Predictors of technical difficulty for trainees in esophageal endoscopic submucosal dissection.

BACKGROUND: Esophageal endoscopic submucosal dissection (ESD) is technically challenging, especially for trainees, and requires a safe training system. This study aimed to identify predictors of technical difficulty facing trainees performing esophageal ESD to establish such system. METHODS: This was a single-center retrospective study of patients with esophageal cancer who underwent ESD performed by trainees between January 2010 and August 2022. Technical difficulties were defined as muscularis propria exposure and long procedure time (≥ 90 min). Factors associated with these technical difficulties were investigated. RESULTS: A total of 798 lesions in 721 patients were evaluated. Muscularis propria exposure occurred in 298 lesions (37.3%), including 10 perforations (1.3%). The procedure time was ≥ 90 min in 134 lesions (16.8%). In the multivariate analysis, tumor size ≥ 20 mm, tumors ≥ 1/2 of the circumference, and those close to previous treatment scars significantly increased the incidence of both difficulties, whereas tumors in the upper esophagus significantly decreased this incidence. Furthermore, female sex and tumors in the left wall were independent predictors of muscularis propria exposure, and elevated morphology was an independent predictor of long procedure time. Muscularis propria exposure and long procedure time occurred in more than half of the cases with three or more predictors of each difficulty. CONCLUSIONS: Large tumors and tumors close to previous treatment scars increase technical difficulties for trainees in esophageal ESD. Conversely, tumors in the upper esophagus reduce these difficulties. These results enable us to predict the difficulty level preoperatively and select appropriate cases in stepwise training.

A case of pyloric gland adenoma with high-grade dysplasia in the duodenum arising from heterotopic gastric mucosa observed over 5 years.

Pyloric gland adenoma (PGA) in the duodenum is a rare gastric phenotype duodenal neoplasm. Although heterotopic gastric mucosa in the duodenum has been recognized as a benign lesion, it is a potential precursor of PGA and gastric phenotype adenocarcinoma. Herein, we present a case follow-up of endoscopic and histological changes in the PGA in the duodenum from low-grade to high-grade dysplasia. PGA was considered to arise from the heterotopic gastric mucosa, because the heterotopic gastric mucosa was observed in the initial examination. It is difficult to distinguish heterotopic gastric mucosa from PGAs, both endoscopically and histologically. This increase in size may be useful for their differentiation. Therefore, endoscopists should not underestimate the growth of the heterotopic gastric mucosa compared to that in the previous examination.

Lustrous White Erosions Surrounded by an Erythematous Mucosa: A Novel Endoscopic Finding of Gastric Lesions in Patients with Wilson Disease.

Wilson disease is an inherited copper metabolism disorder. We herein report a novel endoscopic finding in three men with Wilson disease. These patients underwent upper endoscopy due to gastrointestinal symptoms or during follow-up. In each case, endoscopy revealed lustrous white erosions surrounded by an erythematous mucosa in the greater curvature of the gastric body. A biopsy of the lesions showed orcein-positive tissue, indicating copper deposition, in the interstitial stroma and fundic glands of the mucosa. All patients had been receiving treatment with zinc acetate. These endoscopic findings might have been related to the cytotoxicity of the accumulated copper and zinc acetate.

Efficacy of Ninjin'yoeito in treating severe coronavirus disease 2019 in patients in an intensive care unit.

Coronavirus Disease-2019 (COVID-19), an infectious disease associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global emergency with high mortality. There are few effective treatments, and many severe patients are treated in an intensive care unit (ICU). The purpose of this study was to evaluate whether the Japanese Kampo medicine ninjin'yoeito (NYT) is effective in treating ICU patients with COVID-19. Nine patients with confirmed SARS-CoV-2 infection admitted to the ICU were enrolled in this study. All patients underwent respiratory management with invasive mechanical ventilation (IMV) and enteral nutrition. Four patients received NYT (7.5 g daily) from an elemental diet tube. We retrospectively examined the prognostic nutritional index (PNI), length of IMV, length of ICU stay, length of hospital stay, rate of tracheostomy, and mortality rate. The median age of the enrolled participants was 60.0 years (4 men and 5 women). The median body mass index was 27.6. The most common comorbidity was diabetes (4 patients, 44%), followed by hypertension (3 patients, 33%) and chronic kidney disease (2 patients, 22%). The median length of IMV, ICU stay, and hospital stay were all shorter in the NYT group than in the non-NYT group (IMV; 4.0 days vs 14.3 days, ICU; 5.3 days vs 14.5 days, hospital stay; 19.9 days vs 28.2 days). In the NYT and non-NYT groups, the median PNI at admission was 29.0 and 31.2, respectively. One week after admission, the PNI was 30.7 in the NYT group and 24.4 in non-NYT group. PNI was significantly (p = 0.032) increased in the NYT group (+13.6%) than in the non-NYT group (-22.0%). The Japanese Kampo medicine NYT might be useful for treating patients with severe COVID-19 in ICU. This study was conducted in a small number of cases, and further large clinical trials are necessary.

Erratum: Ex vivo induction of antitumor DEC-205+ CD11c+ cells in a murine neuroblastoma model by co-stimulation with doxorubicin, lipopolysaccharide and interleukin-4.

[This corrects the article DOI: 10.3892/br.2015.546.].

Chemoimmunotherapeutic effect of combined treatment with ex vivo generated antigen-presenting immune cells and conventional antitumor agents in a mouse neuroblastoma model.

