Risk factors for postoperative bleeding and early death in percutaneous endoscopic gastrostomy: A multicenter retrospective study.

BACKGROUND AND AIM: Comprehensive reports on the risk factors for bleeding and early death after percutaneous endoscopic gastrostomy (PEG) are limited. In this multicenter study, we retrospectively investigated the risk factors for bleeding and early death after PEG. METHODS: Patients (n = 1234) who underwent PEG between 2015 and 2020 at Osaka Medical and Pharmaceutical University and its affiliated hospitals (11 institutions in total) were evaluated for postoperative bleeding and early death (within 60 days) after PEG according to patient characteristics, construction method, medical history, medications, preoperative hematological findings, and perioperative adverse events. Multivariate logistic regression was performed to identify independent predictors of bleeding and early death after PEG. RESULTS: The risk factors for bleeding after PEG were PEG tube insertion using the modified introducer method (odds ratio [OR], 4.37; P = 0.0003), low platelet count (OR, 0.99; P = 0.014), antiplatelet therapy (OR, 2.11; P = 0.036), and heparinization (OR, 4.50; P = 0.007). Risk factors for early death were low body mass index (BMI) (OR, 0.89; P = 0.015), low serum albumin levels (OR, 0.50; P = 0.035), and comorbidity of active cancer (OR, 4.03; P < 0.0001). There was no significant association between bleeding and early death after PEG. CONCLUSIONS: We identified several risk factors for bleeding and early death after PEG. Risk factors for bleeding were PEG tube insertion using the modified introducer method, low platelet count, antiplatelet therapy, and heparinization. Risk factors for early death were low BMI, low serum albumin levels, and comorbidity of active cancer.

Prospective clinical study of endoscopic ultrasound-guided biliary drainage using novel balloon catheter (with video).

BACKGROUND AND AIM: On endoscopic ultrasound (EUS)-guided biliary drainage, fistula dilation may be accompanied by leakage of bile juice, potentially along with bacteria or air, so this procedure should be kept as simple and short as possible. To date, various techniques to dilate the fistula have been reported. This prospective, single-center, single-arm study evaluated the technical feasibility and safety of EUS-guided biliary drainage using novel balloon catheters. METHODS: Tip of novel balloon catheters is only 3 Fr and tapered, and the catheters also show favorable push ability. First, biliary tract was punctured using 19-G fine needle aspiration needle. Next, we immediately inserted the novel balloon catheter, and the biliary tract and intestinal wall were dilated. Then, we performed metallic stent placement without any dilation fistula. RESULTS: A total of 20 patients were prospectively enrolled in this study. Technical success rate was 100%. Eleven patients underwent EUS-guided choledochoduodenostomy, and nine patients underwent EUS-guided hepaticogastrostomy. Median procedure time was only 11 min (range, 8-16 min) for EUS-guided choledochoduodenostomy and 14 min (range, 11-18 min) for EUS-guided hepaticogastrostomy. Adverse events were seen in 15% (3/20; self-limited abdominal pain n = 2, peritonitis n = 1). CONCLUSIONS: Although additional cases and a randomized controlled comparison with another dilation technique such as the graded dilation or cystotome dilation technique are needed, our technique may be helpful for EUS-guided biliary drainage.

Clinical utility of endoscopic ultrasound-guided biliary drainage as a rescue of re-intervention procedure for high-grade hilar stricture.

BACKGROUND AND AIM: Re-intervention after stent placement for malignant hepatic hilum obstruction (HBO) is challenging. endoscopic ultrasound-guided biliary drainage (EUS-BD) has been developed as an alternative method for failed endoscopic retrograde cholangiopancreatography (ERCP). In this retrospective study, the clinical utility of EUS-BD as a rescue drainage technique for HBO patients who failed re-intervention under ERCP guidance was evaluated. METHODS: Between April 2012 and August 2015, patients with HBO were enrolled. Patients' characteristics, kinds of metallic stents, configuration of stent placement, overall survival, stent patency, and results of re-intervention were reviewed, along with the re-intervention technical success rate. RESULTS: The biliary stricture type was Bismuth type IV in 59% (23/39) and types IIIa and b in 20.5% (8/39) each. Biliary metallic stent placement was bilateral in 38.5% (15/39), and unilateral in 61.5% (24/39). Primary stent dysfunction was observed in 71.8% (28/39) of cases. Planned re-intervention under ERCP guidance was attempted in 26 patients. The technical success rate was 62% (16/26). For the 10 patients who failed re-intervention under ERCP guidance, EUS-BD was planned. The technical success rate was 100% (10/10). The procedure time was 25.8 min. Adverse events were not seen in any patients. Stent patency after re-intervention was not significantly different between ERCP (165 days) guidance and EUS-BD (152 days) guidance (P = 0.463) CONCLUSIONS: In conclusion, EUS-BD as a re-intervention method for metallic stent obstruction was safe and feasible. If ERCP was failed, EUS-BD may be one of option as re-intervention method for high-grade hilar stricture.

