Pilot studies have indicated that peroral endoscopic myotomy (POEM) might be a safe and effective treatment for achalasia. We performed a prospective, international, multicenter study to determine ...the outcomes of 70 patients who underwent POEM at 5 centers in Europe and North America. Three months after POEM, 97% of patients were in symptom remission (95% confidence interval, 89%–99%); symptom scores were reduced from 7 to 1 ( P < .001) and lower esophageal sphincter pressures were reduced from 28 to 9 mm Hg ( P < .001). The percentage of patients in symptom remission at 6 and 12 months was 89% and 82%, respectively. POEM was found to be an effective treatment for achalasia after a mean follow-up period of 10 months. Clinical Trials Gov Registration number: NCT01405417.
Background
Predictors of poor outcome associated with variceal bleeding remain suboptimal. In patients with cirrhosis, serum lactate combined with Model for End-Stage Liver Disease (MELD-LA) improved ...prediction across heterogeneous populations. However, prognostic properties have not yet been assessed in the context of variceal bleeding.
Aims
We aimed to evaluate the predictive performance of MELD-LA compared to MELD, lactate, and nadir hemoglobin in cirrhosis patients with variceal bleeding.
Methods
In this multicenter study, we identified 472 patients with variceal bleeding from a German primary cohort (University Hospitals Hamburg/Frankfurt/Cologne), and two independent external validation cohorts Veterans Affairs (VA), Baylor University. Discrimination for 30-day mortality was analyzed and scores were compared. MELD-LA was evaluated separately in validation cohorts to ensure consistency of findings.
Results
In contrast to nadir hemoglobin, MELD and peak-lactate at time of bleeding were significantly higher in 30-day non-survivors in the primary cohort (
p
= 0.708;
p
< 0.001). MELD-LA had excellent discrimination for 30-day mortality (AUROC 0.82, 95% CI 0.76–0.88), better than MELD and peak-lactate (AUROC 0.78, 95% CI 0.71–0.84; AUROC 0.73, 95% CI 0.66–0.81). MELD-LA predicted 30-day mortality independently of age, sex, severity of liver disease and vasopressor support (HR 1.29 per 1-point-increase of MELD-LA; 95% CI 1.19–1.41;
p
< 0.001). Similarly, MELD-LA demonstrated excellent discrimination for 30-day mortality in the VA (AUROC = 0.86, 95% CI 0.79–0.93) and Baylor cohort (AUROC = 0.85, 95% CI 0.74–0.95).
Conclusions
MELD-LA significantly improves discrimination of short-term mortality associated with variceal bleeding, compared to MELD, peak-lactate and nadir hemoglobin. Thus, MELD-LA might represent a useful and objective marker for risk assessment and therapeutic intervention in patients with variceal bleeding.
Graphical Abstract
Background Current endoscopic therapy for neoplastic Barrett's oesophagus (BO) consists of complete resection/ablation of all Barrett's tissue including neoplastic lesions. Recurrence seems to be ...frequent after thermal therapy, such as radiofrequency ablation. Objective To analyse long-term recurrence of neoplasia and BO after successful widespread endoscopic mucosal resection (EMR). Design In a retrospective analysis, all patients undergoing widespread EMR of neoplastic BO between 2002 and 2007 at two referral centres were followed for at least 3 years after completion of endotherapy. Recurrence was diagnosed if neoplasia and/or BO were detected following previous successful complete removal, defined as at least two negative endoscopies and biopsies. Results Ninety patients undergoing widespread EMR were included (mean age 63 years; 82 male), 58% of whom underwent additional thermal ablation for minor residual disease. Complete eradication of neoplasia and Barrett's tissue was achieved in 90% of patients. On further follow-up (mean 64.8 months), recurrence of neoplastic and non-neoplastic BO was found in 6.2% and 39.5%, respectively. Recurring neoplasia (3 adenocarcinomas, 1 low-grade and 1 high-grade dysplasia) were found after a median of 44 months (range 38–85) and could be retreated endoscopically. In a multivariate analysis, Barrett's length was the only factor significantly associated with recurrence (OR 2.73). Conclusions Even after seemingly complete endoscopic resection, recurrence of BO is frequent and independent of additional thermal therapy. Due to the possibility of neoplasia recurrence even after long disease-free intervals, follow-up should be extended beyond 5 years.
It is assumed that esophageal adenocarcinoma is the end result of a stepwise disease process that transitions through gastroesophageal reflux disease (GERD) and Barrett's esophagus. The aim of this ...study was to examine at what stage known risk factors exert their influence toward the progression to cancer.
We enrolled 113 consecutive outpatients without GERD, 188 with GERD, 162 with Barrett's esophagus, and 100 with esophageal adenocarcinoma or high-grade dysplasia (HGD). All patients underwent a standard upper endoscopy and completed a standardized questionnaire about their social history, symptoms, dietary habits, and prescribed medications. We used adjusted logistic regression analysis to assess risk factors between each two consecutive disease stages from the absence of reflux disease to esophageal adenocarcinoma.
