Search

Abstract A novel concept of Metabolic Associated Fatty Liver Disease (MAFLD) was proposed, incorporating metabolic abnormalities such as obesity and diabetes, which are risk factors that affect the prognosis. Non-Alcoholic Fatty Liver Disease (NAFLD), entails fat accumulation in the liver without alcohol consumption and is often linked to obesity, insulin resistance, and metabolic syndrome. However, the broad nature of the disease concept has hindered prognosis accuracy. In this study, we assess the contribution of the impact of diagnostic criteria for MAFLD on metabolic disease progression compared to conventional diagnostic criteria for NAFLD. A total of 7159 patient who were presented to the health screening center in Tokai University Hospital both in 2015 and 2020 were included in the study. Fatty liver was diagnosed using abdominal ultrasonography. The diagnostic criteria for NAFLD were consistent with the global guidelines based on alcohol consumption. The diagnostic criteria for MAFLD were based on the International Consensus Panel. Medications (anti-hypertensive, diabetic, and dyslipidemia medications) were evaluated by self-administration in the submitted medical questionnaire. A total of 2500 (34.9%) participants were diagnosed with fatty liver (FL +), 1811 (72.4%) fit both NAFLD and MAFLD diagnostic criteria (overlap), 230 (9.2%) fit only the NAFLD diagnostic criteria (NAFLD group) and 404 (16.1%) fit the MAFLD diagnostic criteria (MAFLD group) at 2015. Over the next 5 years, medication rates increased in the NAFLD group for anti-hypertensive, + 17 (7.4%); diabetes, + 3 (1.3%); and dyslipidemia, + 32 (13.9%). In contrast, the only-MAFLD group showed a more significant increase with + 49 (12.1%), + 21 (5.2%), and + 49 (12.1%), for the respective medications, indicating a substantial rise in patients starting new medications. Our analysis of repeated health check-ups on participants revealed that the diagnostic criteria for MAFLD are more predictive of future treatment for metabolic disease than conventional diagnostic criteria for NAFLD.

The International Rome Committee defines Disorders of Gut-Brain Interactions (DGBI) based upon distinct combinations of chronic and/or recurrent unexplained gastrointestinal symptoms. Yet patients often experience overlapping DGBI. Patients with DGBI frequently also suffer from extraintestinal symptoms, including fatigue, sleep disturbances, anxiety, and depression. Patients with overlapping DGBI typically experience more severe GI symptoms and increased psychosocial burden. Concerning the pathophysiology, DGBI are associated with disruptions in gut motility, function of the brain and enteric neurons, immune function, and genetic markers, with recent findings revealing gut microbiome alterations linked to these mechanisms of DGBI. Emerging evidence summarized in this review suggests that the microbiome influences various established disease mechanisms of different DGBI groups. Overall, changes in the gastrointestinal microbiome do not seem to be linked to a specific DGBI subgroup but may play a key role in the manifestation of different DGBI and, subsequently, overlap of DGBI. Understanding these shared mechanisms and the role of the gastrointestinal microbiome, particularly for overlapping DGBI, might aid in developing more precise diagnostic criteria and treatment strategies while developing personalized interventions that target specific mechanisms to improve patient outcomes.

Abstract Background The purpose of this study was to compare the dosimetric characteristics of five different treatment planning techniques for locally advanced non‐small cell lung cancer (LA‐NSCLC) with sequential plan changes. Methods A total of 13 stage III NSCLC patients were enrolled in this study. These patients had both computed tomography (CT) images for initial and boost treatment plans. The latter CT images were taken if tumor shrinkage was observed after 2 weeks of treatment. The prescription dose was 60 Gy/30 Fr (initial: 40 Gy/20 Fr, and boost: 20 Gy/10 Fr). Five techniques (forward‐planed 3‐dimensional conformal radiotherapy [F‐3DCRT] on both CT images, inverse‐planned 3DCRT [I‐3DCRT] on both CT images, volumetric modulated arc therapy [VMAT] on both CT images, F‐3DCRT on initial CT plus VMAT on boost CT [bVMAT], and hybrid of fixed intensity‐modulated radiotherapy [IMRT] beams and VMAT beams on both CT images [hybrid]) were recalculated for all patients. The accumulated doses between initial and boost plans were compared among all treatment techniques. Results The conformity indexes (CI) of the planning target volume (PTV) of the five planning techniques were 0.34 ± 0.10, 0.57 ± 0.10, 0.86 ± 0.08, 0.61 ± 0.12, and 0.83 ± 0.11 for F‐3DCRT, I‐3DCRT, VMAT, bVMAT, and hybrid, respectively. In the same manner, lung volumes receiving >20 Gy (V20Gy) were 21.05 ± 10.56%, 20.86 ± 6.45, 19.50 ± 7.38%, 19.98 ± 10.04%, and 17.74 ± 7.86%. There was significant improvement about CI and V20Gy for hybrid compared with F‐3DCRT (p

Background CyberKnife treatment for central lung tumors and mediastinal tumors can be difficult to perform with marker less. Purpose We aimed to evaluate a novel tracheobronchial-based method (ie, tracheobronchial tracking) for the purpose of minimally invasive CyberKnife treatment for central lung and mediastinal tumors. Methods Five verification plans were created using an in-house phantom. Each plan included five irradiation sessions. The reference plan irradiated and tracked the simulated tumor (using the target tracking volume, TTV). Trachea plans tracked the simulated tracheo-bronchus and irradiated the simulated tumor and included two types of subplans: correlated plans in which the displacement of the simulated tracheobronchial and the simulated tumor were correlated, and non-correlated plans in which these factors were not correlated. Moreover, 15 mm and 25 mm TTVs were evaluated for each plan. The sin waveform and the patient's respiratory waveform were prepared as the respiratory model. Evaluations were performed by calculating the dose difference between the radiophotoluminescent glass dosimeter (RPLD)-generated mean dose values (generated by the treatment planning system, TPS) and the actual absorbed RPLD dose. Statistical analyses were performed to evaluate findings for each plan. Correlation and prediction errors were calculated for each axis of each plan using log files to evaluate tracking accuracy. Results Dose differences were statistically significant only in comparisons with the non-correlated plan. When evaluated using the sin waveform, the mean values for correlation and prediction errors in each axis and for all plans were less than 0.6 mm and 0.1 mm, respectively. In the same manner, they were less than 1.1 mm and 0.2 mm when evaluated using the patient's respiratory waveform. Conclusion Our newly-developed tracheobronchial tracking method would be useful in facilitating minimally invasive CyberKnife treatment in certain cases of central lung and mediastinal tumors.

Summary: Infection with Helicobacter suis, which causes many cases of gastric disease, is not reliably diagnosed. Here, we present a protocol for detecting H. suis infection. We describe steps for collecting gastric biopsies and sera from patients, preparing DNA for PCR, and targeting the H. suis-specific gene. We then define procedures for inoculating biopsies onto primary agar plates and transferring colonies to secondary agar plates. Finally, we detail whole-genome sequencing of bacteria and assess H. suis infection in sera with ELISA.For complete details on the use and execution of these protocols, please refer to Matsui et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background and aim The severity of atrophic gastritis is significantly associated with the risk of gastric cancer. Although the current gold standard for assessing the gastric cancer risk is esophagogastroduodenoscopy with a pathological examination, the development of less-invasive biomarkers is warranted for efficient risk stratification of gastric cancer. Serum pepsinogens (PGs) are biomarkers used to predict the extent of gastric mucosal atrophy; however, they are not an accurate reflection of gastric mucosal atrophy after Helicobacter pylori eradication. The present study was conducted to investigate the usefulness of plasma ghrelin levels as a marker for gastric mucosal atrophy, and as a risk stratification marker for gastric cancer, even after H. pylori eradication. Methods Patients who received H. pylori eradication treatment were enrolled in the study. The severity of gastric mucosal atrophy was evaluated both endoscopically and histologically. Serum pepsinogen and plasma ghrelin levels were measured before and at 1, 12, 24, and 48 weeks after treatment. The study was approved by the Research Ethics Committee of the Keio University School of Medicine (no. 20140102; 8 July 2014). Results Eighteen patients completed the study protocol. Total and acyl plasma ghrelin levels demonstrated no significant change from before treatment to 48 weeks after eradication; however, there was a significant difference between open-type and closed-type atrophic gastritis. The PG I/II ratio increased significantly from 48 weeks after H. pylori eradication. The severity of the histological intestinal metaplasia scores correlated inversely with plasma total ghrelin levels from before to 48 weeks after H. pylori eradication. Conclusion Plasma levels of ghrelin correlate well with the level of gastric mucosal atrophy, even after H. pylori eradication.KEY MESSAGES Ghrelin plasma levels are associated with the progression of endoscopic atrophic gastritis, even at 48 weeks after H. pylori eradication. Ghrelin plasma levels are also associated with increased severity of histological intestinal metaplasia 48 weeks after H. pylori eradication. Pepsinogen I/II ratios increased immediately after H. pylori eradication and are inappropriate for assessing atrophic gastritis after H. pylori eradication.

