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Background and Aim: Recently, the use of various endoscopic procedures performed under X-ray fluoroscopy guidance has increased. With the popularization of such procedures, diagnostic reference levels (DRLs) have been widely accepted as the global standard for various procedures with ionizing radiation. The Radiation Exposure from Gastrointestinal Fluoroscopic Procedures (REX-GI) study aimed to prospectively collect actual radiation exposure (RE) data and establish DRLs in gastrointestinal endoscopy units. In this post hoc analysis of the REX-GI study, we established DRLs for each disease site by analyzing cases of gastrointestinal enteral metallic stent placement., Methods: The REX-GI study was a multicenter, prospective observational study conducted to collect actual RE data during gastrointestinal enteral metallic stent placement. To establish DRL values for three disease sites, namely the esophagus, gastroduodenum, and colon, we examined fluoroscopy time (FT; min), number of X-ray images, air kerma at the patient entrance reference point ( K a,r ; mGy), and the air kerma-area product ( P KA ; Gy cm 2 ) during enteral metallic stent placement., Results: Five-hundred and twenty-three stenting procedures were performed. The DRL values of FT (min) and the number of X-ray images for the esophagus/gastroduodenum/colon were 9/16/18 min and 9/15/11 min, respectively. Furthermore, the DRL values of K a,r and P KA for each disease site were 43.3/120/124 mGy and 10.3/36.6/48.4 Gy cm 2 , respectively. Among the procedures, esophageal stents were significantly associated with the lowest values ( P  < 0.001)., Conclusion: The characteristics of RE vary according to disease site among gastrointestinal enteral metallic stent placements. Thus, it is desirable to set DRL values based on the disease site., (© 2023 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objectives: We surveyed and reported low protective equipment usage and insufficient knowledge among endoscopy-fluoroscopy departments in Japan in 2020. Two years later, we conducted a follow-up survey of doctors, nurses, and technologists in Japan., Methods: We conducted a questionnaire survey on radiation protection from May to June 2022. The participants were medical staff, including doctors, nurses, and radiological and endoscopy technicians in endoscopy-fluoroscopy departments. The questionnaire included 17 multiple-choice questions divided into three parts: background, equipment, and knowledge., Results: We surveyed 464 subjects from 34 institutions. There were 267 doctors (58%), 153 nurses (33%), and 44 technologists (9%). The rate of wearing a lead apron was 98% in this study. The rates of wearing a thyroid collar, lead glasses, and radiation dosimeter were 27%, 35%, and 74%, respectively. The trend of the protective equipment rate was similar to that of our previous study; however, radiation dosimetry among doctors was still low at 58%. The percentage of subjects who knew the radiation exposure (REX) dose of each procedure was low at 18%. Seventy-six percent of the subjects attended lectures on radiation protection, and 73% knew about the three principles of radiation protection; however, the concept of diagnostic reference levels was not well known (18%). Approximately 60% of the subjects knew about the exposure dose increasing cancer mortality (63%) and the 5-year lens REX limit (56%)., Conclusions: There was some improvement in radiation protection equipment or education, but relatively little compared to the 2020 survey of endoscopy departments., Competing Interests: The author Mamoru Takenaka is an AE of Digestive Endoscopy. The author Ichiro Oda is an AE of Digestive Endoscopy. The author Yousuke Nakai is an AE of Digestive Endoscopy. The author Seiichiro Abe is an AE of DEN Open. The rest of the authors declare no conflict of interest., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Limitations of gait function persist in some patients with knee osteoarthritis after total knee arthroplasty. This study aimed to identify preoperative muscle composition variables of the operated limb associated with postoperative gait function., Methods: Longitudinal data from 45 patients who underwent unilateral primary total knee arthroplasty were retrospectively analyzed. Timed Up-and-Go test and gait speed were measured preoperatively and at 3 and 6 months postoperatively. Preoperative muscle composition in the glutei medius and minimus, the quadriceps, the hamstrings, and combination of the hamstrings and quadriceps were evaluated by computed tomography. The area ratio of the individual muscle composition to the total muscle was calculated. The factors associated with Timed Up-and-Go test and gait speed were identified using stepwise regression analysis., Results: Shorter Timed Up-and-Go test and faster gait speed at each time point correlated with higher lean muscle mass area of the total hamstrings, higher area ratio of lean muscle mass to the total hamstrings or to combination of the hamstrings and quadriceps, and lower area ratio of low density lean tissue or intramuscular adipose tissue to the total hamstrings. Shorter Timed Up-and-Go test at each time point also correlated with higher combined area of lean muscle mass of the hamstrings and quadriceps. Faster gait speed at each time point additionally correlated with lower area ratio of intramuscular fat to the total hamstrings and lower area ratio of lean tissue mass or intramuscular adipose tissue to combination of the hamstrings and quadriceps. Regression analysis using the significant muscle composition variables revealed that the area ratio of lean muscle mass to the total hamstrings was the only predictor of Timed Up-and-Go test and gait speed after operation., Conclusions: Preoperative area ratio of ipsilateral lean muscle mass to the total hamstrings could predict gait function after total knee arthroplasty., Competing Interests: Declaration of competing interest None., (Copyright © 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Diagnostic reference levels (DRLs) are required to optimize medical exposure. However, data on DRLs for interventional fluoroscopic procedures are lacking, especially in gastroenterology. This study aimed to prospectively collect currently used radiation doses and help establish national DRLs for fluoroscopy-guided gastrointestinal procedures in Japan., Methods: This multicentre, prospective, observational study collected actual radiation dose data from endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasound (EUS), balloon-assisted enteroscopy (BAE), enteral metallic stent placement, and enteral tube placement from May 2019 to December 2020. The study outcomes were fluoroscopy time (FT: min), air kerma at the patient entrance reference point (K a,r : mGy), air kerma area product (P KA : Gycm 2 ), and radiation dose rate (RDR: mGy/min). Additionally, the basic settings of fluoroscopy equipment and the factors related to each procedure were investigated. This study was registered in the UMIN Clinical Trial Registry (UMIN 000036525)., Findings: Overall, 12959 fluoroscopy-guided gastrointestinal procedures were included from 23 hospitals in Japan. For 11162 ERCPs, the median/third quartile values of K a,r (mGy), P KA (Gycm 2 ), and FT (min) were 69/145 mGy, 16/32 Gycm 2 , and 11/20 min, respectively. Similarly, these values were 106/219 mGy, 23/41 Gycm 2 and 17/27 min for 374 interventional EUSs; 53/104 mGy, 16/32 Gycm 2 and 10/15 min for 523 metallic stents; 56/104 mGy, 28/47 Gycm 2 , and 12/18 min for 599 tube placements; and 35/81 mGy, 16/43 Gycm 2 and 7/15 min for 301 BAEs, respectively. For the overall radiation dose rate, the median/third quartile values of RDR were 5.9/9.4 (mGy/min). The RDR values at each institution varied widely., Interpretation: This study reports the current radiation doses of fluoroscopy-guided gastrointestinal procedures expressed as DRL quantities. This will serve as a valuable reference for national DRL values., Funding: This work was supported by a clinical research grant from the Japanese Society of Gastroenterology., Competing Interests: None of the authors has any competing interests arising from this research., (© 2021 The Author(s).)