Evaluation of the safety of endoscopic radiofrequency ablation for malignant biliary stricture using a digital peroral cholangioscope (with videos).

BACKGROUND AND AIM: The clinical impact of catheter-based radiofrequency ablation (RFA) under endoscopic retrograde cholangiopancreatography (ERCP) guidance has recently been reported; however, severe adverse events have also been noted. If tumor is not present in the biliary tract, severe adverse events such as perforation or bleeding as a result of vessel injury around the biliary tract may occur. In addition, the effectiveness of RFA may not be sufficient based solely on radiographic guidance. The aim of the present study was to evaluate the actual feasibility of intraductal RFA by peroral cholangioscope (POCS) evaluation before/after RFA. METHODS: In this retrospective study carried out between July and September 2016, consecutive patients who underwent RFA for malignant biliary stricture and POCS evaluation before/after RFA were enrolled. Primary endpoint of this study was technical feasibility of RFA, which was evaluated by POCS. Secondary endpoints were rates and types of adverse event. RESULTS: A total of 12 consecutive patients were retrospectively enrolled in this study. Stent placement using uncovered metal stents had been previously done in six patients before RFA. Tumor was seen in the biliary tract in all patients. RFA was technically successful in all patients, and clinical success was confirmed in all patients by POCS imaging. Adverse events were seen in only one patient. Median stent patency was 154 days. CONCLUSIONS: RFA for malignant biliary stricture may be safe. To confirm the feasibility and efficacy of RFA, additional cases, prospective studies, and a comparison study between with and without endobiliary RFA are needed.

Prospective evaluation of digital single-operator cholangioscope for diagnostic and therapeutic procedures (with videos).

BACKGROUND AND AIM: Recently, the digital single-operator cholangioscope (SPY-DS) has become available. This system may allow diagnosis by direct visualization and allow performance of various therapeutic procedures. The aim of the present study was to prospectively evaluate the clinical utility of DSOCS for diagnostic and therapeutic procedures for biliary disease. METHODS: Technical success was defined as successful visualization of target lesions in the biliary tract and carrying out forceps biopsy as a diagnostic procedure, and successfully carrying out treatment such as guidewire insertion for the area of interest, electrohydraulic lithotripsy (EHL), or migrated stent removal. Also, the present study aimed at investigating diagnostic yield of the cholangioscopic findings and biopsy specimens. RESULTS: A total of 55 consecutive patients were prospectively enrolled in this study; a diagnostic procedure was done in 33 patients, and a therapeutic procedure was done in 22 patients. Overall accuracy of visual findings was 93%, with a sensitivity of 83%, a specificity of 89%, positive predictive value (PPV) of 83%, and negative predictive value (NPV) of 100%. However, the overall accuracy of forceps biopsy was 89%, with a sensitivity, specificity, and PPV of 100%, and NPV of 90%. Overall technical success rate of therapeutic procedures such as selective guidewire insertion, EHL or migrated stent removal was 91% (20/22). Finally, adverse events were seen in two cases in the diagnostic group, but were not seen in the therapeutic group. CONCLUSION: Although additional cases and a randomized, controlled study with another cholangioscope are needed, diagnostic and therapeutic procedures using SPY-DS appear to be feasible and safe.

Comparison of the clinical impact of endoscopic ultrasound-guided choledochoduodenostomy and hepaticogastrostomy for bile duct obstruction with duodenal obstruction.

