Dissection and removal of bile duct plastic stents penetrating the duodenal papilla: report of three rare cases.

We encountered three cases with incidental penetration of a straight Amsterdam-type bile duct plastic stent into the duodenal papilla. All patients had undergone insertion of a biliary plastic stent due to common bile duct stones. However, in all three cases, we observed penetration of the biliary plastic stent into the duodenal papilla just before the elective surgery or at the time of plastic stent replacement. We, therefore, performed stent dissection using a bipolar snare and were able to safely remove the plastic stents in all three cases. We believe that this is the first report of plastic stent dissection using a bipolar snare.

MAFK Polymorphisms Located in 3'-UTR are Associated with Severity of Atrophy and CDKN2A Methylation Status in the Gastric Mucosa.

Objective: This study aimed to clarify the association of MAFK polymorphisms (rs4268033, rs3735656, and rs10226620) with the degree of gastric mucosal atrophy and CDKN2A CpG methylation status. Methods: A total of 491 subjects were enrolled in this study. Genotypes and methylation status were determined by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and methylation-specific PCR (Fujita Health University, HM18-094). Methods: A total of 491 subjects were enrolled in this study. Genotypes and methylation status were determined by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and methylation-specific PCR (Fujita Health University, HM18-094). Results: Either rs3735656 or rs10226620, located in the 3'-UTR of MAFK, was significantly associated with the severity of gastric mucosal atrophy using a dominant genetic model (odds ratio [OR], 2.10; p = 0.0012, and OR, 1.98; p = 0.0027, respectively). However, using a recessive genetic model, no significant association was found between three polymorphisms and gastric mucosal atrophy. The serum pepsinogen I/II ratio was significantly lower in subjects with minor alleles of rs3735656 and rs10226620 than in subjects with the wild homozygous allele (p = 0.018 and 0.013, respectively). In a subgroup including 400 of the 491 subjects, the CpG of p14ARF and p16 INK4a were methylated in 132 and 112 subjects, respectively. Fifty subjects had both CpG methylations and 206 subjects had neither methylation. When comparing the groups with both and neither methylations, there were no significant associations between three polymorphisms and CDKN2A methylation using a dominant genetic model. However, all polymorphisms investigated in this study (rs4268033, rs3735656, and rs10226620) were significantly associated with CDKN2A methylation in a recessive genetic model (OR, 3.58; p = 0.0071, OR, 4.49; p = 0.0004, and OR, 3.45; p = 0.0027, respectively). Conclusions: Our results indicate that carrying the minor allele of the MAFK polymorphisms, particularly when they are located in the 3'-UTR, has a high risk for the severity of gastric mucosal atrophy; furthermore, CDKN2A CpG methylation may develop in subjects with homozygous minor allele of these polymorphisms.

Effect of DNMT3A polymorphisms on CpG island hypermethylation in gastric mucosa.

BACKGROUND: CpG methylation of tumor suppressor genes occurs in the early stage of carcinogenesis. Detecting risk factors for aberrant CpG methylation is clinically important for predicting cancer development. DNA methyltransferase (DNMT) 3a is considered to play critical roles in the DNA methylation process during pathogenesis. In this study, we evaluated the association between DNMT3A polymorphisms (rs6733868 and rs13428812) and CpG methylation status in non-cancerous gastric mucosa. METHODS: We determined the DNMT3A genotype and CpG methylation status of 4 genes (p14ARF, p16INK4a, DAPK, and CDH1) in 510 subjects without gastric cancer. Helicobacter pylori (HP) infection status was determined by the rapid urease test, urea breath test, speculum examination, or serum antibody test. We determined the DNMT3A genotype using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). CpG methylation status was determined by methylation-specific polymerase chain reaction (MSP). When the methylated band was stronger than 10 ng/µL according to the DNA marker, we judged CpG island hypermethylation (CIHM) to be present. Associations between genotypes and susceptibilities were assessed by logistic regression analysis. RESULTS: The minor allele frequencies of both polymorphisms (rs6733868 and rs13428812) were lower in the CpG methylated groups of each of the 4 genes (p14ARF, p16INK4a, DAPK, and CDH1). Using a dominant genetic model, rs6733868 was significantly associated with the hypermethylation of each gene, whereas rs13428812 was associated with the methylation of 3 genes (all except p14ARF). When low-CIHM was defined as 1 or 2 CpG islands methylated and high-CIHM was defined as 3 or more CpG islands methylated, carrying the minor allele of rs6733868 was associated with both decreased low- and high-CIHM, and that of rs13428812 also was associated with a decrease. Comparing low-CIHM with high-CIHM, carrying the minor alleles of rs6733868 or rs13428812 was related to decreased susceptibility to high-CIHM. In HP-infected subjects, carrying the minor alleles of rs6733868 or rs13428812 had a significantly greater association with decreased susceptibility to high-CIHM. CONCLUSIONS: Our study indicates that polymorphisms of DNMT3A are associated with the accumulation of gene methylation in gastric mucosa. Carrying the minor alleles of rs6733868 or rs13428812 inhibits aberrant gene methylations, which are typically enhanced by HP infection.