Aims: This study aimed to evaluate sagittal spinopelvic alignment (SSPA) in the early stage of rapidly destructive coxopathy (RDC) compared with hip osteoarthritis (HOA), and to identify risk factors of SSPA for destruction of the femoral head within 12 months after the disease onset., Methods: This study enrolled 34 RDC patients with joint space narrowing > 2 mm within 12 months after the onset of hip pain and 25 HOA patients showing femoral head destruction. Sharp angle was measured for acetabular coverage evaluation. Femoral head collapse ratio was calculated for assessment of the extent of femoral head collapse by RDC. The following parameters of SSPA were evaluated using the whole spinopelvic radiograph: pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), sagittal vertical axis (SVA), thoracic kyphosis angle (TK), lumbar lordosis angle (LL), and PI-LL., Results: The HOA group showed higher Sharp angles compared with the RDC group. PT and PI-LL were higher in the RDC group than the HOA group. SS and LL were lower in the RDC group than the HOA group. No difference was found in PI, SVA, or TK between the groups. Femoral head collapse ratio was associated with PT, SS, SVA, LL, and PI-LL. A PI-LL > 20° and a PT > 30° correlated with greater extent of femoral head destruction by RDC. From regression analysis, SS and SVA were significantly associated with the femoral head collapse ratio within 12 months after disease onset., Conclusion: Compared with HOA, RDC in the early stage correlated with sagittal spinopelvic malalignment. SS and SVA may partially contribute to the extent of femoral head destruction by RDC within 12 months after the onset of hip pain. The present study indicates a potential role of SSPA assessment in identification of RDC patients at risk for subsequent bone destruction. Cite this article: Bone Jt Open  2022;3(1):77-84.

Introduction: This study investigated the efficacy and complications of preoperative embolization for spinal metastatic tumors, focusing on the etiology of post-embolization paralysis., Methods: We retrospectively reviewed the data of 44 consecutive patients with spinal metastases treated between September 2012 and December 2020. Intraoperative blood loss and postoperative transfusion requirement were compared between the embolization (+) and (-) groups. Complications associated with embolization were reviewed., Results: Overall, 30 patients (68%) underwent preoperative embolization. All the patients in both groups underwent palliative posterior decompression and fusion. The mean intraoperative blood loss in the overall population was 359 ml (range, minimum-2190 ml) and was 401 ml and 267 ml in the embolization (+) and embolization (-) groups, respectively. Four patients (9%) (2 patients from each group) required blood transfusion. There were no significant between-group differences in blood loss and blood transfusion requirements. All 7 patients with hypervascular tumors were in the embolization (+) group. Two patients experienced muscle weakness in the lower extremities on days 1 and 3 after embolization. There were metastases in T5 and T1-2, and magnetic resonance imaging after embolization showed slight exacerbation of spinal cord compression. The patients showed partial recovery after surgery., Conclusions: With the predominance of hypervascular tumors in the embolization (+) group, preoperative embolization may positively affect intraoperative bleeding. Embolization of metastatic spinal tumors may pose a risk of paralysis. Although the cause of paralysis remains unclear, it might be due to the aggravation of spinal cord compression. Considering this risk of paralysis, we advocate performing surgery as soon as possible after embolization., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest., (Copyright © 2022 by The Japanese Society for Spine Surgery and Related Research.)

