Impact of the COVID-19 pandemic on the treatment of acute cholangitis caused by choledocholithiasis: A single-center retrospective study in Japan.

Objectives: This study aimed to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on the treatment of acute cholangitis caused by choledocholithiasis. Methods: The Japanese government declared a state of emergency in April 2020 due to the COVID-19 pandemic. We retrospectively reviewed the medical records of 309 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis caused by choledocholithiasis between April 2017 and December 2022. Results: Patients were categorized into a pregroup (n = 134) and a postgroup (n = 175), depending on whether they were diagnosed before or after the state of emergency declaration. The total number of ERCP cases and the number of ERCP cases with endoscopic stone removals increased after the state of emergency declaration. Compared with the pregroup, the numbers of patients with performance status of 0-1 and surgically altered anatomy increased, whereas the numbers of patients taking oral antiplatelets or anticoagulants and those with cerebrovascular disease decreased in the postgroup. The number of single-stage endoscopic stone removals increased and hospital stays were significantly shorter in the postgroup. No differences in adverse event rates were detected between the two groups. Conclusions: Although our hospital provides tertiary care, the number of patients with cholangitis in good general condition and no underlying disease increased after the state of emergency declaration. The COVID-19 pandemic resulted in an increase in the number of single-stage endoscopic treatments and shortened hospital stays for patients with acute cholangitis caused by choledocholithiasis. No safety issues with ERCP were detected, even during the pandemic.

Unilateral drainage and chemotherapy prolong the patency of a plastic stent placed above the sphincter of Oddi in patients with malignant hilar biliary obstruction.

Objectives: To evaluate the results of inside stent therapy for unresectable malignant hilar biliary obstruction and identify factors related to stent patency duration. Methods: Of 44 patients who underwent initial inside-stent placement above the sphincter of Oddi from April 2017 to December 2022, 42 with the resolution of jaundice (clinical success rate, 95.5%) were retrospectively analyzed. Univariate and multivariate logistic regression analysis identified factors associated with stent patency duration. Results: Univariate analysis revealed significant differences in the drainage method (406 days for unilateral drainage vs. 305 days for bilateral drainage of the right and left liver lobes, p = 0.022) with or without chemotherapy (406 days with vs. 154 days without, p = 0.038). Multivariate analysis (Cox proportional hazards analysis) revealed similar results, with unilateral drainage (p = 0.031) and chemotherapy (p = 0.048) identified as independent factors associated with prolonged stent patency. Early adverse events were observed in two patients (4.8%; one cholangitis, one pancreatitis). Conclusions: Inside-stent therapy was safely performed in patients with malignant hilar biliary obstruction. Simple unilateral drainage and chemotherapy may prolong stent patency.

Evaluation of acute and midterm outcomes after complex combined antegrade/retrograde recanalization for occlusions of the femoropopliteal and infrapopliteal arteries.

INTRODUCTION: When antegrade recanalization of femoro- and/or infrapopliteal occlusions fails, retrograde access has become an established option. To evaluate the results of combined antegrade and retrograde recanalization of femoropopliteal and infrapopliteal occlusions, patients undergoing secondary retrograde recanalization attempts were analyzed retrospectively. METHODS: Primary endpoint was the success of the procedure (successful occlusion crossing using the ante-/retrograde technique). Secondary endpoints include complication rate, primary patency and target lesion revascularization (TLR) rate, amputation rate, changes in ankle-brachial index (ABI), and Rutherford-Becker class (RBC). Predictors for procedure failure and TLR were analyzed. RESULTS: We included 888 patients: 362 with femoropopliteal (group 1), 353 with infrapopliteal (group 2), and 173 with multi-level (group 3) recanalization. Critical limb threatening ischemia (CLTI) was present in group 1, 2, and 3 in 36%, 62%, and 76%, respectively. The intervention was successful in 92.5%, 93.8%, 90.8% of respective cases (p=0.455). The overall peri-interventional complication rate was 7.2%. At 6, 12 and 24 months, primary patency was highest in group 1 (63.9%, 45.8%, 33.3%), followed by group 3 (59.8%, 46.1%, 33.3%), and group 2 (58.5%, 43.1%, 30.4%), p=0.537). The risk of undergoing repeated TLR within 24 months was 31.4% for group 1, 39.1% for group 2, and 45.7% for group 3. At 24 months, the survival rate in groups 1, 2, 3 was 93.8%, 79.4% and 87.5%, respectively. During 24 months, 75 patients (8.4%) had to undergo amputation. Significant improvements in both ABI and RBC were present at discharge as well as at 6, 12 and 24 months (p<0.001). Dialysis dependency was a predictor of unsuccessful ante/retrograde recanalization (p=0.048). Lesion length (p=0.0043), dialysis (p=0.033) and recanalization level (p=0.013) increase the risk of TLR. CONCLUSION: Using a combined antegrade/retrograde access, recanalization of occluded femoropopliteal and/or infrapopliteal arteries can be achieved in a large number of cases. Due to the high rate of repeated TLR across all lesion localizations, the indication for ante- and retrograde recanalization may be limited to patients with CLTI.