PURPOSE: Combining antitumor immunotherapy with conventional intensive multimodal therapy may be considered for advanced neuroblastoma. We investigated combination therapy with ex vivo generated immunostimulatory cells and intraperitoneal doxorubicin. METHODS: Immunogenic death of neuro-2a neuroblastoma cells was induced by doxorubicin or cisplatin (negative control). Mouse bone marrow cells were cultured with granulocyte-macrophage colony-stimulating factor, followed by addition of doxorubicin-killed neuro-2a cells with or without interleukin-4 and/or CpG-oligodeoxynucleotide to induce immunostimulatory cells. CD8α+ lymphocytes were cocultured with killed neuro-2a cells and immunostimulatory cells, and interferon-γ was measured in the supernatant. Furthermore, female A/J mice were injected with viable neuro-2a cells, followed by immunostimulatory cells and doxorubicin. Then intraabdominal tumor nodules were evaluated. RESULTS: Bone marrow-derived immunostimulatory cells only promoted interferon-γ production by CD8α+ lymphocytes after first being stimulated by doxorubicin-killed neuro-2a cells and interleukin-4, followed by CpG-oligodeoxynucleotide. These cells had a surface antigen expression profile compatible with activated dendritic cells and suppressed tumors in mice intravenously injected with neuro-2a cells. Despite a similar surface antigen profile, the in vivo antitumor effect was stronger after injection of immunostimulatory cells induced by doxorubicin-killed neuro-2a cells compared with cells induced by cisplatin-killed neuro-2a cells. Moreover, interferon-γ production was greater when CD8α+ lymphocytes were cocultured with doxorubicin-killed neuro-2a cells and immunostimulatory cells rather than with cisplatin-killed cells. CONCLUSION: Cells with antitumor activity can be induced from bone marrow cells. Combining such cells with doxorubicin may activate antitumor immunity in tumor-bearing mice. Interactions between induced immunostimulatory cells and conventional chemotherapy might be important for antitumor immunity.

Acute gastric volvulus associated with wandering spleen in an adult treated laparoscopically after endoscopic reduction: a case report.

A 43-year-old female was referred to our hospital for sudden onset of abdominal pain, fullness, and vomiting. Physical examination revealed abdominal distension with mild epigastric tenderness. Abdominal radiography showed massive gastric distension and plain computed tomography (CT) a markedly enlarged stomach filled with gas and fluid. A large volume of gastric contents was suctioned out via a nasogastric (NG) tube. Contrast-enhanced CT showed a grossly distended stomach with displacement of the antrum above the gastroesophageal junction, and the spleen was dislocated inferiorly. Upper gastrointestinal (GI) series showed the greater curvature to be elevated and the gastric fundus to be lower than normal. Acute mesenteroaxial gastric volvulus was diagnosed. GI endoscopy showed a distortion of the gastric anatomy with difficulty intubating the pylorus. Various endoscopic maneuvers were required to reposition the stomach, and the symptoms showed immediate and complete solution. GI fluoroscopy was performed 3 days later. Initially, most of the contrast medium accumulated in the fundus, which was drawn prominently downward, and then began flowing into the duodenum with anteflexion. Elective laparoscopic surgery was performed 1 month later. The stomach was in its normal position, but the fundus was folded posteroinferiorly. The spleen attached to the fundus was normal in size but extremely mobile. We diagnosed a wandering spleen based on the operative findings. Gastropexy was performed for the treatment of gastric volvulus and wandering spleen. The patient remained asymptomatic, and there was no evidence of recurrence during a follow-up period of 24 months. This report describes a rare adult case of acute gastric volvulus associated with wandering spleen. Because delay in treatment can result in lethal complications, it is critical to provide a prompt and correct diagnosis and surgical intervention. We advocate laparoscopic surgery after endoscopic reduction because it is a safe and effective procedure with lower invasiveness.

Ex vivo induction of antitumor DEC-205+ CD11c+ cells in a murine neuroblastoma model by co-stimulation with doxorubicin, lipopolysaccharide and interleukin-4.

The antigen-presenting capacity of specific cells and tumor immunogenicity involved in innate cellular immunity are important for initiating an antitumor response to advanced neuroblastoma. The present study was performed to establish a method of producing antigen-presenting cells that induced an immune response to murine neuroblastoma cells through culture with neuroblastoma cells that had undergone immunogenic cell death. Immunogenic death of neuro-2a murine neuroblastoma cells was induced by exposure to doxorubicin. Mouse bone marrow cells were cultured in medium containing granulocyte-macrophage colony-stimulating factor, followed by the addition of doxorubicin-treated neuro-2a cells to the culture with or without lipopolysaccharide (LPS) and/or interleukin-4. Subsequently, cluster of differentiation (CD) 8α+ lymphocytes were co-cultured with neuro-2a cells and the adherent bone marrow cells obtained by the above procedure to evaluate CD8α+ lymphocyte proliferation and interferon-γ production. Furthermore, the surface antigen profile of adherent bone marrow cells was analyzed by flow cytometry. When adherent bone marrow cells were treated with LPS and/or interleukin-4, followed by co-culture with CD8α+ lymphocytes and neuro-2a cells, interferon-γ production by the CD8α+ cells increased in response to anti-CD3/CD28 antibody stimulation. CD11c major histocompatibility complex II (MHC II) double-positive cells were increased among adherent cells derived from cultured bone marrow cells. These cells were positive for DEC-205, but not CD8α. These findings suggest that co-culture of bone marrow-derived cells with tumor cells (that have undergone immunogenic death by exposure to doxorubicin) plus stimulation by LPS and interleukin-4 induces antigen-presenting cells that can evoke an immune response to neuroblastoma. Bone marrow-derived DEC-205+ CD11c+ MHC II+ dendritic cells are key antigen-presenting cells in the induction of an immune response following phagocytosis of doxorubicin-treated neuroblastoma cells.