Background and Aims: It is essential for endoscopists, technologists, and nurses to understand radiation protection. However, protective equipment usage is still low, and there is little awareness of radiation protection in practice., Methods: We conducted a questionnaire survey on radiation protection from January to February 2020. The participants were medical staff, including medical doctors, nurses, and radiological and endoscopy technician in endoscopy-fluoroscopy departments. The questionnaire included 14 multiple-choice questions divided among three parts: background, equipment, and knowledge., Results: We surveyed a total of 282 subjects from 26 institutions. There were 168 medical doctors (60%), 90 nurses (32%), and 24 technologists (9%). Although almost all staff members (99%) always wore a lead apron, only a few wore a thyroid collar (32%) and lead glasses (21%). The rate of wearing a radiation dosimeter was insufficient (69%), especially among doctors (52%). A few subjects knew the radiation exposure dose of each procedure (15%), and slightly over half had attended lectures on radiation protection (64%) and knew about the three principles of radiation protection (59%). Protection adherence did not differ by years of experience, knowledge of fluoroscopy, awareness of radiation exposure doses, or attendance at basic lectures on radiation protection. However, medical doctors who were aware of the radiation exposure dose of each procedure were significantly more likely to wear dosimeters than those who were not (p = 0.0008)., Conclusion: Medical staff in endoscopy departments in Japan do not have enough radiation protection equipment or education., Competing Interests: The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper., (© 2021 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Objective: Previous reports have demonstrated that patients with end-stage rapidly progressive osteoarthritis of the hip (RPOH) show significantly higher serum levels of bone turnover markers than those with osteoarthritis (OA). However, the characteristics of bone turnover markers in the early stage of RPOH remain unclear. This study aimed to elucidate the association of bone turnover markers with disease progression in the early stage of RPOH., Methods: This study included 29 postmenopausal female patients with joint space narrowing >2 mm demonstrated on a series of radiographs and computed tomography within 1 year following the onset of hip pain. The study also included 9 postmenopausal female patients with hip OA secondary to developmental dysplasia showing femoral head destruction. Cortical thickness index (CTI) associated with bone mineral density of the hip was analyzed. Serum concentrations of tartrate-resistant acid phosphatase-5b (TRACP-5b) and bone alkaline phosphatase (BAP) were evaluated., Results: RPOH was classified into two types on the basis of the absence (type 1, n=13) or presence (type 2, n=16) of subsequent destruction of the femoral head within 1 year following disease onset. TRACP-5b and BAP significantly increased in RPOH type 2 compared with type 1 and OA. Receiver operating characteristic curve analyses indicated that TRACP-5b and BAP could differentiate RPOH type 2 from type 1 within 1 year following the onset. CTI showed no difference among the RPOH types 1 and 2 and OA., Conclusion: High serum levels of bone turnover markers may be associated with destruction of the femoral head in the early stage of RPOH.

Lenvatinib is a standard molecular targeted agent for the first-line treatment of unresectable hepatocellular carcinoma. Here, we report a case of colitis induced by Lenvatinib treatment in a patient with hepatocellular carcinoma. A 78-year-old man previously treated with Lenvatinib for unresectable hepatocellular carcinoma was admitted to our hospital complaining of right lateral abdominal pain without diarrhea. Our endoscopic findings showed multiple ulcers and erosions on his ascending colon, and he was diagnosed with colitis induced by Lenvatinib treatment. After the discontinuation of Lenvatinib, his colitis improved, and he resumed Lenvatinib at a lower dose. Colitis is a rare adverse event of Lenvatinib, and this is the first detailed report of colitis induced by Lenvatinib with endoscopic findings.

Background: White globe appearance (WGA) is a small white lesion with a globular shape identified during magnifying endoscopy with narrow-band imaging. However, the association between WGA and synchronous multiple gastric cancer (SMGC) remains unclear., Methods: Consecutive patients who underwent endoscopic submucosal dissection for gastric cancer (GC) between July 2013 and April 2015 at our institution were eligible for this study. We excluded patients with a history of gastric tumor or gastrectomy. Patients who had more than 2 GCs in their postoperative pathological evaluation were classified as SMGC-positive, and patients who had at least 1 WGA-positive GC were classified as WGA-positive patients. The primary outcome was a comparison of the prevalence of WGA in patients classified as SMGC-positive and SMGC-negative. Univariate and multivariate analyses were performed using the following variables: WGA, age, sex, atrophy, and Helicobacter pylori ( H. pylori ) status., Results: There were 26 and 181 patients classified as SMGC-positive and SMGC-negative, respectively. Univariate analysis revealed that WGA-positive classification (50% vs. 23%, P=0.008) and male sex (88% vs. 66%, P=0.02) were significant factors associated with SMGC classification, while age ≥65 years (81% vs. 81%, P>0.99), severe atrophy (46% vs. 46%, P>0.99), and H. pylori positivity (69% vs. 65%, P=0.8) were not. In the multivariate analysis, only WGA-positive classification (odds ratio 2.78, 95% confidence interval 1.16-6.67; P=0.02) was a significant independent risk factor for SMGC., Conclusions: Our exploratory study showed the possibility of WGA as a predictive factor for SMGC. In cases of WGA-positive gastric cancer, careful examination might be needed to diagnose SMGC., Competing Interests: Conflict of Interest: None, (Copyright: © 2021 Hellenic Society of Gastroenterology.)