BACKGROUND AND STUDY AIM: To date, only a few reports with small numbers of patients have described double stenting (biliary and duodenal), in particular endoscopic ultrasound (EUS)-guided biliary drainage, for patients with obstructive jaundice. In addition, no reports have sought to determine which EUS-guided biliary drainage route has better outcomes. The aim of the current study was to investigate adverse events and stent patency in patients who underwent EUS-guided biliary drainage and duodenal stenting. PATIENTS AND METHODS: Patients who were admitted to the Osaka Medical College with obstructive jaundice caused by lower biliary obstruction and duodenal obstruction due to malignant tumor between June 2012 and April 2014 were retrospectively enrolled in the study. RESULTS: A total of 39 patients were enrolled in the study; 13 underwent EUS-guided choledochoduodenostomy (EUS-CDS), and 26 underwent EUS-guided hepaticogastrostomy (EUS-HGS). Adjusted analyses for covariates using propensity scores showed that the EUS-HGS group had significantly longer stent patency than the EUS-CDS group (duodenal stent patency: median 113 vs. 34 days; hazard ratio [HR] 0.415, 95 % confidence interval [CI] 0.175 - 0.984; P = 0.046; biliary stent patency: median 133 vs. 37 days; HR 0.391, 95 %CI 0.156 - 0.981; P = 0.045). On logistic regression analysis, only EUS-CDS was associated with adverse events, in particular reflux cholangitis (OR 10.285, 95 %CI 1.686 - 62.733; P = 0.012). CONCLUSION: In cases of obstructive jaundice with duodenal obstruction, EUS-HGS may be better than EUS-CDS, with longer stent patency and fewer adverse events.

Yield of endoscopic ultrasound-guided fine needle aspiration and endoscopic retrograde cholangiopancreatography for solid pancreatic neoplasms.

OBJECTIVE: Both endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and endoscopic retrograde cholangiopancreatography (ERCP) cytology may provide tissue diagnoses in solid pancreatic neoplasms. However, there are scant data comparing these two methods. This study aims at retrospectively comparing EUS-FNA and ERCP tissue sampling and ability of cytopathological diagnosis in solid pancreatic neoplasms and to determine usefulness and adverse events of combining both procedures. MATERIAL AND METHODS: Two hundred and thirty four patients suspected to have solid pancreatic mass on abdominal ultrasound and/or computed tomography (CT) were enrolled. EUS-FNA (group A), ERCP cytology (group B) and combined procedures (Group C) performed in 105, 91 and 38 cases, respectively. RESULTS: Sensitivity, specificity and accuracy were 98.9%, 93.3% and 98.1% for group A, and 72.1%, 60% and 71.4% for group B. Those for group C were all 100%. Sensitivity for malignancy in the pancreas head was 100% for group A and 82.4% for group B, and in the pancreas body and tail, 97.6% for group A and 57.1% for group B. EUS-FNA was more sensitive than ERCP cytology in diagnosing malignant pancreatic neoplasms 21-30 mm in size (p = 0.0068), 31-40 mm (p = 0.028) and ≥ 41 mm (p < 0.0001). Sensitivity for pancreatic malignancy with group C was 100% regardless of mass location or size. Adverse events were 1.9%, 6.6% and 2.6% following EUS-FNA, ERCP and combined procedures, respectively. CONCLUSIONS: EUS-FNA is superior to ERCP cytology for diagnosis of solid pancreatic neoplasms. Although combination of both procedures provide efficient tissue diagnosis and with a minimal adverse events rate, a prospective study including larger number of patients is required.

Clinical Outcome of Endoscopic Ultrasound-Guided Liver Abscess Drainage Using Self-Expandable Covered Metallic Stent (with Video).

