Antinociceptive Effects of Intrathecal Landiolol Injection in a Rat Formalin Pain Model

Perioperative beta-blocker administration has recently been recommended for patients undergoing cardiac or other surgery due to the beneficial cardiovascular effects of these agents. In addition, some studies have reported that perioperatively administered beta-blockers also have analgesic effects. In this study, to investigate the antinociceptive effects and the analgesic profile of landiolol, we examined the effects of intrathecal landiolol administration on nociceptive pain behavior and c-fos mRNA expression (a neural marker of pain) in the spinal cord using a rat formalin model. We found that pain-related behavior was inhibited by intrathecal landiolol administration. Moreover, the increase in c-fos mRNA expression on the formalin-injected side was less pronounced in rats administered landiolol than in saline administered controls. Thus, intrathecal administration of landiolol exhibited antinociceptive effects. Further investigation of the antinociceptive mechanism of landiolol is required

Reality of Gastric Cancer in Young Patients: The Importance and Difficulty of the Early Diagnosis, Prevention and Treatment

Gastric cancer usually arises in middle-aged to older patients, and is rarely found in younger patients. The clin-ical characteristics, etiology, prognosis, preventive methods and treatment of gastric cancer in young patients have not been fully investigated because of its low prevalence. In this review, we discuss the current under-standing and clinical problems associated with gastric cancer in young patients. Helicobacter pylori (H. pylori), which is a major cause of gastric cancer, especially in older populations, is closely associated with gastric cancer in young patients as well as in older patients. Gastric cancer in young patients tends to be diagnosed at an advanced stage with alarm symptoms. However, young patients with advanced gastric cancer tend to have a favorable general condition and organ function, so they can tolerate intensive systematic chemotherapy. Unfortunately, the prognosis of gastric cancer in young patients with an advanced stage is not favorable. We should not take this rare disease lightly, given its poor prognosis if patients are diagnosed at an unresectable stage. The evaluation of the H. pylori infection status and performance of H. pylori eradication therapy to prevent gastric cancer in young patients as well as the development of more intensive chemotherapy regimens for unre-sectable gastric cancer in young patients are warranted

Nivolumab-induced IgA nephropathy in a patient with advanced gastric cancer A case report

Introduction: Immune checkpoint inhibitors including nivolumab, an antibody against programmed death-1, have been increasingly introduced in various cancer treatment regimens, and are reported to be associated with immune-related adverse events. Nivolumab-induced renal injury is generally caused by acute interstitial nephritis and is managed by drug discontinuation and steroid therapy. Although this agent can infrequently induce glomerulonephritis, the pathogenesis and therapeutic strategy remain undetermined. Patient concerns: A 78-year-old man was diagnosed with advanced gastric cancer with portal thrombosis. First- and second-line chemotherapies were ineffective; thus, nivolumab monotherapy was initiated. Although it effectively prevented tumor growth, proteinuria and microhematuria appeared 2 months later. Despite drug discontinuation, serum creatinine progressively increased from 0.72 to 1.45 mg/dL. Renal biopsy revealed mesangial IgA and C3 deposition in immunofluorescence analysis and mesangial proliferation with crescent formation in light microscopy. Diagnosis: The patient was diagnosed with IgA nephropathy. Based on the temporal relationship between the nivolumab therapy and abnormal urinalysis, IgA nephropathy was considered to have been induced by nivolumab. Interventions: A moderate dose (0.6 mg/kg/day) of prednisolone was orally administrated, with tapering biweekly. Outcomes: Steroid therapy stabilized his serum creatinine levels and markedly reduced proteinuria. However, bacterial pneumonia substantially impaired his performance status; thus, nivolumab could not be restarted despite tumor regrowth. Lessons: IgA nephropathy should be recognized as an uncommon renal adverse event during nivolumab therapy. After drug discontinuation, nivolumab-induced IgA nephropathy is likely to respond to moderate doses of steroid therapy with early tapering. However, more evidence is needed to determine whether nivolumab can be safely restarted during or after steroid therapy

Newly Designed Specula for Laryngomicroscopy

We produced specula for laryngomicroscopy to observe blind spots in the operating field. Use of these specula has facilitated detailed observation of the lower surface of the false vocal folds, laryngeal ventricle, and subglottis, which were previously in blind spots. The specula are useful in the following ways: 1) clarifying blind spots for improved diagnosis and providing more accurate surgical margins; 2) observing the lower lips of the vocal folds in phonosurgery; and 3) Vaporizing with laser reflection. The specula are cheap and easy to use and are well worth considering for application to laryngomicroscopy

Site-specific differences in T lymphocyte composition of the gastric mucosa after Helicobacter pylori eradication