A LASSO Cox Regression Predictive Model for Patients Undergoing Surgery for Pancreatic Body and Tail Adenocarcinoma Patients: Comparative Long-Term Survival Analysis of Radical Antegrade Modular Pancreatosplenectomy (RAMPS) and Standard Retrograde Pancreatosplenectomy (SPRS).

PURPOSE: This study was designed to assess the advantages of radical antegrade modular pancreatosplenectomy (RAMPS) over standard retrograde pancreatosplenectomy (SPRS) in terms of disease-free survival (DFS) by comparing clinical outcomes. METHODS: Clinical data from 154 patients who underwent distal pancreatectomy at Tianjin Medical University Cancer Institute and Hospital between January 2015 and August 2018 were collected. We compared the preoperative conditions, postoperative complications, and survival outcomes of patients who underwent two different surgical procedures. By creating a LASSO-Cox model, we determined the parameters affecting DFS and the risk ratios of the two surgical procedures on DFS. RESULTS: The R0 resection rate (85.23% vs. 68.18%, P = 0.003), negative posterior margin rate (96.59% vs. 75.76%, P < 0.001), and tumor bed recurrence rate (15.29% vs. 40.00%, P = 0.001) significantly differed between the RAMPS and SPRS groups. The 1-, 3-, and 5-year survival and DFS rates of the RAMPS group were significantly better than those of the SPRS group (P < 0.05). Disease-free survival analysis based on Kaplan-Meier curves revealed that RAMPS was superior to SPRS (P < 0.001). CONCLUSIONS: We recommend RAMPS as the preferred procedure for treating ductal adenocarcinoma of the pancreatic body and tail due to its enhanced lymph node repair capacity and visualization of posterior pancreatic sections, which can increase DFS in patients.

Post-cholecystectomy clip migration: an unusual nidus of choledocholithiasis: a case report.

Introduction and importance: Laparoscopic cholecystectomy is one of the common surgeries occurring worldwide and the gold standard for the management of gallstone disease. The non-absorbable surgical clips may slip and can migrate causing a variety of problems as such, choledocholithiasis. Case presentation: The authors report a case of 43-year-old female who presented with the complaint epigastric pain. She had undergone cholecystectomy 7 years back for symptomatic cholelithiasis. Ultrasonography of the abdomen showed a dilated common bile duct following which endoscopic retrograde cholangiopancreatography was done. A single black-colored stone with the metal clip was retrieved. Clinical discussion: Post-cholecystectomy clip migration should be considered as one of the differentials for choledocholithiasis. Ultrasonography of the abdomen shows the dilated common bile duct. Further management is done by endoscopic retrograde cholangiopancreatography. Conclusion: Surgical clips acting as nidus for choledocholithiasis is rare these days but should be considered as one of the differentials for pain abdomen.