Colonic diverticular bleeding often recurs and requires hospital readmission. This study aimed to examine the relationship between the rate of readmission and the number of hospitalizations due to colonic diverticular bleeding. We retrospectively studied 98 patients first admitted between January 2008 and July 2017 for the treatment of colonic diverticular bleeding. We investigated the subsequent number of hospitalizations due to colonic diverticular bleeding and classified the patients into 3 groups:those admitted for the first time (first group), those admitted for the second time (second group), and those admitted for the third time or later (third group). Generally, the readmission rate increased as the number of hospitalizations increased (P<0.01). The 1-year readmission rates were 11.6%, 23.2%, and 34.2% in the first, second, and third groups, respectively. The 2-year readmission rates were 15.1%, 50.1%, and 62.4% in the first, second, and third groups, respectively. The 3-year readmission rates were 21.7%, 50.1%, and 74.9% in the first, second, and third groups, respectively. Thus, the number of hospitalizations due to colonic diverticular bleeding could be a predictive factor for readmission. We also classified the patients into 2 additional groups:those who had been readmitted (readmission group) and those who had not (no readmission group). Furthermore, we examined background and therapeutic factors, and found hypovolemic shock on admission to be an independent risk factor (odds ratio 14.1). Preventive treatments for such high-risk patients should be considered.

Objective: This study aimed to characterize the process of disease progression in the early stage of rapidly progressive osteoarthritis of the hip (RPOH) and clarify its association with potential pathological factors of RPOH., Methods: This monocentric retrospective study included 41 female patients who met the criteria for RPOH, chondrolysis >2 mm during 12 months from the onset of hip pain based on a series of radiographs and computed tomography. This study also included 9 female patients with osteoarthritis secondary to developmental dysplasia of the hip (DDH) who demonstrated chondrolysis >2 mm during 12 months from the onset of hip pain. Cortical thickness index (CTI) correlated with bone mineral density of the hip, pelvic tilt, and serum concentrations of matrix metalloproteinase (MMP)-3 were analyzed., Results: RPOH was classified into two types based on the absence (type 1, n=17) and presence (type 2, n=24) of subsequent femoral head destruction within 12 months after the onset of hip pain. MMP-3 significantly increased in RPOH type 2 compared with type 1 and DDH. Increased posterior pelvic tilt was found in RPOH type 2 compared with DDH. Logistic regression and receiver operating characteristic curve analyses indicated that MMP-3 may be associated with differentiation between RPOH types 1 and 2. No difference was found in the CTI between the RPOH types and DDH., Conclusion: Disease progression of RPOH during 12 months after the onset of hip pain could be classified into two distinct types based on the absence (type 1) and presence (type 2) of femoral head destruction in association with MMP-3 and pelvic tilt as biological and mechanical factors, respectively. MMP-3 may be helpful to differentiate these two types in the early stage of RPOH.

The patient, a man in his 80s, presented with diarrhea following one year of treatment for non-small cell lung cancer with Nivolumab. CT results showed discontinuous wall thickening of the large bowel and cholangitis. Blood and stool culture tests ruled out immune-related adverse events and identified Edwardsiella tarda;bacterial colitis was diagnosed in the patient. This case confirmed that basic examination should not be neglected, and culture tests should be performed.

Background: The aim of the study was to clarify the frequency of colorectal neoplasm (CRN) complicating superficial esophageal squamous cell carcinoma (ESCC) and the need for colonoscopy., Methods: We retrospectively reviewed 101 patients who had undergone initial endoscopic resection (ER) for superficial ESCC. Control group participants were age- and sex-matched asymptomatic subjects screened at our hospital over the same period of time. Advanced adenoma was defined as an adenoma ≥10 mm, with villous features, or high-grade dysplasia. Advanced CRN referred to advanced adenoma or cancer. We measured the incidence of advanced CRN in superficial ESCC and controls, and we compared the characteristics of superficial ESCC patients with and without advanced CRN., Results: In the superficial ESCC group, advanced CRNs were found in 17 patients (16.8%). A history of smoking alone was found to be a significant risk factor of advanced CRN [odds ratio 6.02 (95% CI 1.30-27.8), P=0.005]., Conclusion: The frequency of synchronous advanced CRN is high in superficial ESCC patients subjected to ER. Colonoscopy should be highly considered for most patients who undergo ER for superficial ESCC with a history of smoking, and is recommended even in superficial ESCC patients.