Overall, male gender, smoking, increased body mass index (BMI), low fruit and vegetable intake, duration of reflux symptoms, and presence of a hiatal hernia were risk factors for cancer/HGD. However, different combinations of risk factors were associated with different disease stages. Hiatal hernia was the only risk factor to be strongly associated with the development of GERD. For GERD patients, male gender, age, an increased BMI, duration of reflux symptoms, and presence of a hiatal hernia were all associated with the development of Barrett's esophagus. Finally, the development of cancer/HGD among patients with Barrett's esophagus was associated with male gender, smoking, decreased fruit and vegetable intake, and a long segment of Barrett's esophagus, but not with age, BMI, or a hiatal hernia.
While some risk factors act predominantly on the initial development of reflux disease, others appear to be primarily responsible for the development of more advanced disease stages.
Background & Aims We investigated rates of detection of proximal serrated lesions in a cohort of average-risk patients undergoing screening colonoscopies. Methods We reviewed results from screening ...colonoscopies performed by attending gastroenterologists at 32 endoscopy centers from 2008–2010. Pathology slides were interpreted at the individual centers. For this analysis, serrated lesions included hyperplastic polyps larger than 10 mm, those interpreted as sessile serrated adenomas (or sessile serrated polyp), and traditional serrated adenomas. Rates of detection for conventional adenomas and serrated lesions were compared among centers. Results A total of 5778 lesions were detected in 7215 screening colonoscopies. Of the 5548 lesions with pathology results, 3008 (54.2%) were conventional adenomas, 350 (6.3%) were serrated, and 232 (4.2%) were proximal serrated. The proportion of colonoscopies with at least 1 proximal serrated lesion was 2.8% (range among centers, 0%–9.8%). The number of serrated lesions per colonoscopy ranged from 0.00–0.11 (average, 0.05 ± 0.25). Overall lesion detection rates correlated with proximal serrated lesion detection rates ( R = 0.91, P < .0001); conventional adenoma and proximal serrated lesion detection rates also correlated ( R = .43, P = .025). The detection rate of proximal serrated lesions differed significantly among centers ( P < .0001); odds ratios for detection ranged from 0–0.79. Some centers' pathologists never identified proximal serrated lesions as sessile serrated adenomas/polyps. Conclusions In an average-risk screening cohort, detection of proximal serrated lesions varied greatly among endoscopy centers. There was also substantial variation among pathologists in identification of sessile serrated adenomas/polyps. Nationally, a significant proportion of proximal serrated lesions may be missed during colonoscopy examination or incorrectly identified during pathology assessment. ClinicalTrials.gov Number: NCT00855348.
Outcomes of endoscopic surveillance after surgery for colorectal cancer (CRC) vary with the incidence and timing of CRC detection at anastomoses or non-anastomoses in the colorectum. We performed a ...systematic review and meta-analysis to evaluate the incidence of CRCs identified during surveillance colonoscopies of patients who have already undergone surgery for this cancer.
We searched PubMed, EMBASE, SCOPUS, and the Cochrane Central Register of Clinical Trials through January 1, 2018 to identify studies investigating rates of CRCs at anastomoses or other locations in the colorectum after curative surgery for primary CRC. We collected data from published randomized controlled, prospective, and retrospective cohort studies. Data were analyzed by multivariate meta-analytic models.
From 2373 citations, we selected 27 studies with data on 15,803 index CRCs for analysis (89% of patients with stage I–III CRC). Overall, 296 CRCs at non-anastomotic locations were reported over time periods of more than 16 years (cumulative incidence, 2.2% of CRCs; 95% confidence interval CI, 1.8%–2.9%). The risk of CRC at a non-anastomotic location was significantly reduced more than 36 months after resection compared with before this time point (odds ratio for non-anastomotic CRCs at 36–48 months vs 6–12 months after surgery, 0.61; 95% CI, 0.37–0.98; P = .031); 53.7% of all non-anastomotic CRCs were detected within 36 months of surgery. One hundred and fifty-eight CRCs were detected at anastomoses (cumulative incidence of 2.7%; 95% CI, 1.9%–3.9%). The risk of CRCs at anastomoses was significantly lower 24 months after resection than before (odds ratio for CRCs at anastomoses at 25–36 months after surgery vs 6–12 months, 0.56; 95% CI, 0.32–0.98; P = .036); 90.8% of all CRCs at anastomoses were detected within 36 months of surgery.
After surgery for CRC, the highest risk of CRCs at anastomoses and at other locations in the colorectum is highest during 36 months after surgery—risk decreases thereafter. Patients who have undergone CRC resection should be evaluated by colonoscopy more closely during this time period. Longer intervals may be considered thereafter.