Carbapenem-resistant Enterobacterales sepsis following endoscopic retrograde cholangiopancreatography: risk factors for 30-day all-cause mortality and the development of a nomogram based on a retrospective cohort.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has become a routine endoscopic procedure that is essential for diagnosing and managing various conditions, including gallstone extraction and the treatment of bile duct and pancreatic tumors. Despite its efficacy, post-ERCP infections - particularly those caused by carbapenem-resistant Enterobacterales (CRE) - present significant risks. These risks highlight the need for accurate predictive models to enhance postprocedural care, reduce the mortality risk associated with post-ERCP CRE sepsis, and improve patient outcomes in the context of increasing antibiotic resistance. OBJECTIVE: This study aimed to examine the risk factors for 30-day mortality in patients with CRE sepsis following ERCP and to develop a nomogram for accurately predicting 30-day mortality risk. METHODS: Data from 195 patients who experienced post-ERCP CRE sepsis between January 2010 and December 2022 were analyzed. Variable selection was optimized via the least absolute shrinkage and selection operator (LASSO) regression model. Multivariate logistic regression analysis was then employed to develop a predictive model, which was evaluated in terms of discrimination, calibration, and clinical utility. Internal validation was achieved through bootstrapping. RESULTS: The nomogram included the following predictors: age > 80 years (hazard ratio [HR] 2.61), intensive care unit (ICU) admission within 90 days prior to ERCP (HR 2.64), hypoproteinemia (HR 4.55), quick Pitt bacteremia score ≥ 2 (HR 2.61), post-ERCP pancreatitis (HR 2.52), inappropriate empirical therapy (HR 3.48), delayed definitive therapy (HR 2.64), and short treatment duration (< 10 days) (HR 5.03). The model demonstrated strong discrimination and calibration. CONCLUSIONS: This study identified significant risk factors associated with 30-day mortality in patients with post-ERCP CRE sepsis and developed a nomogram to accurately predict this risk. This tool enables healthcare practitioners to provide personalized risk assessments and promptly administer appropriate therapies against CRE, thereby reducing mortality rates.

Integrative Effects of Transcutaneous Electrical Acustimulation and Autonomic-Endocrine Mechanisms on Postprocedural Recovery in Patients With Endoscopic Retrograde Cholangio-Pancreatography.

OBJECTIVES: This study aimed to investigate the integrative effects and mechanisms of transcutaneous electrical acustimulation (TEA) on postprocedural recovery from endoscopic retrograde cholangio-pancreatography (ERCP). MATERIALS AND METHODS: A total of 86 patients for elective ERCP were randomly ordered to receive TEA (n = 43) at acupoints PC6 and ST36 or Sham-TEA (n = 43) at sham points from 24 hours before ERCP (pre-ERCP) to 24 hours after ERCP (PE24). Scores of gastrointestinal (GI) motility-related symptoms and abdominal pain, gastric slow waves, and autonomic functions were recorded through the spectral analysis of heart rate variability; meanwhile, circulatory levels of inflammation cytokines of tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 and GI hormones of motilin, ghrelin, cholecystokinin (CCK), and vasoactive intestinal peptide (VIP) were assessed by enzyme-linked immunosorbent assay. RESULTS: 1) TEA, but not Sham-TEA, decreased the post-ERCP GI motility-related symptom score (2.4 ± 2.6 vs 7.9 ± 4.6, p < 0.001) and abdominal pain score (0.5 ± 0.7 vs 4.1 ± 2.7, p < 0.001) at PE24, and decreased the post-ERCP hospital day by 20.0% (p ＜0.05 vs Sham-TEA); 2) TEA improved the average gastric percentage of normal slow waves and dominant frequency by 34.6% and 33.3% at PE24, respectively (both p < 0.001 vs Sham-TEA); 3) TEA, but not Sham-TEA, reversed the ERCP-induced increase of TNF-α but not IL-10 at PE24, reflected as a significantly lower level of TNF-α in the TEA group than in the Sham-TEA group (1.6 ± 0.5 pg/mL vs 2.1 ± 0.9 pg/mL, p ＜ 0.01); 4) compared with Sham-TEA, TEA increased vagal activity by 37.5% (p ＜ 0.001); and 5) TEA caused a significantly higher plasma level of ghrelin (1.5 ± 0.8 ng/ml vs 1.1 ± 0.7 ng/ml, p ＜ 0.05) but not motilin, VIP, or CCK than did Sham-TEA at PE24. CONCLUSION: TEA at PC6 and ST36 accelerates the post-ERCP recovery, reflected as the improvement in GI motility and amelioration of abdominal pain, and suppression of the inflammatory cytokine TNF-α may mediate through both autonomic and ghrelin-related mechanisms.