Background and Aim: White globe appearance (WGA) is a small white lesion with a globular shape that can be identified by magnifying endoscopy with narrow-band imaging (M-NBI). WGA was recently reported as a novel endoscopic marker that can differentiate between gastric cancer (GC) and low-grade adenoma. However, the usefulness of WGA for differentiating GC from non-cancerous lesions (NC), including those of gastritis, is unknown., Methods: To compare the prevalence of WGA in GC and NC, we carried out a prospective study of 994 patients undergoing gastroscopy. All patients were examined for target lesions that were suspected to be GC. When a target lesion was detected, the presence or absence of WGA in the lesion was evaluated using M-NBI, and all target lesions were biopsied or resected for histopathological diagnosis. Primary endpoint was a comparison of WGA prevalence in GC and NC. Secondary endpoints included WGA diagnostic performance for diagnosing GC., Results: A total of 188 target lesions from 156 patients were analyzed for WGA, and histopathological diagnoses included 70 cases of GC and 118 cases of NC. WGA prevalence in GC and NC was 21.4% (15/70) and 2.5% (3/118), respectively (P < 0.001). WGA diagnostic accuracy, sensitivity, and specificity for detecting GC were 69.1%, 21.4%, and 97.5%, respectively., Conclusions: WGA prevalence in GC is significantly higher than that in NC. Because WGA is highly specific for GC, the presence of WGA is useful to diagnose GC., (© 2015 Japan Gastroenterological Endoscopy Society.)

INUBUSHI SEIYAKU, a Japanese pharmaceutical company established in 1807, manufactures KEISHIN-TAN. This is an original drug developed by the company, and consists of 14 exotic natural medicines, spikenard, oriental bezoar, musk, agarwood, etc. It has been used for adjusting the autonomic nervous system and physical conditions. We studied the original methods of the traditional quality management techniques handed down within INUBUSHI SEIYAKU in selecting the appropriate spikenard (Nardostachys chinensis) for medicinal use. Currently, spikenards are mainly used as incense rather than medicine. KEISHIN-TAN is a rare case in that the bulk powder of the spikenards is used for pharmaceutical products in Japan. We examined the morphological characteristics and made an analysis of the component of spikenards selected by traditional methods. The raw material of the spikenards was purchased from the Japanese market, and was classified into two categories-superior, fit for medicinal use and defective, to be discarded-by traditional methods of INUBUSHI SEIYAKU. The methods of the characterization of the spikenard by INUBUSHI SEIYAKU were investigated. As a result, only thick spikenard roots over 2.0 cm in length and approximately 0.5 cm in diameter were found to be used, and the total weight of the superior was only 15% of the raw material. By comparing the weights of hexane extracts and GC-MS analyses, the content of calarene--main sedative compound in spikenards--in the superior material was 2.8 times higher than the raw material and 4.3 times higher than the defective material. The ways to devise how to enhance the pharmacological effects of spikenards may be contained in this method. These results revealed the traditional spikenard selection criteria, and may show the indications of using spikenard or its compounds for medicinal purposes.

Background/aims: Artificial ulcers remain a major complication after Endoscopic submucosal dissection (ESD). The development of more effective treatment regimen for this ulcer is required than the use of proton pump inhibitor (PPI) alone., Methodology: Patients with ESD-derived artificial ulcers were randomly assigned to two groups: a group of patients who received rabeprazole 20 mg daily for 8 weeks (PPI group) and a group of patients who received a combination of rebamipide 300 mg daily for 8 weeks and rabeprazole 20 mg dairy for the first 4 weeks (reb+PPI group). The area reduction ratio and healing status of ulcers were evaluated endoscopically on postoperative 7, 28 and 56 days., Results: The overall ulcer area reduction ratio was higher in the reb+PPI group than in the PPI group, especially at an early stage. The ratio of progression to the H1 stage in the reb+PPI group was significantly higher than that in the PPI group, especially at an early stage., Conclusions: Treatment with 8 weeks of rebamipide plus the first 4 weeks of PPI demonstrated a reduction ratio of artificial ulcers superior to that with 8 weeks of PPI mono-therapy. This combination treatment is, therefore, one of the candidate treatment strategies against ESD-derived artificial ulcers.

Toll‑like receptor activation intitially recruits the myeloid differentiation primary response gene (88) (MyD88) protein. A polymorphism *1244 A>G (rs7744) in the 3'‑untranslated region of MyD88 has been identified. In the present study, the association of this polymorphism with ulcerative colitis (UC) was investigated. The population studied comprised 922 individuals, including patients with UC (UC cases) and without (controls). Genotyping of rs7744 was performed by PCR single-strand conformation polymorphism and the rs7744 G allele frequencies in the controls and UC cases were 32.8 and 43.5%, respectively (P<0.0001). The results showed that the genotype frequency of the AA homozygote was significantly lower and that of the GG homozygote was significantly higher in the UC cases compared with those in the controls (P=0.0012 for both groups). The rs7744 minor allele variants were significantly associated with susceptibility to UC as indicated by dominant and recessive genetic models. The minor allele variants were associated with an increased risk for UC in the male individuals but not the female individuals. The rs7744 was also associated with a non‑continuous phenotype of UC and steroid unused/independent UC. This minor allele homozygote was associated with the disease severity of UC, hospitalization and response to steroid treatment. The results of the present study provided evidence that MyD88 polymorphism rs7744 was significantly associated with the development of UC and that this polymorphism may be associated with the response to treatment therapies for UC.

