Transcriptome analysis reveals the essential role of NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) in gastric adenocarcinoma of fundic-gland type.

BACKGROUND: Gastric adenocarcinoma of fundic-gland type (GA-FG) is a gastric malignancy with little relation to Helicobacter pylori. Clinical characteristics of GA-FG have been established, but molecular mechanisms leading to tumorigenesis have not yet been elucidated. METHODS: We subjected three GA-FG tumors-normal mucosa pairs to microarray analysis. Network analysis was performed for the top 30 up-regulated gene transcripts, followed by immunohistochemical staining to confirm the gene expression analysis results. AGS and NUGC4 cells were transfected with the gene-encoding NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) to evaluate transcriptional changes in its target genes. RESULTS: Comprehensive gene expression analysis identified 1410 up-regulated and 1395 down-regulated gene probes with ≥ two-fold difference in expression. Among the top 30 up-regulated genes in GA-FG, we identified transcription factor NKX2-1/TTF-1, a master regulator of lung/thyroid differentiation, together with surfactant protein B (SFTPB), SFTPC, and secretoglobin family 3A member 2(SCGB3A2), which are regulated by NKX2-1/TTF-1. Immunohistochemical analysis of 16 GA-FG specimens demonstrated significantly higher NKX2-1/TTF-1 and SFTPB levels, as compared to that in adjacent normal mucosa (P < 0.05), while SCGB3A2 levels did not differ (P = 0.341). Transduction of NKX2-1/TTF-1 into AGS and NUGC4 cells induced transactivation of SFTPB and SFTPC, indicating that NKX2-1/TTF-1 can function as normally in gastric cells as it can in the lung cells. CONCLUSIONS: Our first transcriptome analysis of GA-FG indicates significant expression of NKX2-1/TTF1 in GA-FG. Immunohistochemistry and cell biology show ectopic expression and normal transactivation ability of NKX2-1/TTF-1, suggesting that it plays an essential role in GA-FG development.

The impact of sarcopenia on adverse events associated with gastric endoscopic submucosal dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) is one of the main methods of treatments for early gastric cancer. Sarcopenia is a known risk factor for postoperative adverse events; however, the effect of sarcopenia on gastric ESD is unclear. We investigated the impact of sarcopenia on short-term prognosis after gastric ESD. METHODS: This was a retrospective cohort study. We reviewed 832 patients who underwent gastric ESD between January 2015 and December 2019 and classified them into two groups: sarcopenia and non-sarcopenia groups. The curative resection rate, adverse events, and lengths of hospital stay were evaluated. We also evaluated risk factors associated with adverse events. RESULTS: 700 patients were analyzed (239 in the sarcopenia group and 461 in the non-sarcopenia group). The curative resection rates were similar in both groups. Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 (17% vs. 10%) were significantly more common, and the length of hospital stay was longer (8 vs. 7 days) in the sarcopenia group. Univariate analysis identified age ≥ 75 years, antithrombotic medication, history of gastric surgery, submucosal (SM) invasion, and sarcopenia as risk factors for CTCAE grade ≥ 2. Multivariate analysis showed that sarcopenia [odds ratio (OR) 1.79, 95% confidence interval (CI) 1.11-2.89, p = 0.016], history of gastric surgery (OR 9.32, 95% CI 1.97-44.05, p = 0.005), and SM invasion (OR 2.14, 95% CI 1.24-3.70, p = 0.006) were significant independent risk factors. CONCLUSIONS: Sarcopenia significantly affected short-term prognosis and is a novel risk factor for gastric ESD.

Pethidine dose and female sex as risk factors for nausea after esophagogastroduodenoscopy.

Nausea and vomiting after esophagogastroduodenoscopy have not been studied in detail. The aim of this study was to evaluate the risk factors for post-endoscopic nausea. We performed a case-control study at the Toyoshima Endoscopy Clinic. Eighteen patients with post-endoscopic nausea and 190 controls without post-endoscopic nausea were analyzed. We conducted univariate and multivariate logistic regression analyses with respect to patient age; sex; body height; body weight; the use of psychotropic drugs as baseline medications; and the dosing amounts of midazolam, pethidine, flumazenil and naloxone. On univariate analysis, post-endoscopic nausea was significantly related with patient age (odds ratio = 0.946); female sex (odds ratio = 10.85); body weight (odds ratio = 0.975); and the dose per kg body weight of pethidine (odds ratio = 53.03), naloxone (odds ratio = 1.676), and flumazenil (odds ratio = 1.26). On multivariate analysis, the dose per kg body weight of pethidine (odds ratio = 21.67, p = 0.004) and female sex (odds ratio = 13.12, p = 0.047) were the factors independently associated with post-endoscopic nausea. The prevalence of nausea after esophagogastroduodenoscopy was 0.49% (18/3,654). In conclusion, post-endoscopic nausea was associated with the dose of pethidine and female sex.