We report the isolation of Helicobacter ailurogastricus, a Helicobacter species that infects cats and dogs, from a person with multiple refractory gastric ulcers. In addition to H. suis, which infects pigs, Helicobacter species that infect cats and dogs should be considered as potential gastric pathogens in humans.

Immunosenescence refers to the development of weakened and/or dysfunctional immune responses associated with aging. Several commensal bacteria can be pathogenic in immunosuppressed individuals. Although Klebsiella pneumoniae is a commensal bacterium that colonizes human mucosal surfaces, the gastrointestinal tract, and the oropharynx, it can cause serious infectious diseases, such as pneumonia, urinary tract infections, and liver abscesses, primarily in elderly patients. However, the reason why K. pneumoniae is a more prevalent cause of infection in the elderly population remains unclear. This study aimed to determine how the host's intestinal immune response to K. pneumoniae varies with age. To this end, the study analyzed an in vivo K. pneumoniae infection model using aged mice, as well as an in vitro K. pneumoniae infection model using a Transwell insert co-culture system comprising epithelial cells and macrophages. In this study, we demonstrate that growth arrest-specific 6 (Gas6), released by intestinal macrophages that recognize K. pneumoniae, inhibits bacterial translocation from the gastrointestinal tract by enhancing tight-junction barriers in the intestinal epithelium. However, in aging mice, Gas6 was hardly secreted under K. pneumoniae infection due to decreasing intestinal mucosal macrophages; therefore, K. pneumoniae can easily invade the intestinal epithelium and subsequently translocate to the liver. Moreover, the administration of Gas6 recombinant protein to elderly mice prevented the translocation of K. pneumoniae from the gastrointestinal tract and significantly prolonged their survival. From these findings, we conclude that the age-related decrease in Gas6 secretion in the intestinal mucosa is the reason why K. pneumoniae can be pathogenic in the elderly, thereby indicating that Gas6 could be effective in protecting the elderly against infectious diseases caused by gut pathogens.

The oil film thickness of the piston ring at the sliding surface affects oil consumption, friction loss and wear of the ring and liner in internal combustion engines. It is important to know the oil film thickness on the piston ring sliding surface in order to improve the engine efficiency. Accurate measurement of oil film thickness on the piston rings is difficult because the oil film thickness is extremely thin. A modified method is proposed for measuring thin oil film. The authors have measured the oil film thickness on the piston skirt and land to contribute. The optical measurement system and analytic method are improved. The presented method present the oil film thickness on the sliding surface of the top ring from the oil film visualization images. The verification of the measured oil film thickness carried out by comparing with the data obtained from the numerical calculation. For evaluating the effect of the oil characteristics, 0W-20 oil and #8 oil were tested with different engine speeds and different crank angle where different ring loads. It was confirmed that the top ring oil film thickness became thick due to the high engine speed. A large load on the top ring reduces the oil film thickness. The oil film became thick when the oil viscosity was high. The effect of oil viscosity on the oil film thickness of the top ring was clarified. The effect of the viscosity index improver was also discussed. It is shown from the experimental results that the present measurement system for the top ring oil film thickness has enough accuracy.

Abstract Circulating tumor DNA (ctDNA)-based next-generation sequencing (NGS) is a complementary and alternative test to tissue-based NGS. We performed NGS analysis of ctDNA samples collected from patients with EGFR-mutated non-small cell lung cancer (NSCLC) who received osimertinib; the samples were collected after second-line treatment, before osimertinib treatment, one week and one month after osimertinib treatment, and at the time of resistance formation. We examinedthe correlation with osimertinib efficacy. From January to December 2018, 34 patients with EGFR-mutated NSCLC harboring EGFR T790M mutations were enrolled, and a total of 132 peripheral blood samples were collected. The fragment sizes of EGFR-mutated ctDNAs were significantly shorter than that of their corresponding normal fragments. Osimertinib treatment of patients with shorter EGFR-mutated ctDNA fragments resulted in shorter progression-free survival (PFS). The disappearance time of EGFR-mutated fragment fractions and clonal evolution patterns (new driver mutation group, additional mutation group vs. attenuation group) were each associated with the PFS achieved with osimertinib treatment; however,multivariate analysis revealed that only shorter EGFR-mutated ctDNA fragments were associated with the PFS resulting from osimertinib treatment. EGFR-mutated ctDNA fragment size, time of disappearance of these fragments, and clonal evolution pattern were related to the effects of osimertinib. In particular, short EGFR-mutated ctDNA fragmentation may be closely related to osimertinib efficacy prediction.

Abstract Background Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders. Based on the various symptoms present in patients with functional dyspepsia postprandial distress syndrome (FD-PDS), routine agents such as acid suppressants, prokinetic drugs, and centrally acting drugs, offer limited treatment choices with potential side effects. As a preliminary clinical trial showed that the marketed product Zhizhu Kuanzhong Capsule (ZZKZ) can improve symptoms in FD-PDS patients, our study aims to provide further evidence on the clinical efficacy and safety of ZZKZ in the treatment of patients with FD-PDS. Methods In this multicenter, randomized, patient- and investigator-blinded, placebo-controlled, parallel-group clinical trial, we will recruit patients with FD-PDS from 18 hospitals in China and Australia. The trial will enroll patients with FD-PDS based on the Rome IV diagnostic criteria. A total of 480 eligible patients will be randomized 1:1 into either ZZKZ or placebo group with 8 weeks of treatment and 4 weeks of follow-up. The primary endpoint will be measured by a self-rated Visual Analogue Score (VAS) for the degree of discomfort with both symptoms of postprandial fullness and early satiation, recorded once a day and 7 days a week. The primary analysis will aim to compare the response rate for FD-PDS VAS score between the groups before and after 8 weeks of treatment with an alpha level of 0.05 (2-sided). Discussion This trial aims to strengthen the evidence for the efficacy and safety of ZZKZ, a marketed product, in treating FD-PDS. Compared to the previous clinical trial that targeted FD-PDS, this trial will have an 8-week double-blind treatment period to investigate the effect of long-term mediation through comparison with the placebo group. Trial registration ClinicalTrials.gov NCT03825692 . Registered on 28 January 2019

Abstract Breast cancer is one of the most common malignancies in women worldwide. Although most breast cancers are curable, in cases of metastasis, many are often found in the lungs, bones, liver, and central nervous system; however, metastasis to the gastrointestinal tract is rare. Invasive lobular carcinoma, which represents only 5%–10% of breast cancers, has a higher risk of metastasis to the gastrointestinal tract than invasive ductal carcinoma. Here, we report a rare case of gastrointestinal metastasis of invasive lobular carcinoma that spread extensively to the colonic mucosa. Given the improved survival rates of breast cancer patients with current treatments, many rarer metastatic diseases, including gastrointestinal metastases, are likely to be increased in the future.