In the present study, we report an association between gastric cancer and polymorphisms in NFKB1 (rs28362941 and rs78696119). We employed the PCR-SSCP method to detect gene polymorphisms in 479 gastric cancer cases and 880 controls. The rs28362941 del/del homozygote was significantly associated with gastric cancer development; in particular it was closely associated with diffuse type gastric cancer. The rs78696119 GG homozygote was also associated with the diffuse type of gastric cancer. In young subjects, both polymorphisms were significantly associated with the development of gastric cancer. In addition, both polymorphisms were related to tumor progression such as tumor invasion and lymph node metastasis. The inflammatory cell infiltration into non-cancerous gastric mucosa was greater in the subjects with the rs28362491 del/del or rs78696119 GG genotype when compared to those with the other genotypes. In conclusion, functional polymorphisms of NFKB1 are associated with an increased risk of gastric cancer; in particular they are closely associated with the development of diffuse type of gastric cancer via severe gastric inflammation. These polymorphisms also appear to be associated with gastric cancer progression.

Background: Aberrant methylation patterns in CpG island are known to be influential in gene silencing. Histamine plays important physiological roles in the upper gastrointestinal tract and acts via the H2 receptor. We report an investigation into the effect of HRH2 promoter polymorphism (rs2607474 G > A) on the methylation of DAPK and CDH1., Methods: Non cancerous gastric mucosa samples were obtained from 115 subjects with gastric cancer (GC) and 412 non-cancer subjects (non-GC). Methylation status of genes was determined by MSP. The genotyping of rs2607474 was performed by PCR-SSCP., Results: Methylation of DAPK and CDH1 was observed in 296 and 246 subjects, respectively. The frequency of CDH1 methylation in the subjects with GC was significantly lower in cancer lesion than in non cancerous mucosa, whereas that of DAPK methylation was not different. The allelic distribution of rs2607474 was 401GG, 119GA and 7AA. The GG homozygote was associated with a significantly increased risk for methylation of both DAPK and CDH1 (p < 0.0001 and p = 0.0009, respectively). In the non-GC subjects or more than 60 years of age, GG homozygote was more closely associated with both DAPK and CDH1 methylation. However, this genotype did not show an increased risk for the development of methylation of both genes in patients with GC. In H. pylori negative subjects, GG homozygote showed an increased risk for the methylation of both DAPK and CDH1 (p = 0.0074 and p = 0.0016, respectively), whereas this genotype was associated with an increased risk for the development of DAPK methylation in H. pylori positive subjects (p = 0.0018). In addition, in subjects older than 60 years of age, atrophy and metaplasia scores were significantly higher in the GG homozygote (p = 0.011 and p = 0.039, respectively) and a significant correlation was observed between age and atrophy or metaplasia., Conclusions: Our results suggest that rs2607474 GG homozygote confers a significantly increased risk for age- and inflammation-related DAPK and CDH1 methylation.

Aim: To clarify the association between a polymorphism -449 C>G (rs72696119) in 5'-UTR of NFKB1 with ulcerative colitis (UC)., Methods: The studied population comprised 639 subjects, including patients with UC (UC cases, n = 174) and subjects without UC (controls, n = 465). We employed polymerase chain reaction-single strand conformation polymorphism to detect the gene polymorphism., Results: The rs72696119 G allele frequencies in controls and UC cases were 33.4% and 38.5%, respectively (P = 0.10). Genotype frequency of the GG homozygote in UC cases was significantly higher than that in controls (P = 0.017), and the GG homozygote was significantly associated with susceptibility to UC [odds ratio (OR), 1.88; 95%CI, 1.13-3.14]. In male subjects, the GG homozygote was associated with an increased risk for UC (OR, 3.10; 95%CI, 1.47-6.54; P = 0.0053), whereas this association was not found in female subjects. In addition, the GG homozygote was significantly associated with the risk of non-continuous disease (OR, 2.06; 95%CI, 1.12-3.79; P = 0.029), not having total colitis (OR, 2.40; 95%CI, 1.09-3.80, P = 0.040), disease which developed before 20 years of age (OR, 2.80; 95%CI, 1.07-7.32, P = 0.041), no hospitalization (OR, 2.28; 95%CI, 1.29-4.05; P = 0.0090) and with a maximum of 8 or less on the UCDAI score (OR, 2.45; 95%CI, 1.23-4.93; P = 0.022)., Conclusion: Our results provide evidence that NFKB1 polymorphism rs72696119 was significantly associated with the development of UC. This polymorphism influences the susceptibility to and pathophysiological features of UC.