Premedication with fast-acting oxycodone hydrochloride hydrate effectively reduced oxaliplatin-induced severe vascular pain.

Oxaliplatin is a platinum-based chemotherapeutic agent that holds a prominent position in the treatment of colorectal and gastric cancers. However, severe oxaliplatin-related vascular pain can be problematic for patients. Here we describe seven patients who experienced severe vascular pain caused by oxaliplatin administration. All seven patients were treated with capecitabine and oxaliplatin or capecitabine plus oxaliplatin with bevacizumab as an adjuvant or a treatment for recurrent colorectal cancer, respectively. Patients experienced intolerable vascular pain during oxaliplatin administration, which continued for several days. Moreover, vascular pain also induced insomnia and appetite loss in all patients. We recommended implantation of a central venous (CV) port to the patients; however, all patients declined this treatment. In addition, various known countermeasures were taken, but were ineffective. Therefore, patients were orally administered oxycodone hydrochloride hydrate (Oxinorm®) 45 min prior to oxaliplatin administration. This pretreatment successfully reduced vascular pain and improved subsequent chemotherapy. Oxinorm® is a fast-acting opioid that can be an effective and practical option for severe vascular pain induced by oxaliplatin. The present report is the first description that emphasizes the usefulness of Oxinorm® to overcome the vascular pain induced by administration of oxaliplatin via a peripheral vein.

Electrosurgical knife with the water-jet function of tip-type during endoscopic treatment injection.

Objectives: This study aimed to objectively evaluate the water-jet-functioned electrosurgical knife injection performances in a desktop experiment. Methods: Five types of water-jet-functioned electrosurgical knives, including two injection styles of sheath-type (A: DualKnife J, KD-655L; B: FlushKnife, DK2620-J-B20S; C: Splash M-Knife, DN-D2718B; D: ISSEN, SN1650-20) and tip-type (E: ORISE ProKnife, M00519361) were evaluated. These knives were compared with an injection needle (Control: SuperGrip 25G) as a control. The injection speed under constant pressure and the injection efficiency for each knife against prepared porcine stomach mucosa were evaluated. The additional clear gel injections using an injection needle were observed using an indigo blue-colored gel to evaluate the difference between the locations of water-jet holes. Results: Four types of knives, except for A, showed significantly higher water-jet speeds (A: 0.79 ± 0.03 g/20 s, B: 2.56 ± 0.05 g/20 s, C: 3.09 ± 0.06 g/20 s, D: 2.86 ± 0.05 g/20 s, and E: 1.79 ± 0.03 g/20 s) compared to that of the control (1.21 ± 0.03 g/20 s). Meanwhile, significantly higher efficacy of injection was found in the tip-type water-jet function knife, second to the injection needle (Control: 37.2% ± 35.5%, A: 20.9% ± 20.2%, B: 1.1% ± 2.2%, C: 6.2% ± 12.6%, D: 12.5% ± 15.6%, and E: 33.3% ± 32.2%). An additional injection experiment revealed that the injection with a piercing tip into the gel could achieve sufficient additional injection inside the stacked clear gel. Conclusions: The tip-type water-jet function electrosurgical knife is preferable for effective submucosal injection during endoscopic treatments.

Long-term prognosis after endoscopic resection of T1a-MM/T1b-SM1 esophageal squamous cell carcinoma.

The objective of this study was to evaluate the long-term prognosis of T1a-MM/T1b-SM 1 esophageal squamous cell carcinoma (ESCC) after endoscopic resection (ER) and to validate the follow-up policy for pT1a-MM lymphovascular invasion (LVI)-negative ESCC. In this retrospective single-center analysis, patients who underwent ER for superficial ESCC between April 2002 and June 2021 were identified. The overall survival (OS), metastatic recurrence, and recurrence-free survival (RFS) rates were estimated using the Kaplan-Meier method. Cox proportional hazards models for OS, metastatic recurrence, and RFS were used. A total of 104 ESCC patients were eligible for the analysis. Of 104 patients, 81 had pT1a-MM, and 23 had pT1b-SM1. The 5-year OS, RFS, and metastatic recurrence rates of the 56 cases of pT1a-MM LVI-negative ESCC without additional treatment were 0.848 (95% confidence interval [CI]: 0.687-0.931), 0.817 (95% CI: 0.647-0.911), and 0.061 (95% CI: 0.014-0.240), respectively. Cox regression analysis for OS, RFS, and metastatic recurrence showed that only lymphatic invasion was strongly associated with metastatic recurrence (adjusted hazard ratio, 10.3; 95% CI: 2.01-53.3; P = .005). The proportion of deaths from other diseases was considerably higher (17/104, 16.3%) than that from ESCC (2/104, 1.9%). This may be related to the high complication rate of malignant tumors in other organs (43.3%, 45/104). The prognosis of ER for pT1a-MM and LVI-negative ESCC is good, and the follow-up policy is valid. Malignant tumors in other organs may be a major prognostic factor for superficial ESCC after ER.