Summary: Helicobacter suis, hosted by hogs, is the most prevalent gastric non-Helicobacter pylori Helicobacter species found in humans. Recent studies have suggested that H. suis infection has caused many cases of gastric disease, but the transmission route from hogs remains unclear. Diagnostic methods based on H. suis urease activity often yield negative results, and there is no reliable method for diagnosing H. suis infection in clinical practice without gastric biopsy specimens. This study presents the world’s first use of whole-bacterial cell ELISA to simultaneously assess H. suis and H. pylori infections. The ELISAs showed high accuracy, with an area under the ROC curve of 0.96, 100% sensitivity, 92.6% specificity, 76.9% positive predictive value, and 100% negative predictive value for the H. suis test, and an area under the ROC curve of 0.92, 88.2% sensitivity, 87.5% specificity, 65.2% positive predictive value, and 96.6% negative predictive value for the H. pylori test.

A 19-year-old man visited our hospital because of diarrhea and blood and liver dysfunction. Magnetic and endoscopic retrograde cholangiography revealed diffuse narrowing of the common biliary tract and intrahepatic biliary tract. A biopsy specimen from the narrowed area of the common biliary tract revealed IgG4-related sclerosing cholangitis (IgG4-SC). Colonoscopy showed multiple aphthoid colitis. He was treated with corticosteroids, and the levels of hepatobiliary enzymes, IgG, and IgG4 gradually decreased. This is an extremely rare case of colitis in which the patient had a phenotype of sclerosing cholangitis similar to IgG4-SC, which was finally diagnosed as primary sclerosing cholangitis.

Abstract Background Malignant ascites often causes discomfort in advanced cancer patients. Paracentesis is the most common treatment modality, but it requires frequently repeated treatment. Cell-free and concentrated ascites reinfusion therapy (CART) may prolong the paracentesis interval, but controlled trials are lacking. We assessed the feasibility of a randomized controlled trial of CART vs. paracentesis alone for patients with refractory malignant ascites. Methods This study was an open-label, fast-track, randomized controlled, feasibility trial. Patients admitted to four designated cancer hospitals who received no further anticancer treatments were eligible. Patients were randomly assigned 1:1 to a CART arm or control (simple paracentesis) arm. The feasibility endpoint was the percentage of patients who completed the study intervention. Secondary endpoints included paracentesis-free survival, patient’s request on the questionnaire for paracentesis (PRO-paracentesis)-free survival (the period until the patients first reported that they would want paracentesis if indicated), and adverse events. Results We screened 953 patients for eligibility. Of 61 patients with refractory malignant ascites, 21 patients were determined as eligible. Finally, 20 patients consented and were allocated; 18 patients (90%, 95% CI: 68.3–98.8) completed the study intervention. All patients had an ECOG performance status of 3 or 4. The median drained ascites volume was 3,200 mL in the CART arm and 2,500 mL in the control arm. In the CART arm, the median reinfused albumin volume was 12.6 g. Median paracentesis-free survivals were 5 days (95% CI: 2–6) in the CART arm, and 6 days (3–9) in the control arm. Median PRO-paracentesis-free survivals were 4 days (2–5) and 5 days (1–9), respectively. A total of 73% of patients received paracentesis within 2 days from their first request for the next paracentesis. One patient in the CART arm developed Grade 1 fever. Conclusions A fast-track randomized controlled trial of CART for patients with malignant ascites is feasible. The efficacy and safety of CART should be assessed in future trials. PRO-paracentesis-free survival may be a complementary outcome measure with paracentesis-free survival in future trials. Trial registration Registered at University Hospital Medical Information Network Clinical Trial Registry as UMIN000031029 . Registered on 28/01/2018.

Background and aimAdherent-invasive E. coli (AIEC) has been identified as a pathobiont associated with Crohn’s disease (CD), that prefers to grow in inflammatory conditions. Although the colonization by AIEC is implicated in the progression of the disease and exacerbates inflammation in murine colitis models, the recognition and response of host immunity to AIEC remains elusive.MethodsAntibiotic treated female C57BL/6 mice were inoculated by commensal E. coli and LF82 AIEC strains. Luminal-IgA fractions were prepared from feces and their binding to AIEC and other strains was assessed to confirm specificity. IgA binding to isogenic mutant strains was performed to identify the functional molecules that are recognized by AIEC specific IgA. The effect of IgA on epithelial invasion of LF82 strain was confirmed using in vitro invasion assay and in vivo colonization of the colonic epithelium.ResultsPersistent colonization by AIEC LF82 induced secretion of luminal IgA, while commensal E. coli strain did not. Induced anti-LF82 IgA showed specific binding to other AIEC strains but not to the commensal, non-AIEC E. coli strains. Induced IgA showed decreased binding to LF82 strains with mutated adhesin and outer membrane proteins which are involved in AIEC – epithelial cell interaction. Consistently, LF82-specific IgA limited the adhesion and invasion of LF82 in cultured epithelial cells, which seems to be required for the elimination in the colonic epithelium in mice.ConclusionThese results demonstrate that host immunity selectively recognizes pathobiont E. coli, such as AIEC, and develop specific IgA. The induced IgA specific to pathobiont E. coli, in turn, contributes to preventing the pathobionts from accessing the epithelium.

Background/Aims The recovery room used after endoscopy has limited capacity, and an efficient flow of the endoscopy unit is desired. We investigated the duration of hospital stay after endoscopy and the risk factors for prolonged hospital stay among outpatients. Methods We retrospectively studied consecutive patients who underwent esophagogastroduodenoscopy or colonoscopy at the Toyoshima Endoscopy Clinic. We collected data on age, sex, body weight, midazolam and pethidine dosage, respiratory depression during endoscopy, and duration of hospital stay after endoscopy (scope out to check out). Risk factors for prolonged hospital stay (>100 minutes) were identified using multiple logistic regression analysis. Results We enrolled 3,898 patients, including 3,517 (90.2%) patients tested under sedation and 381 (9.8%) patients tested without sedation. Overall, 442 (11.3%) patients had prolonged stay (>100 min). The mean time difference between sedation group and non-sedation group was 44.2 minutes for esophagogastroduodenoscopy and 39.1 minutes for colonoscopy. Age (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.014−1.036), female sex (OR, 1.657; 95% CI, 1.220−2.249), and midazolam dose (OR, 1.019; 95% CI, 1.013−1.026) were independently associated with prolonged hospital stay after esophagogastroduodenoscopy, with similar results for colonoscopy. Conclusions Old age, female sex, and midazolam dose were independent risk factors for prolonged hospital stay after endoscopy.

Purpose: We aimed to investigate the effects of different multi-leaf collimator (MLC) speed constraints in volumetric modulated radiotherapy (VMAT) on the robustness of treatment plans for central lung cancer patients. Method and Materials: Twenty patients with central lung tumor who underwent stereotactic body radiotherapy (SBRT) with the VMAT technique at our hospital were included in this retrospective study. The reference plans were created with 3 different MLC speed constraints (Plan A: 0.1 cm/deg., Plan B: 0.3 cm/deg., and Plan C: 0.5 cm/deg.) with a 50-Gy/8Fr, planning target volume (PTV) D 95% prescription. In each of these plans, setup errors from 1 to 5 mm were intentionally added in the direction of the central organ at 1-mm intervals (300 plans [20 cases × 3 MLC speeds × 5 error plans] were created in total). Each plan was then calculated by the same beam conditions as each reference plan. The actual average MLC speed and dose difference between the reference plan and the error-added plan were then calculated and compared among the 3 MLC speeds. Results: In the reference plans, the actual average MLC speeds were 0.25 ± 0.04, 0.34 ± 0.07, and 0.39 ± 0.12 cm/deg. for Plan A, Plan B, and Plan C, respectively ( P