Influence of MIF polymorphisms on CpG island hyper-methylation of CDKN2A in the patients with ulcerative colitis.

BACKGROUND: CDKN2A hypermethylation is among the major events associated with carcinogenesis and is also observed in non-neoplastic colonic mucosa in patients with ulcerative colitis (UC). Macrophage migration inhibitory factor (MIF) plays a crucial role in promoting gastrointestinal inflammation characteristic of UC. The aim of this study is to explore associations between CDKN2A methylation status and MIF polymorphisms (rs755622 and rs5844572). METHODS: One hundred and fifty-nine patients diagnosed with UC were enrolled in this study. The methylation status of p14ARF and p16INK4a was determined by MSP; MIF genotypes were identified by PCR-SSCP. RESULTS: We found no differences with respect to mean age, gender, clinical type (chronic continuous or relapse/remitting), or extent of disease among the patients with methylated and unmethylated p14ARF or p16INK4a. Carrying the rs755622 C allele indicated a significantly higher risk for p14ARF methylation (odds ratio (OR), 2.16; 95% confidence interval (CI), 1.08-4.32; p = 0.030); similarly, carrying the rs5844572 7-repeat allele indicated a significantly higher risk for p16INK4a methylation (OR, 2.57; 95% CI, 1.26-5.24; p = 0.0094) after an adjusted regression analysis. The carriers of the rs755662 C allele or the rs5844572 7-repeat allele were both at a significantly higher risk for methylation of both p14ARF and p16INK4a when compared to the cohort in which neither of the genes were methylated (OR, 2.70; 95% CI, 1.22-6.01; p = 0.015 and OR, 2.87; 95% CI, 1.25-6.62; p = 0.013, respectively). Additionally, carrying rs755622 C allele was significantly associated with CIHM in chronic continuous of clinical type and total colitis (OR, 25.9; 95% CI, 2.55-262.6; p = 0.0059 and OR, 4.38; 95% CI, 1.12-17.2; p = 0.034, respectively), and carrying 7-repeat allele of rs5844572 was significantly associated in chronic continuous type (OR, 14.5; 95%CI, 1.46-144.3; p = 0.022). CONCLUSIONS: Taken together, our findings suggest that MIF genotypes associated with inflammation may also be involved in promoting carcinogenesis via CDKN2A hypermethylation in patients diagnosed with UC.

Durvalumab-induced Immune-related Hepatitis in a Patient with Non-small Cell Lung Cancer.

We herein report the case of a 79-year-old patient with unresectable stage III non-small cell lung cancer who developed immune-related hepatitis caused by durvalumab administration. Durvalumab was administered at 10 mg/kg every two weeks after the treatment with carboplatin (AUC2), paclitaxel (35 mg/m2), and 60 Gy radiation. At the day 208 in which the 14th durvalumab administration was scheduled, the patient was urgently hospitalized due to CTCAE Grade 4 hepatic dysfunction detected during the an outpatient blood sampling test. He was diagnosed with immune-related hepatitis and started on methylprednisolone 60 mg/day. After 51 days, his liver dysfunction improved and he was discharged.