A new look at the theoretical causes of endometriosis: Narrative review.

Endometriosis is a major health concern in women who have it. Unfortunately, there is no definitive cure except panhysterectomy with its sequelae including induction of premature menopause due to loss of ovaries. Therefore, revealing the causes of this puzzling disease is necessary to avoid contracting it, and to spare women the health disorders resulting from it and the difficulties of treating it. We aimed to study endometriosis with a focus on its theoretical causes. Its classification reports and theories of pathogenesis were identified and studied from available database searches. The causes of endometriosis remain mysterious. Many theories have been proposed to explain the etiology, but retrograde menstruation (RM) remains the closest in this regard. Although this theory is the most accepted in the pathogenesis of endometriosis, its causes are still a matter of debate, especially in women who do not suffer from obstructions to menstrual outflows, such as cases of congenital cervical stenosis and imperforate hymen. It is suggested in some studies that there may be a relationship between women who engage in sexual activity during menstruation and the development of endometriosis. It is concluded that endometriosis is a painful and debilitating disease. Identifying its causes is essential to control the disease and avoid any burdens on health. RM is the main theory for its pathogenesis but its causes are still uncertain. Sexual activity during menstruation may be a possible cause of RM but needs more evidence. Future studies are recommended to reveal all aspects of the pathogenesis of endometriosis.

Is appendoscope a new option for the treatment of acute appendicitis?

Acute appendicitis is a common surgical emergency. It is commonly caused by obstruction of the appendiceal lumen due to fecaliths, tumors, or lymphoid hyperplasia. For over a century, appendectomy has been the primary treatment for acute appendicitis. Abraham Groves performed the first open appendectomy in 1883. In 1983, Kurt Semm completed the first laparoscopic appendectomy, heralding a new era in appendectomy. However, appendectomy is associated with certain complications and a rate of negative appendectomies. Studies have suggested controversy over the impact of appendectomy on the development of inflammatory bowel disease and Parkinson's disease, but an increasing number of studies indicate a possible positive correlation between appendectomy and colorectal cancer, gallstones, and cardiovascular disease. With the recognition that the appendix is not a vestigial organ and the advancement of endoscopic te-chnology, Liu proposed the endoscopic retrograde appendicitis therapy. It is an effective minimally invasive alternative for treating uncomplicated acute appendicitis. Our team has developed an appendoscope with a disposable digital imaging system operated through the biopsy channel of a colonoscope and successfully applied it in the treatment of appendicitis. This article provides an overview of the progress in endoscopic treatment for acute appendicitis and offers a new perspective on the future direction of appendiceal disease treatment.

Clinical efficacy of laparoscopic cholecystectomy plus cholangioscopy for the treatment of cholecystolithiasis combined with choledocholithiasis.

BACKGROUND: Currently, endoscopic retrograde cholangiopancreatography (ERCP) plus laparoscopic cholecystectomy (LC) is the main treatment for cholecystolithiasis combined with choledocholithiasis. However, the treatment is unsatisfactory, and the development of better therapies is needed. AIM: To determine the clinical efficacy of LC plus cholangioscopy for cholecystolithiasis combined with choledocholithiasis. METHODS: Patients (n = 243) with cholecystolithiasis and choledocholithiasis admitted to The Affiliated Haixia Hospital of Huaqiao University (910th Hospital of Joint Logistic Support Force) between January 2019 and December 2023 were included in the study; 111 patients (control group) underwent ERCP + LC and 132 patients (observation group) underwent LC + laparoscopic common bile duct exploration (LCBDE). Surgical success rates, residual stone rates, complications (pancreatitis, hyperamylasemia, biliary tract infection, and bile leakage), surgical indicators [intraoperative blood loss (IBL) and operation time (OT)], recovery indices (postoperative exhaust/defecation time and hospital stay), and serum inflammatory markers [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were compared. RESULTS: No significant differences in surgical success rates and residual stone rates were detected between the observation and control groups. However, the complication rate, IBL, OT, postoperative exhaust/defecation time, and hospital stays were significantly reduced in the observation group compared with the control group. Furthermore, CRP, TNF-α, and IL-6 Levels after treatment were reduced in the observation group compared with the levels in the control group. CONCLUSION: These results indicate that LC + LCBDE is safer than ERCP + LC for the treatment of cholecystolithiasis combined with choledocholithiasis. The surgical risks and postoperative complications were lower in the observation group compared with the control group. Thus, patients may recover quickly with less inflammation after LCBDE.