We investigated the effect of increased pH induced by acid suppressants on the viability of non–Helicobacter pylori helicobacters (NHPHs) within parietal cell intracellular canaliculi and fundic glandular lumina by immunohistochemistry, electron microscopy, quantitative PCR, urea breath tests, and using a bilayer culture system. Three months before the experiment, mice were infected with the NHPH H. suis and then treated with famotidine (2 mg/kg body weight [BW], once daily), lansoprazole (30 mg/kg BW, once daily), or vonoprazan (20 mg/kg BW, once daily) for 3 days. Immunohistochemical studies using the TUNEL method, quantitative PCR analysis, and urea breath tests were performed. PCR analysis showed a decrease in the NHPH quantity after vonoprazan treatment. Urea breath tests revealed a significant decrease in the NHPH urease activity after vonoprazan, lansoprazole, and famotidine treatments for 3 days; however, 4 days after the treatment, urease activity reversed to the pretreatment level for each treatment group. Electron microscopy revealed an increase in the damaged NHPH after vonoprazan treatment. The TUNEL method revealed apoptotic NHPH within parietal cells after vonoprazan treatment. The bilayer culture results demonstrated that NHPH moved more quickly at a pH of 4.0 than at a pH of 3.0, 5.0, and 6.5, and electron microscopy revealed a change from the spiral form to the coccoid form under near-neutral pH conditions. We thus proposed that acid suppressants, especially vonoprazan, induce NHPH damage by altering pH.

Abstract Background While double primary cancers are common in breast cancer patients, co-existence of primary gastric cancer and gastric metastases of breast cancer is exceedingly rare. Case presentation A 51-year-old woman receiving chemotherapy for breast cancer presented with melena and presyncope. A circumferential thickening of the pylorus and small submucosal tumor-like lesions in the gastric fundus and corpus were confirmed on endoscopy. Immunohistochemistry of biopsies revealed that the former was composed of poorly differentiated gastric cancer cells, while the latter were breast cancer metastases. Distal gastrectomy was performed. Pathological evaluation of the resected specimen revealed gastric adenocarcinoma in the pyloric lesion and breast countless cancer metastases throughout the remainder of the stomach, with positive margins. One lymph node had evidence of both stomach cancer and breast cancer metastases, forming a collision tumor. Despite a successful surgery, the patient died 6 months later due to progression of breast cancer. Conclusion We report a case of synchronous primary gastric adenocarcinoma and gastric metastases of breast cancer. Inter-disciplinary collaboration is crucial in determining the optimal treatment in double cancers.

Abstract The most frequent mechanism of resistance after 1st/2nd-generation (G) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is secondary point mutation Thr790Met (T790M) in EGFR. Afatinib followed by osimertinib (Afa group) may provide better outcomes for T790M-positive non-small cell lung cancer (NSCLC) than 1st-G EGFR-TKI followed by osimertinib (1st-G group). We studied 111 consecutive NSCLC patients with T790M mutation treated with osimertinib after progression following 1st/2nd-G EGFR-TKI between March 28, 2016 and March 31, 2018. We analyzed the ratio of T790M to EGFR-activating mutation (T790M ratio) in post EGFR-TKI resistance re-biopsy tissue using droplet digital polymerase chain reaction. And investigated whether afatinib purified the T790M mutation more than 1st-G EGFR-TKI. Among 60 patients with preserved re-biopsy tissue, we analyzed 38 having adequate DNA content. The response rate in Afa group was 81.8% (n = 11) and 1st-G group was 85.2% (n = 27). The mean T790M ratio in total population was 0.3643. The ratio in those with response to osimertinib was significantly higher than in the non-responders (0.395, 0.202; p = 0.0231) and was similar in Afa and 1st-G group (0.371, 0.362; p = 0.9693). T790M ratio significantly correlated with osimertinib response and was similar between the 1st/2nd-G EGFR-TKIs in 1st/2nd-G EGFR-TKI-refractory tumors.

Abstract Background Despite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to ICI therapy are scarce. Therefore, we first investigated the characteristics associated with shorter durable responses of ICI treatment and revealed the clinical patterns of AR and prognosis of the patients involved. Methods We conducted a retrospective multi-center cohort study that included NSCLC patients with PD-L1 tumor proportion scores of ≥50% who received first-line pembrolizumab and showed response to the therapy. Among patients showing response, progression-free survival (PFS) was investigated based on different clinically relevant factors. AR was defined as disease progression after partial or complete response based on Response Evaluation Criteria in Solid Tumors. Among patients with AR, patterns of AR and post-progression survival (PPS) were investigated. Oligoprogression was defined as disease progression in up to 5 individual progressive lesions. Results Among 174 patients who received first-line pembrolizumab, 88 showed response and were included in the study. Among these patients, 46 (52%) developed AR. Patients with old age, poor performance status (PS), at least 3 metastatic organs, or bone metastasis showed significantly shorter PFS. Among 46 patients with AR, 32 (70%) developed AR as oligoprogression and showed significantly longer PPS than those with non-oligoprogressive AR. Conclusions Patients with old age, poor PS, at least 3 metastatic organs, or bone metastasis showed shorter durable responses to pembrolizumab monotherapy. Oligoprogressive AR was relatively common and associated with better prognosis. Further research is required to develop optimal approaches for the treatment of these patients.

Gastric cancer remains one of the most common causes of cancer-related death worldwide, although the incidence is declining gradually. The primary risk factor for gastric cancer is Helicobacter pylori infection. The Kyoto global consensus report recommends eradication of H. pylori in all infected patients. However, because it is difficult to stratify the risk of carcinogenesis among patients with a history of H. pylori infection, annual endoscopic surveillance is performed for everyone after eradication. This review summarizes the current approaches used to screen for novel molecules that could assist in the diagnosis of gastric cancer and reduce mortality. Most well-studied molecules are tissue protein biomarkers expressed by the gastric epithelium and associated with metaplasia-dysplasia-carcinoma sequences. Other strategies focus on the origin of cancer stem cell-related markers, such as CD44, and immune reaction-related markers, such as matrix metallopeptidases. Noninvasive methods such as blood-based approaches are more attractive. Serum pepsinogen levels predict the severity of gastric mucosal atrophy before H. pylori eradication, whereas plasma ghrelin levels are associated with atrophy even after eradication. Cell-free DNAs and RNAs are attractive tools for the early detection of cancer. These ideas could lead to the development of more personalized strategies for cancer prevention based on cutting-edge technologies.

Bronchoalveolar lavage is commonly performed to assess inflammation and identify responsible pathogens in lung diseases. Findings from bronchoalveolar lavage might be used to evaluate the immune profile of the lung tumor microenvironment (TME). To investigate whether bronchoalveolar lavage fluid (BALF) analysis can help identify patients with non–small cell lung cancer (NSCLC) who respond to immune checkpoint inhibitors (ICIs), BALF and blood were prospectively collected before initiating nivolumab. The secreted molecules, microbiome, and cellular profiles based on BALF and blood analysis of 12 patients were compared with regard to therapeutic effect. Compared with ICI nonresponders, responders showed significantly higher CXCL9 levels and a greater diversity of the lung microbiome profile in BALF, along with a greater frequency of the CD56+ subset in blood T cells, whereas no significant difference in PD-L1 expression was found in tumor cells. Antibiotic treatment in a preclinical lung cancer model significantly decreased CXCL9 in the lung TME, resulting in reduced sensitivity to anti–PD-1 antibody, which was reversed by CXCL9 induction in tumor cells. Thus, CXCL9 might be associated with the lung TME microbiome, and the balance of CXCL9 and lung TME microbiome could contribute to nivolumab sensitivity in patients with NSCLC. BALF analysis can help predict the efficacy of ICIs when performed along with currently approved examinations.