BACKGROUND: Percutaneous drainage (PCD) is now the first-line drainage method for liver abscess because of its minimal invasiveness and high technical success rate. However, this procedure has several disadvantages, such as extra-drainage and self-tube removal. Recently, EUS-guided liver abscess drainage (EUS-AD) has been developed. However, only a few reports of EUS-AD have been reported. In addition, the clinical benefits of PCD and EUS-AD have not been reported. AIMS: In the present study, the safety and feasibility of EUS-AD using fully covered SEMS (FCSEMS) and the clinical outcomes of EUS-AD and PCD were examined retrospectively. METHODS: Twenty-seven consecutive patients who underwent PCD or EUS-AD between April 2012 and April 2015 were included in this study. EUS-AD was performed using FCSEMS. In addition, to prevent stent migration, 7-Fr pig tail plastic stent was placed within FCSEMS. RESULTS: Technical success was achieved in all patients of both groups. Clinical success was 100 % in the EUS-AD group although it was 89 % in PCD group (P = 034). Three adverse events were seen in the PCD group (self-tube removal n = 1, tube migration n = 2), but no adverse events were seen in the EUS-AD group. The median hospital stay was significantly shorter in the EUS-AD group than in the PCD group (21 vs 41 days, P = 0.03). CONCLUSION: Because of the short hospital stay, the high clinical success rate, and the low adverse event rate compared to PCD, EUS-AD has potential as a first-line treatment for liver abscess.

Endoscopic ultrasound-guided biliary drainage for right hepatic bile duct obstruction: novel technical tips.

Endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD) is not normally indicated for an obstructed right intrahepatic bile duct (IHBD). The technical feasibility and clinical efficacy of a novel technique of EUS-BD for right IHBD obstruction were evaluated. A total of 11 patients underwent drainage using either a left or a right biliary access route. The causes of obstructive jaundice were cholangiocarcinoma (n = 6), pancreatic cancer (n = 3), gastric cancer (n = 1), and colon cancer (n = 1). After placement of an uncovered metal stent to bridge the obstruction, a hepaticogastrostomy was completed using a covered stent. Mean procedure time was 33.9 ±â€Š10.0 minutes. Technical and functional success were achieved in all patients, and no adverse events occurred. This novel method appears to be safe and effective for right IHBD obstruction.

Paraoxonase-1 suppresses experimental colitis via the inhibition of IFN-γ production from CD4 T cells.

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, where excessive Th1 cell responses are observed. We performed experiments to identify immunologically bioactive proteins in human plasma and found that paraoxonase (PON)-1, which has esterase activity and is associated with high-density lipoproteins, inhibited the IFN-γ production by both murine and human differentiating Th1 cells. Trinitrobenzene sulfonic acid-induced colitis was attenuated by the administration of PON-1. The beneficial effects of PON-1 were associated with a reduced ratio of IFN-γ-producing CD4 T cells in the mesenteric lymph nodes and decreased production of T cell-related cytokines in the colon. PON-1 inhibited the TCR-induced activation of ERK-MAPK signaling and the nuclear translocation of NF-κB in CD4 T cells. Interestingly, an excessive CD4 T cell response was observed in PON-1-deficient mice under physiological and pathological conditions. Additionally, the efficacy of PON-1 or G3C9-C284A (G3C9), which shows a higher esterase activity than PON-1, on colitis was similar to that of an anti-TNF-α mAb, which is a clinically used CD treatment. Moreover, G3C9 more effectively suppressed CD4(+)CD45RB(high) cell transfer-induced chronic colitis in mice than did PON-1, and the efficacy of G3C9 against the colitis was similar to that of the anti-TNF-α mAb. Therefore, PON-1 (or G3C9) administration may be clinically beneficial for CD patients.

Stent length is impact factor associated with stent patency in endoscopic ultrasound-guided hepaticogastrostomy.

BACKGROUND AND STUDY AIM: Despite high technical and functional success rates with endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS), rates of adverse events have also been high. No reports have focused on EUS-HGS alone with a large sample size about predictors of stent patency. The present study examined predictors of stent patency in patients who underwent EUS-HGS. PATIENTS AND METHODS: The consecutive 51 patients who underwent EUS-HGS using one metallic stent were retrospectively enrolled in this study. Baseline characteristics, stent length from the hepatic portion and in the luminal portion, kinds of stent dysfunction, and stent patency were reviewed. RESULTS: Median duration of stent patency was significantly shorter with stent length in the luminal portion <3 cm (52 days) than with ≥3 cm (195 days; P < 0.01). On the other hand, median duration of stent patency did not differ significantly between ≥4 cm (194 days) and <4 cm (127 days; P = 0.1726). Length of stent in the luminal portion ≥3 cm (Hazard ration [HR], 9.242; 95% confidence interval [CI], 3.255-26.244, P < 0.05) and performance of chemotherapy (HR, 3.022; 95% CI, 1.448-6.304, P < 0.05) were also associated with long stent patency on the Cox proportional hazards model. CONCLUSION: In conclusion, to obtain long-term stent patency, our data suggest that a stent length ≥3 cm in the luminal portion may be suitable for EUS-HGS.