Revolutionizing palliative care: Electrocautery-enhanced lumen-apposing metal stents in endoscopic-ultrasound-guided biliary drainage for malignant obstructions.

Patients with malignant biliary obstruction, following endoscopic retrograde cholangiopancreatography (ERCP) failure could be referred for endoscopic-ultrasound-guided biliary drainage through electrocautery-enhanced (ECE) lumen-apposing metal stent (LAMS) placement. However, the efficacy and safety of ECE-LAMS in this scenario have remained debatable due to minimal scientific evidence. The current confirmed 91.0% clinical success, 96.7% technical success, 7.3% reintervention rate, and 17.5% adverse events, following the treatment of malignant biliary obstruction with ECE-LAMS delivery. Finally, ECE-LAMS proved to be a generalizable strategy for managing biliary obstruction for patients who were excluded from ERCP.

Unveiling the potential of electrocautery-enhanced lumen-apposing metal stents in endoscopic ultrasound-guided biliary drainage.

This editorial delves into Peng et al's article, published in the World Journal of Gastrointestinal Surgery. Peng et al's meta-analysis investigates the effectiveness of electrocautery-enhanced lumen-apposing metal stents (ECE-LAMS) in ultrasound-guided biliary drainage for alleviating malignant biliary obstruction. Examining 14 studies encompassing 620 participants, the research underscores a robust technical success rate of 96.7%, highlighting the efficacy of ECE-LAMS, particularly in challenging cases which have failed endoscopic retrograde cholangio pancreatography. A clinical success rate of 91.0% underscores its impact on symptom alleviation, while a reasonably tolerable adverse event rate of 17.5% is observed. However, the 7.3% re-intervention rate stresses the need for post-procedural monitoring. Subgroup analyses validate consistent outcomes, bolstering the applicability of ECE-LAMS. These findings advocate for the adoption of ECE-LAMS as an appropriate approach for biliary palliation, urging further exploration in real-world clinical contexts. They offer valuable insights for optimizing interventions targeting malignant biliary obstruction management.

A Case of Coil-Assisted Retrograde Transvenous Obliteration to Treat Colonic Varices.

Colonic variceal bleeding is a rare cause of lower gastrointestinal (GI) bleeding, which carries a high mortality rate. Due to limited data, the optimal management of colonic variceal bleeding is not known. Coil-assisted retrograde transvenous obliteration (CARTO) has been shown to be very effective in managing non-esophageal variceal bleeding, but only a few cases demonstrate its effectiveness in treating colonic variceal bleeding. Here we present a case of colonic variceal bleeding treated with CARTO in order to expand on the limited body of evidence showing its efficacy in effectively treating this rare cause of life-threatening GI bleeding.

Comparative efficacy of different surgical techniques for pediatric urolithiasis-a systematic review and meta-analysis.