Abstract Background and Aim Endoscopy‐based Kyoto classification predicts the risk of Helicobacter pylori infection and gastric cancer; however, the change in score following H. pylori eradication remains unknown. We retrospectively compared the Kyoto score before and after H. pylori eradication. Methods H. pylori‐positive patients who underwent baseline esophagogastroduodenoscopy (EGD), successful H. pylori eradication, and surveillance EGD were enrolled. The Kyoto score is a sum of scores for atrophy (Kimura‐Takemoto atrophic‐border classification none or C1: 0, C‐II or C‐III: 1, O‐I to O‐III: 2), intestinal metaplasia (none: 0, antrum: 1, corpus and antrum: 2), enlarged folds (absence: 0, presence: 1), nodularity (absence: 0, presence: 1), and diffuse redness (none: 0, mild: 1, severe: 2) and ranges from 0 to 8. Results Eighty‐three patients (mean age: 54.9 years; 65.1% women) were enrolled. The mean duration from successful eradication to surveillance EGD was 256 days. The Kyoto score significantly decreased from 3.90 to 2.78 following H. pylori eradication (P

Abstract Background Vertebroplasty with posterior spinal fusion (VP + PSF) is one of the most widely accepted surgical techniques for treating osteoporotic vertebral collapse (OVC). Nevertheless, the effect of the extent of fusion on surgical outcomes remains to be established. This study aimed to evaluate the surgical outcomes of short- versus long-segment VP + PSF for OVC with neurological impairment in thoracolumbar spine. Methods We retrospectively collected data from 133 patients (median age, 77 years; 42 men and 91 women) from 27 university hospitals and their affiliated hospitals. We divided patients into two groups: a short-segment fusion group (S group) with 2- or 3-segment fusion (87 patients) and a long-segment fusion group (L group) with 4- through 6-segment fusion (46 patients). Surgical invasion, clinical outcomes, local kyphosis angle (LKA), and complications were evaluated. Results No significant differences between the two groups were observed in terms of neurological recovery, pain scale scores, and complications. Surgical time was shorter and blood loss was less in the S group, whereas LKA at the final follow-up and correction loss were superior in the L group. Conclusion Although less invasiveness and validity of pain and neurological relief are secured by short-segment VP + PSF, surgeons should be cautious regarding correction loss.

Introduction: Osteoporotic vertebral fracture (OVF) is the most common osteoporotic fracture, and some patients require surgical intervention to improve their impaired activities of daily living with neurological deficits. However, many previous reports have focused on OVF around the thoracolumbar junction, and the surgical outcomes of lumbar OVF have not been thoroughly discussed. We aimed to investigate the surgical outcomes for lumbar OVF with a neurological deficit. Methods: Patients who underwent fusion surgery for thoracolumbar OVF with a neurological deficit were enrolled at 28 institutions. Clinical information, comorbidities, perioperative complications, Japanese Orthopaedic Association scores, visual analog scale scores, and radiographic parameters were compared between patients with lower lumbar fracture (L3-5) and those with thoracolumbar junction fracture (T10-L2). Each patient with lower lumbar fracture (L group) was matched with to patients with thoracolumbar junction fracture (T group). Results: A total 403 patients (89 males and 314 females, mean age: 73.8 ± 7.8 years, mean follow-up: 3.9 ± 1.7 years) were included in this study. Lower lumbar OVF was frequently found in patients with lower bone mineral density. After matching, mechanical failure was more frequent in the L group (L group: 64%, T group: 39%; p < 0.001). There was no difference between groups in the clinical and radiographical outcomes, although the rates of complication and revision surgery were still high in both groups. Conclusions: The surgical intervention for OVF is effective in patients with myelopathy or radiculopathy regardless of the surgical level, although further study is required to improve clinical and radiographical outcomes. Level of evidence: Level III

Abstract Background The optimal treatment of osteoporosis after reconstruction surgery for osteoporotic vertebral fractures (OVF) remains unclear. In this multicentre retrospective study, we investigated the effects of typically used agents for osteoporosis, namely, bisphosphonates (BP) and teriparatide (TP), on surgical results in patients with osteoporotic vertebral fractures. Methods Retrospectively registered data were collected from 27 universities and affiliated hospitals in Japan. We compared the effects of BP vs TP on postoperative mechanical complication rates, implant-related reoperation rates, and clinical outcomes in patients who underwent posterior instrumented fusion for OVF. Data were analysed according to whether the osteoporosis was primary or glucocorticoid-induced. Results A total of 159 patients who underwent posterior instrumented fusion for OVF were included. The overall mechanical complication rate was significantly lower in the TP group than in the BP group (BP vs TP: 73.1% vs 58.2%, p = 0.045). The screw backout rate was significantly lower and the rates of new vertebral fractures and pseudoarthrosis tended to be lower in the TP group than in the BP group. However, there were no significant differences in lumbar functional scores and visual analogue scale pain scores or in implant-related reoperation rates between the two groups. The incidence of pseudoarthrosis was significantly higher in patients with glucocorticoid-induced osteoporosis (GIOP) than in those with primary osteoporosis; however, the pseudoarthrosis rate was reduced by using TP. The use of TP also tended to reduce the overall mechanical complication rate in both primary osteoporosis and GIOP. Conclusions The overall mechanical complication rate was lower in patients who received TP than in those who received a BP postoperatively, regardless of type of osteoporosis. The incidence of pseudoarthrosis was significantly higher in patients with GIOP, but the use of TP reduced the rate of pseudoarthrosis in GIOP patients. The use of TP was effective to reduce postoperative complications for OVF patients treated with posterior fusion.

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).

Abstract Background Most of the previous studies about the surgical treatment of dropped head syndrome (DHS) are small case series, and their primary outcome measures were cervical alignment parameters. Therefore, little is known about the associations between pre- and postoperative global sagittal alignment in the whole spine and the clinical outcomes of the surgical treatment of DHS. In this study, we investigated the surgical outcomes of DHS, including correction of cervical and global spinal sagittal alignment. Methods This study was a retrospective observational study. Fifteen patients with DHS who had undergone correction surgery were enrolled. Surgical outcomes, including complications and implant failures, were investigated. We assessed cervical alignment parameters as well as spinopelvic global alignment parameters, including pelvic incidence (PI), lumbar lordosis (LL), and C7-sacral sagittal vertical axis (SVA). We examined the changes in these parameters using pre- and posoperative whole spine lateral radiographs. The parameters were compared between the failure and nonfailure groups. Results Recurrence of sagittal imbalance and horizontal gaze difficulty was observed in 6 cases (40%). In all, 3 cases (20%) exhibited a distal junctional failure and required multiple surgeries with extension of fusion. Of all the radiographic parameters compared between the failure and nonfailure groups, significant differences were only observed in pre and postoperative SVA and PI-LL. Conclusions Our results suggest that the global sagittal alignment parameters, including PI-LL and SVA, were different between the patients with failure and non failure, and these parameters might have notable impacts on surgical outcomes. Surgeons should consider PI-LL and SVA while determining the surgical course for patients with DHS.