MnSOD downregulation induced by extremely low 0.1 mGy single and fractionated X-rays and microgravity treatment in human neuroblastoma cell line, NB-1.

A human neuroblastoma cell line, NB-1, was treated with 24 h of microgravity simulation by clinostat, or irradiated with extremely small X-ray doses of 0.1 or 1.0 mGy using single and 10 times fractionation regimes with 1 and 2 h time-intervals. A quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) examination was performed for apoptosis related factors (BAX, CYTC, APAF1, VDAC1-3, CASP3, CASP8, CASP9 P53, AIF, ANT1 and 2, BCL2, MnSOD, autophagy related BECN and necrosis related CYP-40. The qRT-PCR results revealed that microgravity did not result in significant changes except for a upregulation of proapoptotic VDAC2, and downregulations of proapoptotic CASP9 and antiapoptotic MnSOD. After 0.1 mGy fractionation irradiation, there was increased expression of proapoptotic APAF1 and downregulation of proapoptotic CYTC, VDAC2, VDAC3, CASP8, AIF, ANT1, and ANT2, as well as an increase in expression of antiapoptotic BCL2. There was also a decrease in MnSOD expression with 0.1 mGy fractionation irradiation. These results suggest that microgravity and low-dose radiation may decrease apoptosis but may potentially increase oxidative stress.

Combined treatment with dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin and elemental diets reduced indomethacin-induced intestinal injury in rats via the increase of mucosal glucagon-like peptide-2 concentration.

The gut incretin glucagon-like peptide-1 (GLP-1) and the intestinotropic hormone GLP-2 are released from enteroendocrine L cells in response to ingested nutrients. Treatment with an exogenous GLP-2 analogue increases intestinal villous mass and prevents intestinal injury. Since GLP-2 is rapidly degraded by dipeptidyl peptidase 4 (DPP4), DPP4 inhibition may be an effective treatment for intestinal ulcers. We measured mRNA expression and DPP enzymatic activity in intestinal segments. Mucosal DPP activity and GLP concentrations were measured after administration of the DPP4 inhibitor sitagliptin (STG). Small intestinal ulcers were induced by indomethacin (IM) injection. STG was given before IM treatment, or orally administered after IM treatment with or without an elemental diet (ED). DPP4 mRNA expression and enzymatic activity were high in the jejunum and ileum. STG dose-dependently suppressed ileal mucosal enzyme activity. Treatment with STG prior to IM reduced small intestinal ulcer scores. Combined treatment with STG and ED accelerated intestinal ulcer healing, accompanied by increased mucosal GLP-2 concentrations. The reduction of ulcers by ED and STG was reversed by co-administration of the GLP-2 receptor antagonist. DPP4 inhibition combined with luminal nutrients, which up-regulate mucosal concentrations of GLP-2, may be an effective therapy for the treatment of small intestinal ulcers.

EUS-guided hepaticogastrostomy combined with fine-gauge antegrade stenting: a pilot study.

BACKGROUND AND STUDY AIM: To minimize bile leakage and avoid possible death because of stent migration in endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS), we have recently combined EUS-HGS with EUS-guided antegrade stenting (EUS-AS) of the biliary obstruction using a novel uncovered metallic stent with a fine-gauge delivery system. In this pilot study, we evaluated the feasibility and adverse events associated with this combination therapy using the novel stent. PATIENTS AND METHODS: We performed EUS-guided antegrade stenting and hepaticogastrostomy in 12 consecutive patients. RESULTS: The novel EUS-AS stent was placed across the ampulla of Vater in 8 patients and above the ampulla in 4. Technical and functional success rates were 100 %. In addition, the insertion of the first stent was achieved in all patients without dilation of the fistula between stomach and intrahepatic bile duct. Although 1 patient experienced mild pancreatitis, adverse events such as bile peritonitis or stent dysfunction did not occur during follow-up (mean 122 days, range 62 - 210 days). CONCLUSION: This method appears to safely and effectively avoid adverse events associated with EUS-HGS.