Differential prognostic impact between completion and non-completion of a 5-month cardiac rehabilitation program in outpatients with cardiovascular diseases.

BACKGROUND: Cardiac rehabilitation (CR) is an essential component of care for patients with cardiovascular diseases (CVD). We aimed to evaluate clinical outcomes in outpatients with CVD who did and did not complete a 5-month CR program. METHODS: Three hundred thirty-two outpatients with CVD who participated in a 5-month CR program and were followed-up for maximum 5 years were registered. We divided the patients into two groups: those who completed the CR program (success group, n = 175) and those who could not (non-success group, n = 157). Both long-term (5 years) and short-term (5 months) clinical outcomes were compared between the two groups. RESULTS: There were no significant differences in patient characteristics at baseline between the success and non-success groups. With regard to both long-term and short-term clinical outcomes, the rates of all-cause death and hospital admission in the success group were significantly lower than those in the non-success group by a Kaplan-Meier analysis. There was a significant difference in short-term CVD death and hospital admission between the groups, but not for long-term CVD death and hospital. In long-term period, all-cause death and hospital admission was independently associated with completion of the CR program in addition to the presence of peripheral artery disease and VE vs. VCO2 slope after adjusting for age, gender, body mass index, types of CVD and medications. CONCLUSIONS: Completion of a 5-month CR program was associated with the prevention of all-cause death and hospital admission, but not CVD death and hospital admission in the long-term, which suggests that we need to reconsider this issue.

Possibility of Cardio-renal Protection by Long-term Cardiac Rehabilitation in Elderly Patients with Cardiovascular Diseases.

Objective Cardiac rehabilitation (CR) improves the mortality in patients with cardiovascular disease (CVD). Even in elderly patients with CVD, CR may improve the activities of daily living (ADL). Methods Eighty-eight outpatients over 65 years of age at the beginning of a CR program (baseline) at Fukuoka University Hospital who had CVD and could be followed-up for up to 5 years were enrolled. CVD included ischemic heart disease, postoperative valvular heart disease, dissecting aneurysm of the aorta and peripheral artery disease. The patients were divided into 2 groups according to the average estimated glomerular filtration rate (eGFR) at baseline (55.4±14.8 mL/min/1.73 m2): high (≥55.4, n=44) and low (<55.4, n=44)-eGFR groups. The anaerobic threshold (AT) during exercise and left ventricular ejection fraction (LVEF) were measured by cardiopulmonary exercise (CPX) and ultrasound cardiography, respectively. The serum brain natriuretic protein (BNP) was also measured every year. Results The average age at baseline in all patients was 73±6 years. In all patients, the level of eGFR did not significantly change for 5 years (55±15 mL/min/1.73 m2 at baseline vs. 48±14 at the end of the study). The AT (3.7±1.0 METs at baseline vs. 3.3±0.5), LVEF (57±13% vs. 64±10%) and BNP (260±452 pg/mL vs. 308±345) were also maintained for 5 years. In both the low- and high-eGFR groups, the eGFR, AT during exercise, LVEF and BNP at the end of the study were not significantly changed compared to the baseline values, although some changes were observed during the follow-up period. Conclusion Long-term CR in CVD outpatients over 65 years of age helped maintain the AT, LVEF, BNP and eGFR for 5 years. CR afforded cardio-renal protection in elderly patients with CVD.

Cardiac rehabilitation in patients with cardiovascular disease leads various hemodynamic parameters obtained using simple non-invasive tests to their appropriate levels.