Abstract Background Pembrolizumab is effective as first-line therapy against advanced non-small cell lung cancer (NSCLC) in patients with programmed death ligand-1 (PD-L1) expression levels ≥50% [1]. However, it is not effective in all patients, and the factors predicting responses among this population remain unknown. Methods We retrospectively analyzed patients with NSCLC and a PD-L1 tumor proportion score (TPS) > 50%, who received first-line monotherapy with pembrolizumab from February 1, 2017 to April 30, 2018. The study included 11 hospitals, which participated in the Hanshin Oncology clinical Problem Evaluation group (HOPE). We analyzed the differences between responders and non-responders in terms of age, sex, performance status score, degree of progression, histological type, smoking history, expression of PD-L1, use of steroids prior to treatment, metastasis site, and laboratory data. Results A total of 205 patients were included in this study. Of those, 108 patients exhibiting complete or partial response were defined as responders. Those exhibiting progressive disease (N = 52) were defined as non-responders. In the univariate analysis, Eastern Cooperative Oncology Group performance status score ≥ 2 (p = 0.0832), stage IV disease or recurrence (p = 0.0487), PD-L1 TPS 50–89% (p = 0.0657), use of steroids prior to the administration of pembrolizumab (p = 0.0243), malignant pleural effusion (p = 0.0032), and baseline C-reactive protein (CRP) levels > 1.0 mg/dL (p = 0.0390) were significantly associated with non-response to treatment. In the multivariate analysis, use of steroids prior to the administration of pembrolizumab (odds ratio [OR]: 5.86; 95% confidence interval [CI]: 1.32–31.8; p = 0.0200), malignant pleural effusion (OR: 2.68; 95% CI: 1.15–6.35; p = 0.0228), and baseline CRP > 1.0 mg/dL (OR: 2.17; 95% CI: 1.03–4.68; p = 0.0402) were significantly associated with non-response to treatment. Conclusion In real-world patients with NSCLC and a PD-L1 TPS ≥50%, use of steroids prior to treatment, malignant pleural effusion, and baseline CRP levels > 1.0 mg/dL reduced the response of first-line monotherapy with pembrolizumab.

Oral conditions are relatively common in patients with inflammatory bowel disease (IBD). However, the contribution of oral maladies to gut inflammation remains unexplored. Here, we investigated the effect of periodontitis on disease phenotypes of patients with IBD. In all, 60 patients with IBD (42 with ulcerative colitis [UC] and 18 with Crohn’s disease [CD]) and 45 healthy controls (HCs) without IBD were recruited for this clinical investigation. The effects of incipient periodontitis on the oral and gut microbiome as well as IBD characteristics were examined. In addition, patients were prospectively monitored for up to 12 months after enrollment. We found that, in both patients with UC and those with CD, the gut microbiome was significantly more similar to the oral microbiome than in HCs, suggesting that ectopic gut colonization by oral bacteria is increased in patients with IBD. Incipient periodontitis did not further enhance gut colonization by oral bacteria. The presence of incipient periodontitis did not significantly affect the clinical outcomes of patients with UC and CD. However, the short CD activity index increased in patients with CD with incipient periodontitis but declined or was unchanged during the study period in patients without periodontitis. Thus, early periodontitis may associate with worse clinically symptoms in some patients with CD.

Introduction: The prevalence of patients with osteoporosis continues to increase in aging societies, including Japan. The first choice for managing osteoporotic vertebral compression fracture (OVF) is conservative treatment. Failure in conservative treatment for OVF may lead to non-union or vertebral collapse, resulting in neurological deficit and subsequently requiring surgical intervention. This multicenter nationwide study in Japan was conducted to comprehensively understand the outcomes of surgical treatments for OVF non-union. Methods: This multicenter, retrospective study included 403 patients (89 males, 314 females, mean age 73.8 ± 7.8 years, mean follow-up 3.9 ± 1.7 years) with neurological deficit due to vertebral collapse or non-union after OVF at T10-L5 who underwent fusion surgery with a minimum 1-year follow-up. Radiological and clinical outcomes at baseline and at the final follow-up (FU) were evaluated. Results: OVF was present at a thoracolumbar junction such as T12 (124 patients) and L1 (117 patients). A majority of OVF occurred after a minor trauma, such as falling down (55.3%) or lifting objects (8.4%). Short segment fusion, including affected vertebra, was conducted (mean 4.0 ± 2.0 vertebrae) with 256.8 minutes of surgery and 676.1 g of blood loss. A posterior approach was employed in 86.6% of the patients, followed by a combined anterior and posterior (8.7%), and an anterior (4.7%) approach. Perioperative complications and implant failures were observed in 18.1% and 41.2%, respectively. VAS scores of low back pain (74.7 to 30.8 mm) and leg pain (56.8 to 20.7 mm) improved significantly at FU. Preoperatively, 52.6% of the patients were unable to walk and the rate of non-ambulatory patients decreased to 7.5% at FU. Conclusions: This study demonstrated that substantial improvement in activity of daily living (ADL) was achieved by fusion surgery. Although there was a considerable rate of complications, fusion surgery is beneficial for elderly OVF patients with non-union.

Introduction: Approximately 3% of osteoporotic vertebral fractures develop osteoporotic vertebral collapse (OVC) with neurological deficits, and such patients are recommended to be treated surgically. However, a proximal junctional fracture (PJFr) following surgery for OVC can be a serious concern. Therefore, the aim of this study is to identify the incidence and risk factors of PJFr following fusion surgery for OVC. Methods: This study retrospectively analyzed registry data collected from facilities belonging to the Japan Association of Spine Surgeons with Ambition (JASA) in 2016. We retrospectively analyzed 403 patients who suffered neurological deficits due to OVC below T10 and underwent corrective surgery; only those followed up for 2 years were included. Potential risk factors related to the PJFr and their cut-off values were calculated using multivariate logistic regression analysis and receiver operating characteristic (ROC) analysis. Results: Sixty-three patients (15.6%) suffered PJFr during the follow-up (mean 45.7 months). In multivariate analysis, the grade of osteoporosis (grade 2, 3: adjusted odds ratio (aOR) 2.92; p=0.001) and lower instrumented vertebra (LIV) level (sacrum: aOR 6.75; p=0.003) were independent factors. ROC analysis demonstrated that lumbar bone mineral density (BMD) was a predictive factor (area under curve: 0.72, p=0.035) with optimal cut-off value of 0.61 g/cm2 (sensitivity, 76.5%; specificity, 58.3%), but that of the hip was not (p=0.228). Conclusions: PJFr was found in 16% cases within 4 years after surgery; independent risk factors were severe osteoporosis and extended fusion to the sacrum. The lumbar BMD with cut-off value 0.61 g/cm2 may potentially predict PJFr. Our findings can help surgeons select perioperative adjuvant therapy, as well as a surgical strategy to prevent PJFr following surgery.

Spastic paraplegia 30 is a recently established autosomal recessive disease characterized by a complex form of spastic paraplegia associated with neuropathy. Homozygous mutations of KIF1A reportedly lead to hereditary spastic paraplegia or hereditary sensory and autonomic neuropathy type 2 (HSAN2), whereas heterozygous mutations can cause nonsyndromic and syndromic intellectual disability (MRD9). Here we report the case of a 37-year-old female who presented with gait disturbance complicated with moyamoya disease. Results: The patient exhibited hypotonia during infancy, after which intellectual disability, epileptic fits, spastic paraplegia, and cerebellar atrophy occurred. Genetic analysis revealed a novel de novo mutation (c.254C > A, p.A85D) in the motor domain of KIF1A. Keywords: KIF1A, Spastic paraplegia 30: SPG30, Moyamoya disease, Gene, HSAN2, Mental retardation, Autosomal dominant 9, MRD9

Abstract Background To date, there have been little published data on surgical outcomes for patients with PD with thoracolumbar OVF. We conducted a retrospective multicenter study of registry data to investigate the outcomes of fusion surgery for patients with Parkinson’s disease (PD) with osteoporotic vertebral fracture (OVF) in the thoracolumbar junction. Methods Retrospectively registered data were collected from 27 universities and their affiliated hospitals in Japan. In total, 26 patients with PD (mean age, 76 years; 3 men and 23 women) with thoracolumbar OVF who underwent spinal fusion with a minimum of 2 years of follow-up were included (PD group). Surgical invasion, perioperative complications, radiographic sagittal alignment, mechanical failure (MF) related to instrumentation, and clinical outcomes were evaluated. A control group of 296 non-PD patients (non-PD group) matched for age, sex, distribution of surgical procedures, number of fused segments, and follow-up period were used for comparison. Results The PD group showed higher rates of perioperative complications (p