Novel method of endoscopic ultrasound-guided hepaticogastrostomy to prevent stent dysfunction.

BACKGROUND AND STUDY AIM: The present study assesses the feasibility as well as the technical and functional success rates of a novel endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) technique called the locking stent method that uses end-bare covered metallic stents (EBCMS). METHODS: Twenty consecutive patients who were histologically diagnosed with unresectable cancer complicated with obstructive jaundice underwent EUS-HGS due to failed endoscopic biliary drainage or inaccessible papilla. We retrospectively collected clinical data for these patients including technical and functional success rates and complications. RESULTS: Seven were treated by EUS-HGS (EUS-HGS group), and 13 were treated using the locking stent EUS-HGS method (LS group). Technical and functional success rates were 100% in both groups. Procedural duration did not significantly differ between the EUS-HGS and LS groups (26.9 ± 9.0 versus 32.3 ± 11.1 min, P = 0.30). Two patients developed complications related to stent migration in the EUS-HGS group. In contrast, although mild post-procedural bile peritonitis required conservative treatment for a few days, none of the stents malfunctioned in the LS group. CONCLUSION: Our method can safely and effectively prevent stent dysfunction, but validation in a prospective clinical trial is required.

Can endoscopic ultrasound-guided fine needle aspiration offer clinical benefit for thick-walled gallbladders?

BACKGROUND: No previous studies have compared cytology obtained under endoscopic transpapillary gallbladder drainage (ETGD) and EUS-guided fine needle aspiration (EUS-FNA) for thick-walled gallbladders. AIM: The present study investigated the diagnostic yield of bile cytology under ETGD and EUS-FNA for gallbladder tumors. METHODS: A total of 69 patients were diagnosed as having gallbladder wall thickening. Among these patients, 28 patients were diagnosed by clinical follow-up, solely by imaging such as computed tomography or by histological examination of surgical specimens. The remaining 41 patients underwent ETGD and/or EUS-FNA. In these 41 patients, the clinical data collected included gender, age, diameter of gallbladder wall, site of gallbladder wall thickening, final diagnosis, adverse events, and diagnostic yield of ETGD and EUS-FNA. RESULTS: Cyto-histological diagnosis with EUS-FNA was higher than that with ETGD, with a sensitivity of 100 versus 71%, specificity of 100 versus 94%, and accuracy of 100 versus 88%, respectively, in the two groups. In addition, the sampling adequacy of EUS-FNA was 100%. Adverse events were seen in five patients in the ETGD group (mild pancreatitis), although no adverse events were seen in the EUS-FNA group (P = 0.08). CONCLUSION: Our results suggest that EUS-FNA can be safely performed for the diagnosis of gallbladder lesions. Further, this procedure may be the diagnostic method of choice over cytology of bile juice obtained via ETGD to obtain histological evidence of gallbladder cancer.

Mitochondria Play Essential Roles in Intracellular Protection against Oxidative Stress-Which Molecules among the ROS Generated in the Mitochondria Can Escape the Mitochondria and Contribute to Signal Activation in Cytosol?

Questions about which reactive oxygen species (ROS) or reactive nitrogen species (RNS) can escape from the mitochondria and activate signals must be addressed. In this study, two parameters, the calculated dipole moment (debye, D) and permeability coefficient (Pm) (cm s-1), are listed for hydrogen peroxide (H2O2), hydroxyl radical (•OH), superoxide (O2•-), hydroperoxyl radical (HO2•), nitric oxide (•NO), nitrogen dioxide (•NO2), peroxynitrite (ONOO-), and peroxynitrous acid (ONOOH) in comparison to those for water (H2O). O2•- is generated from the mitochondrial electron transport chain (ETC), and several other ROS and RNS can be generated subsequently. The candidates which pass through the mitochondrial membrane include ROS with a small number of dipoles, i.e., H2O2, HO2•, ONOOH, •OH, and •NO. The results show that the dipole moment of •NO2 is 0.35 D, indicating permeability; however, •NO2 can be eliminated quickly. The dipole moments of •OH (1.67 D) and ONOOH (1.77 D) indicate that they might be permeable. This study also suggests that the mitochondria play a central role in protecting against further oxidative stress in cells. The amounts, the long half-life, the diffusion distance, the Pm, the one-electron reduction potential, the pKa, and the rate constants for the reaction with ascorbate and glutathione are listed for various ROS/RNS, •OH, singlet oxygen (1O2), H2O2, O2•-, HO2•, •NO, •NO2, ONOO-, and ONOOH, and compared with those for H2O and oxygen (O2). Molecules with negative electrical charges cannot directly diffuse through the phospholipid bilayer of the mitochondrial membranes. Short-lived molecules, such as •OH, would be difficult to contribute to intracellular signaling. Finally, HO2• and ONOOH were selected as candidates for the ROS/RNS that pass through the mitochondrial membrane.