Background: The role of genetics in the susceptibility to functional dyspepsia (FD) remains unclear. We attempted to clarify the association between FD and polymorphisms in SLC6A4. In addition, rs5981521 (C>T) in the pri-microRNA 325 (pri-miR-325) coding region was also investigated., Methods: The study was performed in 395 subjects (172 with no upper abdominal symptoms and 223 with FD, including medication-resistant FD). We employed a polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method to detect gene polymorphisms., Results: Neither SLC6A4 -185 A>C nor *463 G>T was associated with susceptibility to FD. The number of rs5981521 T alleles was significantly correlated with an increased risk for FD (odds ratio [OR] 1.45, 95 % confidence interval [CI] 1.05-1.98; p = 0.022) and the TT homozygote was more closely associated with the risk for FD (OR 3.01, 95 % CI 1.41-6.42; p = 0.0043). The TT homozygote also had significantly increased risks for both the epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) subtypes of FD (OR 3.04, 95 % CI 1.25-7.42; p = 0.014 and OR 3.05, 95 % CI 1.14-8.13; p = 0.026, respectively). In addition, Helicobacter pylori-negative TT homozygotes had a greater risk for FD (OR 8.37, 95 % CI 1.78-39.5; p = 0.0072). In subjects with the SLC6A4 5'-untranslated region (UTR) wild homozygote, the number of rs5981521 T alleles was significantly correlated to an increased risk for FD (OR 1.45, 95 % CI 1.03-2.04, p = 0.033). Of note, in subjects who were SLC6A4 3'-UTR mutant carriers, the number of rs5981521 T alleles was also significantly correlated with an increased risk for FD (OR 2.07, 95 % CI 1.08-3.98; p = 0.029)., Conclusions: Our results suggest that the genetic polymorphism pri-miR-325 is associated with FD and interacts with SLC6A4 polymorphisms in increasing susceptibility to FD in Japanese.

Background & Aim: The important role of IL-17 in inflammatory response to Helicobacter pylori (H. pylori) colonization has been indicated. We investigated the associations between gastro-duodenal diseases and polymorphisms of IL17A (rs2275913 G>A) and IL17F (rs763780 T>C)., Methods: The study was performed in 548 subjects (363 controls and 185 peptic ulcer cases). The multiplex PCR-SSCP method was used to detect gene polymorphisms., Results: Overall, number of rs2275913 A allele was significantly associated with an increased risk for peptic ulcer (OR, 1.50; 95%CI, 1.11-2.01; p=0.0082). The frequency of rs2275913 GA+AA genotype was also significantly higher in ulcer cases than controls (OR, 1.72; 95%CI, 1.09-2.72; p=0.020). The rs2275913 GA+AA genotype conferred an increased risk for the severity of gastric mucosal atrophy in subjects younger than 60 years (OR, 2.83; 95%CI, 1.14-7.04; p=0.025). Both atrophy and metaplasia were increased with age in rs2275913 GA+AA genotype. In NSAIDs/aspirin users, number of rs2275913 A allele was associated with an increased risk for a peptic ulcer (OR, 3.98; 95%CI, 1.48-10.7; p=0.0061). There was no association of rs763780 with the development of peptic ulcer., Conclusions: Our results provide the evidence that rs2275913 is associated with an increased risk for peptic ulcer and the severity of the gastric mucosal atrophy in comparatively younger subjects. In addition, this allele is also associated with the increased risk for peptic ulcer in NSAIDs/aspirin users.

Histamine plays important physiological roles in the upper gastrointestinal tract and acts via the H2 receptor. The -1018 G>A (rs2067474) in an enhancer element of the promoter and non-synonymous rs79385261 (Asn46Thr) were identified in HRH2. We attempted to clarify the associations of these polymorphisms with gastric carcinogenesis. The study was performed in 321 patients with gastric cancer and 599 subjects with no evidence of gastric malignancies on upper gastroduodenal endoscopy. The genotypes were determined using a one-tube multiplex PCR-SSCP method. The degree of gastritis was assessed in 496 subjects and serum pepsinogen (PG) I/II levels were measured in 124 subjects without gastric cancer. The minor allele of Asn46Thr could not be detected. The frequencies of the -1018 A allele in the non-GC and GC groups were 13.5% and 8.26%, respectively (p=0.00077). Overall, -1018 GG homozygotes had an increased risk for developing gastric cancer (OR 1.68; 95% CI 1.17-2.42; p=0.0052), especially intestinal type cancer (OR 1.94; 95% CI 1.23-3.08; p=0.0047). In subjects aged >60 years, the adjusted risk for gastric cancer among individuals who were -1018 GG homozygotes was 1.87 (range 1.19-2.93; p=0.0065) compared with A carriers. In the gastric cancer cases located in the antrum and at comparative advanced stage, -1018 GG homozygosity was a significantly increased risk factor. In subjects >60 years, the metaplasia score was significantly higher in -1018 GG homozygotes than A carriers. Both atrophy and metaplasia scores were significantly increased with age only in -1018 GG homozygotes. The PG I/II ratio was significantly decreased in H. pylori positive GG homozygotes than negative GG homozygotes and positive A carriers. Our results suggest that -1018 GG homozygosity of HRH2 may be associated with the severity of gastric mucosal atrophy. This genotype has an increased risk for the subsequent development of gastric cancer, especially intestinal type, at advanced age.