We evaluated whether comprehensive cardiac rehabilitation (CR) in patients with cardiovascular disease (CVD) could improve various hemodynamic parameters obtained using simple non-invasive tests. We analyzed 48 CVD patients with (n = 38, CR group) or without (n = 10, non-CR group) a CR program, and prospectively followed them for 12 months. Various parameters were measured at baseline and after 12 months using 3 simple non-invasive tests: blood pressure (BP) and severity of atherosclerosis [arterial velocity pulse index (AVI) and atrial pressure volume index] were determined using PASESA®, an index of total autonomic nerve activity and a coefficient of variation of the R-R interval (CVRR) were determined using eHEART®, and the total peripheral resistance, stroke volume and cardiac index (CI) were determined using nico®. The main hemodynamic parameters did not change between baseline and 12 months in both groups. Patients in the CR group were divided into higher (H-) and lower (L-) systolic BP (SBP) or AVI according to the average value of SBP or AVI at baseline in the CR group. Patients with H-SBP or H-AVI in the CR group showed a significant reduction of SBP or AVI at 12 months. In addition, patients in the CR group were divided into H- and L- CI or CVRR according to the average value of CI or CVRR at baseline in the CR group. Patients with L-CI or L-CVRR in the CR group significantly improved after 12 months. In conclusion, CR may lead various hemodynamic parameters obtained using simple non-invasive tests to their appropriate levels.

Assessment of various parameters using simple non-invasive tests in patients with cardiovascular diseases with or without cardiac rehabilitation.

Cardiac rehabilitation (CR) improves cardiac function and exercise capacity in patients with cardiovascular disease (CVD). Simpler techniques are needed for use by physicians in the examination room to assess the usefulness of CR. We enrolled 46 consecutive CVD patients in a CR program (CR group) and prospectively followed them for 3 months. We compared them to 18 age-, gender- and body mass index-matched CVD patients without CR (non-CR group). Various parameters were measured at baseline and after 3 months using 3 simple non-invasive tests: severity of atherosclerosis [arterial velocity pulse index and arterial pressure volume index (API)] were determined using PASESA®, an autonomic nerve total activity amount index and a coefficient of variation of the R-R interval (CVRR) were determined using eHEART®, and peripheral resistance index, pressure rate product, stroke volume and cardiac index were determined using nico®]. There were no significant differences in patient characteristics including percentages (%) of ischemic heart disease and heart failure between the non-CR and CR groups. Systolic blood pressure (SBP), diastolic BP, heart rate and API at baseline significantly decreased and CVRR at baseline significantly increased after 3 months in the CR group, but not in the non-CR group. In addition, ΔAPI (Δ = the value after 3 months minus the value at baseline) was positively associated with ΔSBP in the CR group. In conclusion, CR significantly decreased BP and improved atherosclerosis and sympathetic nerve activity. These findings suggest that simple non-invasive tests may be useful for assessing the effects of CR.

Influence of a Cardiac Rehabilitation Program on Renal Function in Patients With Cardiovascular Disease in a One-Year Follow-Up.

BACKGROUND: Exercise training may improve renal function in patients with chronic kidney disease (CKD). The effect of cardiac rehabilitation (CR) with exercise training on renal function has not yet been established. We evaluated the effects of CR on renal function in patients with cardiovascular disease (CVD). METHODS: Twenty-three CVD patients in a 1-year CR program (CR group) who had ischemic heart disease (IHD) and/or heart failure were compared with 26 age- and gender-matched CVD patients without CR (non-CR group, standard pharmacological care alone). At baseline and after 1 year, urea nitrogen (UN), creatinine (Cr), potassium (K), estimated glomerular filtration rate (eGFR) and hematocrit (Hct) in blood were assessed. RESULTS: There were no differences in the patient characteristics at baseline between the CR and non-CR groups except for the percentages of heart failure and the use of calcium channel blocker. After 1 year, there were no significant changes in UN, Cr, K, eGFR or Hct in either the CR or non-CR groups. The patients in the CR group were divided into two groups according to the eGFR level at baseline: low (n = 12, eGFR < 51 mL/minute/1.73 m2, indicating mild-to-moderate CKD) and high (n = 11, eGFR ≥ 51 mL/minute/1.73 m2) eGFR groups. Although there were no differences in the patient characteristics at baseline between the low and high eGFR groups, the low eGFR group showed a significant increase in eGFR after the 1-year CR program. CONCLUSIONS: CR may improve renal function in patients with mild-to-moderate CKD.