Background & Aims: CD44 variant 9 (CD44v9)-positive cancer stem-like cells strongly contribute to the development and recurrence of gastric cancer. However, the origin of CD44v9-positive cells is uncertain. Methods: CD44v9, β-catenin, and epithelial splicing regulatory protein 1 signals were assessed by real-time reverse-transcription polymerase chain reaction, immunoblot analysis, or immunofluorescence microscopy. Capping actin protein of muscle Z-line α subunit 1 (CAPZA1) expression was assessed by immunoblot analysis or immunohistochemical analysis of Mongolian gerbils' gastric mucosa or human biopsy specimens. Levels of oxidative stress were assessed by measuring malondialdehyde and protein carbonylation. Histone H3 acetylation levels in the CAPZA1 proximal promoter region were measured by using chromatin immunoprecipitation analysis with an antibody against the acetylated histone H3 in human gastric carcinoma cell line (AGS) cells. Results: CD44v9 is expressed in CAPZA1-overexpressing cells in human gastric cancer tissues. CAPZA1 overexpression enhanced expression of β-catenin, which is a transcription factor for CD44, and epithelial splicing regulatory protein 1, which increases alternative splicing of CD44 to generate CD44v9. CAPZA1-overexpressing cells after cytotoxin-associated gene A accumulation showed CD44v9 expression by inducing nuclear accumulation of β-catenin, concomitant with the enhancement of expression of Sal-like protein 4 and Krüppel-like factor 5, which encode reprogramming factors. Oxidative stress increased the CAPZA1 expression in AGS cells through the enhancement of histone H3 acetylation of CAPZA1 promoter. CAPZA1 expression was increased depending on oxidative stress in H pylori–infected gastric mucosa. Conclusions: CD44v9 expression is evoked from CAPZA1-overexpressing cells after accumulation of cytotoxin-associated gene A. Our findings provide important insights into the mechanisms underlying the development of CD44v9-positive cells. Keywords: Autophagy, CagA, Cancer Stem Cells, CD44v9, Eradication Therapy

This was a study of the case of a 60-year-old woman who presented with a six-month history of headache and numbness radiating to the right arm. MRI revealed a fusiform intramedullary spinal tumor spanning C2 to C5 at the hospital where she first presented. As her right upper limb weakness had presented gradually, she visited our hospital after one and a half years. Neurological examination revealed muscle weakness in the right deltoid, but no sensory disturbance. The patient underwent a C2-C6 total laminectomy and posterior midline myelotomy from the posterior median fissure of the spinal cord. The intraoperative histological diagnosis was glioma. Pathological findings in low magnification demonstrated clusters of small uniform nuclei embedded in a dense and fibrillary matrix in hematoxylin-eosin staining (H.E.). On immunohistochemical staining, the tumor cells were weakly positive for glial fibrillary acidic protein (GFAP), but negative for the epithelial membrane antigen (EMA). The histopathological findings were consistent with the diagnosis of a subependymoma. However, the MIB-1 labeling index was of moderately high level up to approximately 8%. In this case, we performed total resection because the tumor had rapidly increased in size and was of atypical form in histological findings. It should be minded that some of subependymomas have a possibility of rapidly increasing in size with progressing neurological deficits.

Purpose: Gait and posture disorder severely impedes the quality of life of affected patients with lumbar spinal canal stenosis (LSCS). Despite the major health concern, there is a paucity of literature about the relationships among spatiotemporal gait parameters and spinal sagittal parameters. This is a cross sectional study performed in a single tertiary referral center to determine the relationships among spatiotemporal gait parameters and spinal sagittal parameters in patients with LSCS. Methods: A total of 164 consecutive patients with LSCS, 87 men and 77 women with mean age of 70.7 years, were enrolled. Spatiotemporal gait parameters were studied using a gait analysis system. Spinal sagittal parameters were studied including sagittal vertical axis (SVA), thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic inclination (PI), and pelvic tilt (PT) both in the neutral and stepped positions. Results: SVA was significantly larger in the stepped position than in the neutral position (neutral position, 72.5 mm; stepped position, 96.8 mm; p = 0.003). Parameters regarding the pelvis exhibited significant differences, which could represent pelvic anteversion in the stepped position. By stepwise multiple regression analysis, the prediction models, containing SVA (neutral) and PT (stepped) for double supporting phase, exhibited statistical significance, and accounted for approximately 50% of the variance. Conclusions: The present study provides statistically established evidence of correlation among spatiotemporal gait parameters and spinal sagittal parameters. Differences between sagittal parameters in neutral and stepped position may stand for the postural control during gait cycle, and increased SVA in neutral position and increased PT in stepped position may correlate with prolonged double supporting phase.

Background: Dropped head syndrome (DHS) can be divided into two types, the positive sagittal vertical axis (SVA) type and the negative SVA type. However, the cervical sagittal alignment of DHS including global sagittal spinal alignment and the typical cervical alignment of the types of DHS is still unclear. The purpose of this study was to clarify the character of cervical sagittal alignment of DHS and analyze the relationship between cervical sagittal alignment and global sagittal spinal alignment. Methods: The subjects were 35 DHS patients (10 men, 25 women, mean 71.1 years old). They were divided into two groups: negative DHS (N-DHS group, SVA < 0 mm) and positive DHS group (P-DHS group, SVA ≥ 0 mm). As control, 28 age-matched cervical spondylosis patients (CS, 21 men, 7 women, mean 67.4 years old) were analyzed. The following parameters were measured on lateral global-spine standing radiographs: cervical SVA (C2-C7SVA), O-C2A (O-C2 angle), C2 slope (C2S), C2-7A (C2-7 angle), T1 slope (T1S) and C7SVA. Results: The results of measurements of each of the averaged sagittal alignment parameters were (CS, P-DHS, N-DHS): C2-7SVA(26.2 mm, 47.3 mm, 44.5 mm), O-C2 angle (35.0°, 37.1°, 39.3°), C2S (16.5°, 31.4°, 33.8°), C2-7A (9.3°, 9.9°, −16.6°), T1S (22.9°, 39.7°, 25.7°), C7SVA (35.3 mm, 51.0 mm, −43.1 mm). C2-C7SVA and C2S were significantly larger in both types of DHS compared to CS. Comparing P-DHS with N-DHS, C2-C7A and T1S were significantly smaller in N-DHS. Conclusions: O-C2A did not differ significantly among CS, P-DHS and N-DHS. In DHS patients, C2-7SVA and C2S were significantly larger than those of CS regardless of the type of DHS. The typical cervical sagittal alignment of DHS was different between P-DHS and N-DHS. In P-DHS, C2-7A and T1S were larger than those in N-DHS and the imbalance of thoraco-lumbar alignment should be noted.

Despite improvements in imaging modalities, causative lead points in adult intussusception may be difficult to diagnose. Such lead points can be malignant, causing recurrence or metastases if left unresected. We describe a case of transient adult jejunojejunal intussusception, in which intraoperative endoscopy was used to confirm the absence of a lead point. A 39-year-old woman with a history of laparoscopic oophorectomy presented with epigastric pain, nausea, and vomiting. Contrast computed tomography revealed jejunojejunal intussusception, with no visible lead point. Spontaneous reduction was confirmed during exploratory laparoscopy. After lysis of adhesions, intraoperative peroral jejunoscopy was performed with the surgeons’ assistance. Endoscopy confirmed the absence of tumor, and bowel resection was avoided. No recurrence has been observed during 24 months of follow-up. Intraoperative endoscopy may provide additional reassurance for the absence of a lead point in cases where preoperative enteroscopy cannot be performed and no lead points can be identified on imaging.