We report an association between gastric cancer (GC) and polymorphisms in IL17A, rs2275913 (-197 G > A), rs3748067 (*1249 C > T), and pri-miR-938, rs2505901 (T > C). We employed the multiplex PCR-SSCP method to detect gene polymorphisms in 337 GC cases and 587 controls. The minor allele frequency of rs2275913 was significantly higher, and those of rs3748067 and rs2505901 significantly lower, in GC cases than controls. The rs2275913 AA homozygote was associated with an increased risk (OR, 2.38; 95%CI, 1.63-3.46; p < 0.0001) for the development of both intestinal and diffuse types of GC. The rs3748067 T polymorphism was associated with a decreased risk for intestinal GC (OR, 0.511; 95%CI, 0.272-0.962; p = 0.037), whereas rs2505901 C locus carried a decreased risk overall for GC (OR, 0.733; 95%CI, 0.545-0.985; p = 0.039). In addition, rs3748067 T allele was inversely correlated with lymph node metastasis. Our results suggest that polymorphisms in both IL17A and pri-miR-938 contribute to cancer risk susceptibility and therefore can affect the development of gastric cancer., (Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Objective: Sonazoid is a new second-generation microbubble contrast for ultrasonography. In this pilot study, the diagnostic role of contrast-enhanced harmonic imaging endoscopic ultrasonography (CH-EUS) with Sonazoid was prospectively evaluated in preoperative T-staging of pancreaticobiliary malignancies., Patients and Methods: Patients with suspected pancreaticobiliary malignancies underwent CH-EUS by a single examiner. After the lesions were observed carefully with conventional harmonic imaging EUS (H-EUS), CH-EUS was performed with intravenous injection of Sonazoid. A reviewer who was blinded reviewed the recordings of H-EUS and CH-EUS and assessed the T-staging. The accuracy of H-EUS and CH-EUS for T-staging was compared to the results of surgical histopathology in patients who underwent surgery., Result: Twenty-six patients underwent surgical resection and could be included in the study. The final diagnosis were pancreatic cancer in 11, bile duct cancer in 7, gallbladder cancer in 4 and ampullary cancer in 4. The overall accuracy of H-EUS and CH-EUS for T-staging were 69.2 (18/26) and 92.4% (24/26), respectively (p < 0.05). There were disagreement in six cases between H-EUS and CH-EUS. CH-EUS staged correctly in all of these six cases, whereas H-EUS misdiagnosed the depth of invasion in one case of gallbladder cancer and one case of ampullary cancer, and invasion of portal vein in two cases of pancreatic cancer and two cases of bile duct cancer., Conclusion: The depth of invasion of biliary cancer and vascular invasion of pancreatic and biliary cancer could be demonstrated more clearly with CH-EUS compared to H-EUS. CH-EUS has the potential to improve the diagnostic accuracy of preoperative T-staging of pancreaticobiliary malignancies.

Background and Aim: A new argon plasma coagulation (APC) system was developed to improve the conduction characteristics of existing systems and to achieve a true non-contact procedure. We evaluated the new system in an ex vivo experiment and in two different clinical cases., Methods: Swine gastric walls were cauterized at various current settings and time intervals. The diameter and penetration depth of the cauterized areas were measured. We also describe the use of this method to treat patients with gastric hemorrhagic hereditary telangiectasias and a mucosal gastric cancer., Results: The ex vivo study revealed an improved maintenance of current conduction and greater control of the extent and penetration depth of the cauterization effects on tissue using the new APC system. In the clinical cases, hemorrhagic telangiectasias and an early stage gastric cancer were treated successfully without relapse using the new system., Conclusions: Improved current conduction and controllability of cauterization corresponding to emission time were demonstrated for the new APC. The new system allows expeditious superficial cauterization of a wide area without any contact with tissue. The therapeutic effect appeared favorable compared with previous APC devices for gastrointestinal applications.

Background: A newly developed narrow-band imaging (NBI) system, which uses modified optical filters, can yield clear images of microvessels and surface structure in gastric and colonic diseases. In the present study, we investigated the ability of magnifying endoscopy with NBI (MENBI) to diagnose and differentiate between benign and malignant ampullary tumors., Methods: Fourteen patients, whose ampullas were noted to be significantly enlarged or protruding with conventional endoscopy, were enrolled in the study. Specimens, which were obtained by forceps biopsy, endoscopic papillectomy, and/or surgery, were retrieved for histopathological examination. The correlation between MENBI images and histopathological findings was investigated. MENBI findings were classified as I, oval-shaped villi; II, pinecone/leaf-shaped villi; or III, irregular/nonstructured. In addition, tortuous, dilated, and network-like vessels noted on the ampullary lesions with MENBI were defined as abnormal vessels., Results: In 6 of 14 patients, the ampullary changes were proven to be inflammatory in forceps biopsy specimens, without any evidence of malignancy after more than 1 year of follow-up. In five patients, ampullary lesions were treated by endoscopic papillectomy, and in three, by pancreatoduodenectomy. All adenomas and adenocarcinomas had type II and/or type III surface structures, and patients whose ampulla had a type I surface structure had only inflammatory or hyperplastic changes. In addition, abnormal vessels were seen only in adenocarcinomas and never in adenomas., Conclusions: MENBI has the ability and potential to predict histological characteristics of ampullary lesions.