Background: Prior research has assessed a range of surgical treatments for pediatric urolithiasis, emphasizing the necessity of tailor-made therapeutic approaches. These studies also show the adaptability of percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), and shock wave lithotripsy (SWL) in managing diverse stone dimensions. The goal of this research was to examine the effectiveness of these varying surgical methods in treating pediatric urolithiasis. Methods: Seven digital databases were explored to gather pertinent studies, following the guidelines established by the PRISMA protocol. The retrieved studies were subsequently scrutinized to draw comparisons between the stone-free rate (SFR) and the rate of complications associated with PCNL, RIRS, and SWL. Results: The SFR evaluation revealed no notable disparity between PCNL and RIRS [odds ratio (OR) 1.43, 95% confidence interval (CI): 0.67-3.05, P=0.36]. However, it was observed that both PCNL and RIRS outperformed SWL in terms of effectiveness (OR 2.51, 95% CI: 1.19-5.29, P=0.02 and OR 2.42, 95% CI: 1.41-4.14, P=0.001 respectively). Regarding the complication rates, no significant differences were observed among the three surgical methods (OR 0.67, 95% CI: 0.49-1.59, P=0.05), albeit with various forms of complications being reported. Certain studies associated PCNL with an elevated rate of complications, specifically urinary tract infections (UTIs) and severe hematuria. Conclusions: Though PCNL and RIRS demonstrated higher effectiveness than SWL in achieving SFR, there was no significant disparity in the rates of complications across all three procedures. The study underscores the significance of personalized treatment plans, taking into account aspects such as the dimension and location of the stone, along with patient-specific characteristics.

Measurement of the distal bile duct density on computed tomography can differentiate choledocholithiasis from a control population.

PURPOSE: Hounsfield unit density of biliary fluid on CT may be a useful clinical marker that has not been described in the literature. This method has been used to differentiate pyonephrosis from hydronephrosis in obstructed collecting systems of the kidney. We aimed to create a user-friendly technique to measure the density of the distal bile duct using CT. The bile duct density of cases with proven choledocholithiasis at ERCP were compared with those of a control group (no biliary pathology). METHODS: A total of 106 patients with proven choledocholithiasis at ERCP and 50 control patients were analysed. The distal bile duct density was calculated using the 4-point and max ellipse methods. Two blinded, independent investigators calculated the bile duct density. RESULTS: The HU is significantly higher in the presence of choledocholithiasis (P < 0.0001). Using the Youden index a cut-off value of 28.6 HU for the 4-point technique is useful to predict the presence of choledocholithiasis (Sensitivity 58%, Specificity 86%). CONCLUSION: Calculation of the distal bile duct density can differentiate choledocholithiasis from a control population. It may be useful alone or as a component of a scoring system to select patients more effectively for intervention. The improved use of CT may also decrease use of MRCP and reduce time to ERCP, which have potential cost benefits.

Nonsteroidal Anti-inflammatory Drugs for the Prevention of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis.

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains the most frequent and severe complication following ERCP, elevating both patient suffering and healthcare costs, and posing challenges to the advancement of ERCP techniques. Empirical evidence supports the prophylactic use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of PEP, especially in high-risk populations, as endorsed by both the American Society for Gastrointestinal Endoscopy (ASGE) and the European Society for Gastrointestinal Endoscopy (ESGE). However, the prophylactic efficacy of NSAIDs in average-risk individuals, alongside the ideal drug selection, dosing, and timing of NSAID administration, remains to be elucidated. Furthermore, the synergistic preventive potential of NSAIDs when integrated with other interventions, such as hydration, pancreatic stenting, somatostatin administration, sublingual nitrate application, and epinephrine, warrants further clarification. In this paper, we conduct an exhaustive review of the prophylactic effect and clinical administration of NSAIDs for PEP. We comprehensively synthesize findings from clinical trials investigating NSAIDs, both in monotherapy and combination regimens, for PEP prevention. Additionally, we scrutinize the current landscape of NSAID usage in clinical practice and evaluate their cost-effectiveness. Future research should concentrate on refining NSAID prophylaxis strategies for PEP in patients at different risk levels, while also enhancing adherence to clinical guidelines and alleviating the issue of NSAID cost inflation.

Endoscopic Retrograde Cholangiopancreatography-Related Procedures for the Differential Diagnosis of Isolated Immunoglobin G4-Related Sclerosing Cholangitis and Perihilar Cholangiocarcinoma.