In our earlier work, we revealed that inflammation of the lesser curvature of the gastric body and antrum could constitute independent risk factors for gastric cancer development, while inflammation of the greater curvature was not. The aims of this study were as follows: first, to reveal the differences between T lymphocyte populations of the gastric antrum and the greater and lesser curvatures of the gastric body in patients after Helicobacter pylori eradication; second, to analyze the correlation between the composition of the stomach-resident T lymphocytes and time from H. pylori eradication; and third, to evaluate the sex differences in T lymphocyte subsets after H. pylori eradication. To investigate site-specific differences in stomach-resident T lymphocytes after H. pylori eradication, we performed flow cytometry analysis on samples taken from the gastric antrum, greater curvature of the gastric body, and lesser curvature of the gastric body of 20 patients. We also analyzed the correlation between the composition of the stomach-resident T lymphocytes and the time from H. pylori eradication. The lymphocyte subsets of the antrum and lesser curvature of the body were similar. In contrast, compared to those in the greater curvature of the gastric body, CD4(+)/CD3(+) lymphocyte subsets (43.8 +/- 19.4% vs 31.7 +/- 14.6%) were elevated in the lesser curvature of the body, whereas CD8(+)/CD3(+) (67.1 +/- 21.3% vs 80.4 +/- 12.0%), CD7(+)/CD3(+) (91.2 +/- 4.6% vs 93.7 +/- 3.8%), CCR4(+)/CD3(+) (7.7 +/- 8.1% vs 10.4 +/- 7.0%), CD45RA(+)/CD3(+)CD4(+) (27.2 +/- 24.8% vs 39.5 +/- 20.8%), and CD45RA(+)/CD3(+)CD4(-) (14.2 +/- 11.1% vs 18.7 +/- 11.5) were lower. Linear regression analysis showed a negative correlation between the time after H. pylori eradication and CD4(+)/CD3(+) (P < .05, R-2 = 0.198). There were no significant differences between men and women with respect to the lymphocyte populations. These results indicate that there are site-specific differences in lymphocyte composition in the stomach after H. pylori eradication

Scoring systems for differentiating gastrointestinal stromal tumors and schwannomas from leiomyomas in the stomach

There is no practical predictive model for the diagnosis of gastrointestinal stromal tumors (GISTs). To establish a practical predictive model for the diagnosis of subepithelial lesions in the stomach, we reviewed patients with GISTs (n = 89), schwannomas (n = 7), and leiomyomas (n = 28). The tumor was more frequently found along the gastric cardia in the leiomyoma group (57.1%) than in the GIST/schwannoma group (2.1%, P < .01). Contrast enhancement (57.3% vs 0%, P < .01) and intra-tumoral necrosis (34.4% vs 0.0%, P < .01) were more frequently observed in the GIST/schwannoma group than in the leiomyoma group. On endoscopic ultrasonography, 58.3% of GISTs/schwannomas showed uneven echogenicity, whereas the echogenicity was uneven in 21.4% of leiomyomas (P < .01). There were no differences between the tumor color and the presence or absence of ulcer formation, tumor bleeding, irregularity of the tumor margin, cystic spaces, and hyperechoic spots between the 2 groups. Based on these results, we developed a 2-step diagnostic algorithm for GISTs/schwannomas. The first step comprises 1 endoscopic feature: a cardiac or non-cardiac location. Tumors with a cardiac location were judged as leiomyomas and those with a non-cardiac location were judged as GISTs/schwannomas, with 96.9% sensitivity and 57.1% specificity for GIST/schwannoma diagnosis. The second step comprises a combination of endoscopic (non-cardiac location), radiologic (positive contrast enhancement and intra-tumoral necrosis), and endosonographic (uneven echogenicity) features for a total of 4 points. We assigned 1 point to each feature. Tumors with scores of 2 to 4 were judged as GISTs/schwannomas, with 81.3% sensitivity and 92.9% specificity for GIST/schwannoma diagnosis. Our predictive model will be a practical guide for the management of gastric subepithelial lesions

Endocrinological Changes after Anamorelin Administration in Patients with Gastrointestinal Cancer

Changes in hormone levels in patients with cancer cachexia after anamorelin administration have not been fully investigated. This study aimed to determine how anamorelin affects the endocrine system in patients with gastrointestinal cancer and cachexia. We prospectively enrolled 13 patients and comprehensively investigated their body weight and levels of serum albumin, hemoglobin A1c (HbA1c), and hormones before (week 0) and 3 and 12 weeks after anamorelin administration. The variables were evaluated at week 3 in 9 patients and at week 12 in 5 patients. At week 3, anamorelin administration resulted in body weight gain and increased the levels of growth hormone and HbA1c, as well as insulin-like growth factor-1 standard deviation scores (IGF-1 SD scores). At the same time, negative correlations were observed between ΔIGF-1 SD score and Δthyroidstimulating hormone (TSH) and between ΔIGF-1 SD score and Δfree testosterone. ΔBody weight and ΔIGF-1 SD score correlated positively at week 12. These results suggest that TSH and free testosterone levels can be affected 3 weeks after anamorelin administration; however, those variables tend to return to a state of equilibrium, and anabolic effects of anamorelin appear in long-term (≥ 12 weeks) users

The Impact of KRAS Mutation in Patients With Sporadic Nonampullary Duodenal Epithelial Tumors

INTRODUCTION: The genomic characterization of primary nonampullary duodenal adenocarcinoma indicates a genetic resemblance to gastric and colorectal cancers. However, a correlation between the clinical and molecular characteristics of these cancers has not been established. This study aimed to elucidate the clinicopathological features of sporadic nonampullary duodenal epithelial tumors, including their molecular characteristics and prognostic factors. METHODS: One hundred forty-eight patients with sporadic nonampullary duodenal epithelial tumors were examined in this study. Patient sex, age, TNM stage, tumor location, treatment methods, histology, KRAS mutation, BRAF mutation, Fusobacterium nucleatum, mucin phenotype, and programmed death-ligand 1 (PD-L1) status were evaluated. KRAS and BRAF mutations, Fusobacterium nucleatum, mucin phenotype, and PD-L1 status were analyzed by direct sequencing, quantitative polymerase chain reaction, and immunochemical staining. RESULTS: The median follow-up duration was 119.4 months. There were no deaths from duodenal adenoma (the primary disease). Kaplan-Meier analysis for duodenal adenocarcinoma showed a significant effect of TNM stage (P DISCUSSION: Only KRAS mutation was a significant prognostic factor in primary sporadic nonampullary duodenal adenocarcinoma in cases in which TNM stage was considered