Potential predictors of disease progression for main-duct intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND AND AIM: The evidence for main pancreatic duct intraductal papillary mucinous neoplasms (MPD-IPMN) malignancy is based predominantly on investigation of resected cases, and the natural history is still unclear. The aim of the present study is to investigate the natural history of MPD-IPMN and examine potential predictors of disease progression in MPD-IPMN patients who conformed to "high-risk stigmata" criteria. METHODS: This study included consecutive 20 follow-up patients and 19 surgical patients with "high-risk stigmata" MPD-IPMN, in whom the diameter of the MPD was > 10 mm, branch duct was < 5 mm, and who underwent clinical follow up for ≥ 2 years. RESULTS: Among surgical patients, mural nodules and MPD diameter of invasive patients were significantly different compared with non-invasive patients. On the other hand, among follow-up patients, univariate analysis revealed the following potential predictors for disease progression: diameter of MPD ≥ 15 mm (hazard ratio [HR], 20.9; 95% confidence interval [CI], 2.59-173.4; P < 0.01); and diffuse lesions of MPD-IPMN (HR, 4.46; 95% CI, 1.10-18.0; P = 0.04). On the other hand, multivariate analysis identified only diameter of MPD ≥ 15 mm (HR, 19.2; 95% CI, 1.87-198.5; P = 0.01) as a potential predictor of disease progression. CONCLUSION: If MPD-IPMN patients have other severe complications or reasons for not undergoing surgical treatment, MPD diameter < 15 mm, negative cytology, and no mural nodules, conservative clinical follow up for several years may be an option.

[A case of xanthogranulomatous cholecystitis diagnosed by EUS-FNA in which changes were observed on FDG-PET].

An elderly man in his 70s presented with pain in the right hypochondrium. Computed tomography revealed thickening of the gall bladder wall and liver invasion. In addition, fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed an abnormal accumulation in the gall bladder, leading to a suspicion of gall bladder carcinoma. To confirm the diagnosis, endoscopic ultrasound-guided fine-needle aspiration was performed, which revealed a diagnosis of xanthogranulomatous cholecystitis (XGC). FDG-PET revealed decreased wall thickness and standardized uptake value a month later. Cholecystectomy was performed on the basis of a histological and clinical diagnosis of XGC. Histological examination revealed inflammatory and foamy cells and exuberant granulation of the gall bladder wall, confirming XGC.

Evidence of Nrf2/Keap1 Signaling Regulation by Mitochodria-Generated Reactive Oxygen Species in RGK1 Cells.

It has been known that reactive oxygen species (ROS) are generated from the mitochondrial electron transport chain (ETC). Majima et al. proved that mitochondrial ROS (mtROS) caused apoptosis for the first time in 1998 (Majima et al. J Biol Chem, 1998). It is speculated that mtROS can move out of the mitochondria and initiate cellular signals in the nucleus. This paper aims to prove this phenomenon by assessing the change in the amount of manganese superoxide dismutase (MnSOD) by MnSOD transfection. Two cell lines of the same genetic background, of which generation of mtROS are different, i.e., the mtROS are more produced in RGK1, than in that of RGM1, were compared to analyze the cellular signals. The results of immunocytochemistry staining showed increase of Nrf2, Keap1, HO-1 and 2, MnSOD, GCL, GST, NQO1, GATA1, GATA3, GATA4, and GATA5 in RGK1 compared to those in RGM1. Transfection of human MnSOD in RGK1 cells showed a decrease of those signal proteins, suggesting mtROS play a role in cellular signals in nucleus.