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Background Preclinical studies have demonstrated the over-the-scope clip (OTSC) to be feasible and safe for closure of gastric, duodenal, and colonic perforations. A retrospective clinical study ...demonstrated the feasibility and preliminary safety of the OTSC for the treatment of GI bleeding and closure of acute GI perforations. Objective Because the OTSC allows rapid and easy endoscopic organ wall closure, we hypothesized that it might be a useful tool to close GI fistulae. Design Case series. Setting Academic medical center. Patients Four consecutive patients with GI fistulae. Interventions In all patients, a 12-mm OTSC, in combination with the dedicated twin grasper, anchor device, or endoscopic suction, was used to facilitate endoscopic closure. Main Outcome Measurements In 2 cases, OTSCs allowed complete closure of a posttraumatic esophagopulmonary fistula and a chronic gastrocutaneous fistula. Leak tests and follow-up examination demonstrated complete leakproof closures. In 1 esophagopulmonary fistula and 1 jejunocutaneous fistula, the initial closure attempts using OTSCs were not successful because of chronic fibrotic changes and scarring at the fistula site. Both OTSCs were removed by using an endoscopic grasping forceps. The mean procedure time was 54 minutes (range 24-93 minutes). There were no procedure-related complications. Limitations Small sample size. Conclusions The OTSC seems to be a feasible device to close chronic fistulae of the GI tract. It can achieve leakproof, full-thickness closure of transmural defects. Nevertheless, in circumstances of severe fibrosis and scarring, complete incorporation of the defect into the applicator cap and successful OTSC application might not be possible.
Abstract
After gastrointestinal resections, leakages can occur, persist despite conventional therapy and result in enterocutaneous fistulae. We developed a combination method using flexible ...endoscopic techniques to seal the enteric orifice with an absorbable plug in addition to a percutaneously and fistuloscopically guided open-pore film drainage (Vac-Plug method). We retrospectively searched our endoscopy database to identify patients treated with the outlined technique. The clinical and pathological data were assessed, the method analyzed and characterized and the technical and clinical success determined. We identified 14 patients that were treated with the Vac-Plug method (4 females, 10 males with a mean age of 56 years, range 50–74). The patients were treated over a time period of 23 days (range 4–119) in between one to thirteen interventions (mean n = 5). One patient had to be excluded due to short follow-up after successful closure. Seventy-seven percent (10/13) were successfully treated with a median follow-up of 453 days (range 35–1246) thereafter. No treatment related complications occurred during the therapy. The data of the analysis showed that the Vac-Plug therapy is safe and successful in a relevant proportion of the patients. It is easy to learn and to apply and is well tolerated. In our opinion, it is a promising addition to the armamentarium of interventional methods of these difficult to treat patients. Of course, its usefulness must be further validated in larger prospective studies.
Like many bacteria,
possesses two DNA translocases that affect chromosome segregation at different steps. Prior to septum closure, nonsegregated DNA is moved into opposite cell halves by SftA, while ...septum-entrapped DNA is rescued by SpoIIIE. We have used single-molecule fluorescence microscopy and tracking (SMT) experiments to describe the dynamics of the two different DNA translocases, the cell division protein FtsA and the glycolytic enzyme phosphofructokinase (PfkA), in real time. SMT revealed that about 30% of SftA molecules move through the cytosol, while a fraction of 70% is septum bound and static. In contrast, only 35% of FtsA molecules are static at midcell, while SpoIIIE molecules diffuse within the membrane and show no enrichment at the septum. Several lines of evidence suggest that FtsA plays a role in septal recruitment of SftA: an
deletion results in a significant reduction in septal SftA recruitment and a decrease in the average dwell time of SftA molecules. FtsA can recruit SftA to the membrane in a heterologous eukaryotic system, suggesting that SftA may be partially recruited via FtsA. Therefore, SftA is a component of the division machinery, while SpoIIIE is not, and it is otherwise a freely diffusive cytosolic enzyme
Our developed SMT script is a powerful technique to determine if low-abundance proteins are membrane bound or cytosolic, to detect differences in populations of complex-bound and unbound/diffusive proteins, and to visualize the subcellular localization of slow- and fast-moving molecules in live cells.
DNA translocases couple the late events of chromosome segregation to cell division and thereby play an important role in the bacterial cell cycle. The proteins fall into one of two categories, integral membrane translocases or nonintegral translocases. We show that the membrane-bound translocase SpoIIIE moves slowly throughout the cell membrane in
and does not show a clear association with the division septum, in agreement with the idea that it binds membrane-bound DNA, which can occur through cell division across nonsegregated chromosomes. In contrast, SftA behaves like a soluble protein and is recruited to the division septum as a component of the division machinery. We show that FtsA contributes to the recruitment of SftA, revealing a dual role of FtsA at the division machinery, but it is not the only factor that binds SftA. Our work represents a detailed
study of DNA translocases at the single-molecule level.
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