mean ΔNa per liter of treatment fluid of − 2.25 [95% CI − 2.76 to − 1.74] mEq/L per liter of parenteral D
5
W vs. − 1.91 mEq decrease [95% CI − 2.75 to − 1.07] per liter of enteral free water. Hydrochlorothiazide was the only medication associated with a statistically significant negative ΔNa by− 0.89 [− 1.57 to − 0.21] mEq/L. There were no significant inter-group differences for secondary outcomes.
Conclusions
These results suggest that both enteral free water and parenteral D
5
W are effective for treating ICU-acquired hypernatremia. Parenteral D
5
W was slightly more effective than enteral free water to lower serum Na levels in patients with ICU-acquired hypernatremia.
Trial registration
Not applicable.
Journal Article
Bowel habits and gender correlate with colon length measured by CT colonography
2022
PurposeCT colonography enables three-dimensional measurement of colon length. However, previous studies using CT colonography have not examined the association with gender, age, physique, a history of laparotomy and bowel habits, all possible contributory factors to colon length. The aim of this study is to investigate factors associated with colon length.Materials and methodsWe conducted a post hoc analysis based on data obtained from a previous multi-center trial including 321 patients with positive fecal immunochemical tests who underwent CT colonography. Colon length was measured using a computer-generated center line and was divided at the iliac crest level into the distal and proximal colons. Bowel habits were classified into three groups: A—daily; B—once every 2 or 3 days; and C—less than once in 3 days. Statistical comparison was made using one-way ANOVA with Bonferroni’s correction.ResultsA total of 295 patients were analyzed. The entire colon length (cm, mean ± standard deviation) of individual patients was 150.3 ± 18.5 cm and ranged from 109.7 to 195.9 cm. The female colon was significantly longer than the male colon (154.3 ± 18.1 cm vs. 147.1 ± 18.3 cm; p = 0.022). Colon length showed trends associated with age (p = 0.18) and a history of laparotomy (p = 0.14). According to bowel habits, the entire colon measured 147.4 ± 17.9 in group A, 154.7 ± 18.5 in group B and 158.6 ± 18.3 in group C, and significant differences were observed for “A vs. C” (p = 0.002) and “A vs. B” (p = 0.014). In subgroup analysis by colon segment, the proximal colon trended similarly to the entire colon while there were no trends for the distal colon.ConclusionsThis study has clearly demonstrated that bowel habits and gender both correlate with the length of the entire colon measured by CT colonography, and in particular, the proximal colon.Secondary abstractUsing CT colonography, we measured the colon length in 295 patients. The entire colon length was 150.3 ± 18.5 cm on average. Females and constipated (less frequent defecation) patients have a significantly longer colon, and in particular, the proximal colon. Colon length showed trends associated with age and a history of laparotomy.
Journal Article
Linked color imaging for the detection of early gastrointestinal neoplasms
by
Yamamoto, Hironori
,
Hayashi, Yoshikazu
,
Shinozaki, Satoshi
in
Endoscopy
,
Gastric cancer
,
Gastroenterology
2019
In routine upper and lower gastrointestinal endoscopy, overlooking neoplastic lesions is inevitable even for well-trained endoscopists. Various methods have been reported to improve the detection of gastrointestinal neoplasms including chromoendoscopy, special endoscopes, and processor and image enhanced technologies. Equipment-based image enhanced endoscopy (e-IEE) using narrow band imaging (NBI) and blue laser imaging (BLI) is useful to characterize known lesions with magnification at a close-up view. However, they are not useful for the early detection of superficial, pale neoplasms, or both because of the weak image at a distant view in a wide lumen such as the stomach or colon. Linked color imaging (LCI) is a novel pre- and post-processing technology developed by Fujifilm Corporation that has sufficient brightness to illuminate a wide lumen. LCI delineates early gastric cancers as orange–red and intestinal metaplasia as purple. LCI improves the adenoma detection rate in the colon and decreases the polyp miss rate. LCI contributes to the detection of superficial lesions throughout the gastrointestinal tract by enhancing the color contrast between the neoplasm and the surrounding mucosa. LCI can distinguish them by their specific color allocation based mainly on the distribution of capillaries. The authors believe that moving forward, LCI should be used in routine upper and lower gastrointestinal endoscopy.
Journal Article
Effect of Systemic or Intraperitoneal Administration of Anti-PD-1 Antibody for Peritoneal Metastases from Gastric Cancer
2022
Programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) blockade therapy is widely used for the treatment of patients with metastatic gastric cancer (GC). However, it is unclear how PD-1 antibodies affect the local immunity related to the growth of peritoneal metastases (PM). The clinical efficacy of PD-1/PD-L1 inhibitors against PM from GC has not been clearly determined.
We established a highly metastatic subclone of murine GC cells to the peritoneum, YTN16P, by in vivo selection and evaluated the effects of intravenous (IV) or intraperitoneal (IP) administration of anti-PD-1 antibody on PM in immunocompetent mice model. Phenotypes of immune cells in the spleen and peritoneal metastatic lesions were determined with flow cytometry and immunohistochemistry.
IP inoculation of YTN16P (1×10
) resulted in multiple mesenteric metastases after 3 weeks. IV and IP administration of anti-PD-1mAb reduced the number of metastases to the mesentery by 30~40% compared with isotype controls. However, no differences were observed depending on the route of administration. Although splenocyte phenotypes were not altered, the densities of CD8(+) T cells in peritoneal tumors were significantly increased, whereas those of Gr-1(+) myeloid derived suppressor cells (MDSC) were significantly reduced in mice treated with anti-PD-1 mAb.
PD-1 blockade therapy remodels the cellular immune composition of peritoneal tumors, which can partially suppress the PM from GC regardless of the route of administration. Adding anti-PD-1 antibody to chemotherapeutic regimens may enhance their anti-tumor effects against PM, which can lead to the prolongation of survival of patients with GC with peritoneal involvement.
Journal Article
Metformin combined with local irradiation provokes abscopal effects in a murine rectal cancer model
2022
Although preoperative chemoradiation therapy can down-stage locally advanced rectal cancer (LARC), it has little effect on distant metastases. Metformin exerts an anti-cancer effect partly through the activation of host immunity. LuM1, a highly lung metastatic subclone of colon 26, was injected subcutaneously (sc) in BALB/c mice and treated with metformin and/or local radiation (RT). Lung metastases and the primary tumors were evaluated and the phenotypes of immune cells in the spleen and lung metastases were examined with flow cytometry and immunohistochemistry. Local RT, but not metformin, partially delayed the growth of sc tumor which was augmented with metformin. Lung metastases were unchanged in metformin or RT alone, but significantly reduced in the combined therapy. The ratios of splenic T cells tended to be low in the RT group, which were increased by the addition of metformin. IFN-γ production of the splenic CD4(+) and CD8(+) T cells was enhanced and CD49b (+) CD335(+) activated NK cells was increased after combined treatment group. Density of NK cells infiltrating in lung metastases was increased after combination treatment. Metformin effectively enhances local and abscopal effects of RT though the activation of cell-mediated immunity and might be clinically useful for LARC.
Journal Article