Magnifying endoscopy with narrow-band imaging is useful in differentiating gastric cancer from matched adenoma in white light imaging.

This study assessed the effect of magnifying endoscopy with narrow-band imaging (M-NBI) on the endoscopic differential diagnosis between intramucosal gastric carcinomas and adenomas with matched characteristics. Associations between magnified endoscopic findings and pathological high-grade cellular and architectural atypia were also investigated. In total, the records of 50 adenomas and 50 intramucosal well-differentiated adenocarcinomas matched by tumor size (≥ 20 mm or < 20 mm), shape (depression or non-depression), and color (red or non-red) were extracted. Fourteen endoscopists diagnosed adenoma or cancer in the 100 cases with conventional white light imaging (C-WLI), then did the same with C-WLI + M-NBI.The cancer diagnostic sensitivity, specificity, and accuracy were assessed. The sensitivity of C-WLI + M-NBI for cancer diagnosis was 79.9% compared to 71.6% with C-WLI (p < 0.001). There were no significant differences in specificity (40.1% vs. 36.3%, p = 0.296) and accuracy (55.9% vs. 58.1%, p = 0.163). High-grade cytological or architectural atypia was diagnosed more often with irregular microvascular pattern (IMVP) or microsurface pattern (IMSP), respectively, than the low-grade forms. In conclusion, IMVP and IMSP correlate with high-grade cytological and architectural atypia. M-NBI is useful in differentiating intramucosal carcinoma from adenoma and can reduce underdiagnosis of cancer.

The natural history of sporadic non-ampullary duodenal epithelial tumors: Can we wait and see?

Objectives: The natural history of sporadic non-ampullary duodenal epithelial tumors (SNADETs) is poorly documented. The aim of this study was to evaluate the history of SNADETs in patients where immediate resection could not be performed. Methods: This is a single-center retrospective study of 86 consecutive cases of SNADETs who did not undergo immediate resection and were followed-up with upper gastrointestinal endoscopy for more than 6 months. Results: During a follow-up period of 36.8 (6.0-613.0) months, macroscopic progression was admitted in eight (9.3%). Of these, the final histology in four was adenocarcinoma, and three cases demonstrated submucosal invasion. Rates of macroscopic progression at 150 months after detection were 11.1%, 16.7%, and 30.0% for SNADETs <5 mm, <10 mm, and ≥10 mm, respectively. Conclusion: The overall risk of SNADETs progressing to invasive cancer is low. However, changes in macroscopic size or shape of SNADETs signify a high risk of progression to invasive cancer.

Colonoscopy using back brace support belt: A randomized, prospective trial.

BACKGROUND AND AIM: Looping is a major problem in colonoscopy, and it prolongs procedure time. We evaluated the efficacy and safety of an external abdominal compression device (back brace support belt; Maxbelt) with respect to cecal insertion time and other outcomes. METHODS: We performed a prospective study on outpatients undergoing elective colonoscopy in Toyoshima Endoscopy Clinic. Subjects were randomly assigned to groups and were subjected to either Maxbelt (n = 39) or no device (control, n = 38) during colonoscopy. The colonoscopist was blinded to the study. The primary outcome that was observed was insertion time. RESULTS: The intubation time of the Maxbelt group was shorter than that of the no device group, but the difference was not significant (3.29 vs 4.49 min, P = 0.069). After stratifying by age, the use of Maxbelt significantly decreased cecal intubation time in elderly participants (age ≥ 45) compared to no device group (3.27 vs 5.00 min, P = 0.032). The use of the Maxbelt significantly decreased insertion difficulty encountered by the colonoscopist (P = 0.01). There was no difference in adenoma detection rate, manual pressure, position change, and adverse event. CONCLUSIONS: The use of a back brace support belt could be a viable approach for colonoscopy in elderly patients. (University Hospital Medical Information Network: UMIN000029361).