BACKGROUND/PURPOSE: Differential diagnosis of isolated immunoglobin (Ig)G4-related sclerosing cholangitis (IgG4-SC) and cholangiocarcinoma is challenging. We aimed to clarify the role of endoscopic retrograde cholangiography (ERCP)-related procedures in the differential diagnosis of isolated IgG4-SC and perihilar cholangiocarcinoma (PHCC). METHODS: Seven patients with hilar-type isolated IgG4-SC diagnosed at Hiroshima University Hospital and sixty-five patients with surgically resected invasive PHCC were enrolled, and the diagnostic yields of intraductal ultrasonography (IDUS), peroral cholangioscopy (POCS), and pathological examinations were determined. RESULTS: In six of seven (86%) patients with isolated IgG4-SC, the stricture was in the perihilar bile duct. IDUS showed that symmetrical wall thickening (40% vs. 5%, p = 0.04), homogeneous internal echo (80% vs. 5%, p < 0.001), and smooth outer margins (80% vs. 6%, p < 0.001) were more frequent in isolated IgG4-SC than in PHCC. POCS showed a smooth mucosal surface more frequent in isolated IgG4-SC (75% vs. 7%, p = 0.006). Only one patient had two pathological findings characteristic of IgG4-SC. The sensitivity for diagnosing PHCC was 81% using two or more combined sampling methods. CONCLUSIONS: Pathological examinations have limitations in the differential diagnosis of isolated-IgG4-SC and PHCC, and a diagnostic strategy that combines multiple ERCP-related procedures, including IDUS and POCS, is recommended.

Overexpression of RPOTmp Being Targeted to Either Mitochondria or Chloroplasts in Arabidopsis Leads to Overall Transcriptome Changes and Faster Growth.

The transcription of Arabidopsis organellar genes is performed by three nuclear-encoded RNA polymerases: RPOTm, RPOTmp, and RPOTp. The RPOTmp protein possesses ambiguous transit peptides, allowing participation in gene expression control in both mitochondria and chloroplasts, although its function in plastids is still under discussion. Here, we show that the overexpression of RPOTmp in Arabidopsis, targeted either to mitochondria or chloroplasts, disturbs the dormant seed state, and it causes the following effects: earlier germination, decreased ABA sensitivity, faster seedling growth, and earlier flowering. The germination of RPOTmp overexpressors is less sensitive to NaCl, while rpotmp knockout is highly vulnerable to salt stress. We found that mitochondrial dysfunction in the rpotmp mutant induces an unknown retrograde response pathway that bypasses AOX and ANAC017. Here, we show that RPOTmp transcribes the accD, clpP, and rpoB genes in plastids and up to 22 genes in mitochondria.

Overexpression of the transcription factor ANAC017 results in a genomes uncoupled phenotype under lincomycin.

Over-expression (OE) lines for the ER-tethered NAC transcription factor ANAC017 displayed de-repression of gun marker genes when grown on lincomycin (lin). RNA-seq revealed that ANAC017OE2 plants constitutively expressed greater than 40% of the genes induced in wild-type with lin treatment, including plastid encoded genes ycf1.2 and the gene cluster ndhH-ndhA-ndhI-ndhG-ndhE-psaC-ndhD, documented as direct RNA targets of GUN1. Genes encoding components involved in organelle translation were enriched in constitutively expressed genes in ANAC017OE2. ANAC017OE resulted in constitutive location in the nucleus and significant constitutive binding of ANAC017 was detected by ChIP-Seq to target genes. ANAC017OE2 lines maintained the ability to green on lin, were more ABA sensitive, did not show photo-oxidative damage after exposure of de-etiolated seedlings to continuous light and the transcriptome response to lin were as much as 80% unique compared to gun1-1. Both double mutants, gun1-1:ANAC017OE and bzip60:ANAC017OE (but not single bzip60), have a gun molecular gene expression pattern and result in variegated and green plants, suggesting that ANAC017OE may act through an independent pathway compared to gun1. Over-expression of ANAC013 or rcd1 did not produce a GUN phenotype or green plants on lin. Thus, constitutive ANAC017OE2 establishes an alternative transcriptional program that likely acts through a number of pathways, that is, maintains plastid gene expression, and induction of a variety of transcription factors involved in reactive oxygen species metabolism, priming plants for lin tolerance to give a gun phenotype.