Machine learning algorithms are effective in realizing the programming of robots that behave autonomously for various tasks. For example, reinforcement learning (RL) does not require supervision or data sets; the RL agent explores solutions by itself. However, RL requires a long learning time, particularly for actual robot learning situations. Transfer learning (TL) in RL has been proposed to address this limitation. TL realizes fast adaptation and decreases the problem-solving time by utilizing the knowledge of the policy, value function, and Q-function from RL. Taylor proposed TL using inter-task mapping that defines the correspondence between the state and action between the source and target domains. Inter-task mapping is defined based on human intuition and experience; therefore, the effect of TL may not be obtained. The difference in robot shapes for TL is similar to the cognition in the modification of human body composition, and automatic inter-task mapping can be performed by referring to the body representation that is assumed to be stored in the human brain. In this paper, body calibration is proposed, which refers to the physical expression in the human brain. It realizes automatic inter-task mapping by acquiring data modeled on a body diagram that illustrates human body composition and posture. The proposed method is evaluated in a TL situation from a computer simulation of RL to actual robot control with a multi-legged robot.

Introduction: Cervical ossification of the anterior longitudinal ligament (OALL) occasionally leads to dysphagia by the anterior osteophyte. A recent report explained that the dysphagia after an occipito-cervical fusion is caused by the narrowing of pharyngeal space due to the cranio-cervical malalignment. The purpose of this study was to evaluate the cranio-cervical alignment in patients with OALL complaining of the dysphagia. Subjects and methods: The subjects were 11 cases with complaining of dysphagia due to cervical OALL who underwent anterior cervical OALL resection and as control, age-matched 12 cases without dysphagia who have diffuse idiopathic skeletal hyperostosis in cervical spine. All subjects were male, and the mean age was 59.5 ± 9.1 years. The subjects were divided into two groups according to the symptoms of dysphagia (dysphagia, group A; control, group B). The O–C2 angle, C2–C7 angle, and the maximum thickness of OALL and the cranio-cervical alignment (pharyngeal inlet angle; PIA) and swallowing line (S-line) were measured before and after the operation on the lateral cervical radiogram at the sitting position. Results: Group A showed significantly large maximum thickness of OALL, small cervical range of motion, small O–C2 angle, large C2–C7 angle, and small PIA. The S-line crossed the anterior apex of cervical osteophyte in group A. After OALL resection, dysphagia had improved, PIA had increased, and the S-line uncrossed the apex of cervical vertebrae in all cases. Conclusion: The prevalence of dysphagia in patients with cervical OALL was influenced by the thickness of osteophyte, cervical mobility, and cranio-cervical alignment.

Short-chain fatty acids (SCFAs) produced by gastrointestinal microbiota regulate immune responses, but host molecular mechanisms remain unknown. Unbiased screening using SCFA-conjugated affinity nanobeads identified apoptosis-associated speck-like protein (ASC), an adaptor protein of inflammasome complex, as a noncanonical SCFA receptor besides GPRs. SCFAs promoted inflammasome activation in macrophages by binding to its ASC PYRIN domain. Activated inflammasome suppressed survival of Salmonella enterica serovar Typhimurium (S. Typhimurium) in macrophages by pyroptosis and facilitated neutrophil recruitment to promote bacterial elimination and thus inhibit systemic dissemination in the host. Administration of SCFAs or dietary fibers, which are fermented to SCFAs by gut bacteria, significantly prolonged the survival of S. Typhimurium–infected mice through ASC-mediated inflammasome activation. SCFAs penetrated into the inflammatory region of the infected gut mucosa to protect against infection. This study provided evidence that SCFAs suppress Salmonella infection via inflammasome activation, shedding new light on the therapeutic activity of dietary fiber. This study shows that short-chain fatty acids (SCFAs) bind to the inflammasome adaptor protein, apoptosis-associated speck-like protein (ASC). SCFAs thereby promote inflammasome activation in macrophages and protect against Salmonella infection via bacterial elimination in gut, shedding new light on the therapeutic activity of dietary fiber.

Purpose: Dropped head syndrome (DHS) is characterized by the passively correctable chin-on-chest deformity. The characteristic feature is emphasized in the cervical flexion position. The purpose of this study was to analyze the influence of cervical flexion on sagittal spinal alignment in patients with DHS. Methods: The study included 15 DHS subjects and 55 cervical spondylosis (CS) subjects as the control group. The following parameters were analyzed: cervical sagittal vertical axis (C-SVA), occipitoaxial angle (O–C2A), C2 slope (C2S), C2–C7 angle (C2–C7A), T1 slope (T1S), sagittal vertical axis, T1–T4 angle (T1–T4A), T5–T8 angle (T5–T8A), T9–T12 angle, lumbar lordosis, sacral slope, and pelvic tilt, in cervical flexion and neutral positions. Results: The values of C-SVA, O–C2A, C2S, and T1S were significantly different between CS and DHS at cervical neutral and flexion positions. C2–C7A showed significant difference in cervical neutral position, but the difference disappeared in flexion position. T1–T4A did not present a significant difference, but T5–T8A showed a difference in neutral and flexion positions. Conclusions: Malalignment of DHS extended not only to cervical spine but also to cranio-cervical junction and thoracic spine, except T1–T4. It is known that global sagittal spinal alignment is correlated with adjacent parameters, although in DHS the reciprocal change was lost from cranio-cervical junction to the middle part of thoracic spine at cervical flexion.

Purpose: The initial treatment of dropped head syndrome (DHS) is basically nonsurgical, but the mode of onset of DHS and efficacy of conservative treatment have not been fully clarified. Methods: The subjects were 38 DHS patients without neuromuscular disease (11 men and 27 women, average age 74.5 years). Cervical collar, physical therapy, and temporary medication for cervical pain were provided for all DHS patients. The following parameters were measured on lateral global spine standing radiographs: sagittal vertical axis (SVA), cervical sagittal vertical axis, C2–C7 angle, first thoracic slope, thoracic kyphosis, lumbar lordosis, sacral slope, pelvic tilt, and pelvic incidence. According to the mode of onset of DHS, the subjects were classified into acute-onset group (

Background and study aims Helicobacter pylori-associated nodular gastritis, which is associated with follicular lymphoid hyperplasia, is mainly recognized in the antrum. However, we have also observed nodularity-like appearance in the cardia. This study aimed to investigate the clinical significance of cardiac nodularity-like appearance in H. pylori-associated gastritis. Patients and methods Patients who underwent esophagogastroduodenoscopy and were evaluated for H. pylori infection for the first time were enrolled. A nodularity-like appearance in the cardia was defined as a miliary nodular appearance or scattered appearances of small circular whitish coloration. H. pylori infection was diagnosed according to serum anti-H. pylori antibody and the urea breath test or histology. Accuracy of the H. pylori infection diagnoses based on nodularity-like appearance were assessed. Results Among 265 patients, 42 patients (15.8 %) were diagnosed as positive for H. pylori. Cardiac nodularity-like appearance and antral nodularity were recognized in 25 and 15 patients, respectively. In accuracy of predicting H. pylori by cardiac nodularity-like appearance, specificity was 0.996, sensitivity was 0.571, positive predictive value was 0.960, negative predictive value was 0.925, and accuracy was 0.928. The sensitivity of cardiac nodularity-like appearance was significantly higher than that of antral nodularity (P = 0.0284). Conclusions Cardiac nodularity-like appearance had a high accuracy rate for H. pylori infection diagnosis. Cardiac nodularity-like appearance was found more frequently than antral nodularity.

Background: Malignant solitary fibrous tumor (MSFT) arising from the spinal cord is extremely rare and poorly understood mesenchymal neoplasms: only a few MSFT in the spinal canal has been described. We describe the clinical course of the patient with MSFT arising from the thoracic spinal cord. Case report: We describe the clinical course of the patient and the radiological and pathological findings of the tumor. The tumor had been resected by microscopic posterior approach and video-assisted thoracic surgery, but local recurrence was observed by MRI at 1-year follow-up period. No metastatic lesion was confirmed. Then, carbon ion radiotherapy (CIRT) was administered to the recurrent lesion. Local suppression has been observed for 40 months after irradiation. Conclusion: Dumbbell-shaped MSFT arising from thoracic spinal cord is a highly unusual presentation. CIRT might be effective for treatment of recurrent tumors.