2018 forwards medical reports
More Medical Studies
for Baby’s and Adults
Born unable to Swallow.
Things we find or are sent
by the Doctors themselves.
More Medical Studies
for Baby’s and Adults
Born unable to Swallow.
Things we find or are sent
by the Doctors themselves.
For various esophageal diseases, the search for alternative techniques for tissue repair has led to significant developments in basic and translational research in the field of tissue engineering. Applied to the esophagus, this concept
is based on the in vitro combination of elements judged necessary for in vivo implantation to promote esophageal
tissue remodeling. Different methods are currently being explored to develop substitutes using cells, scaffolds, or a
combination of both, according to the severity of lesions to be treated. In this review, we discuss recent advances
in (1) cell sheet technology for preventing stricture after extended esophageal mucosectomy and (2) full-thickness
circumferential esophageal replacement using tissue-engineered substitutes.
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These tiny organs-in-a-dish help scientists study how organs develop normally, and they’re used to figure out how these body parts go wrong, giving rise to cancer and other disorders. Because they grow in a petri dish, the team can poke and prod them all they want or need. They started with induced pluripotent stem cells, a kind of “master” cell that has the ability to become any other cell in the body. To make them turn into specialized esophagus cells, investigators added a mixture of chemicals and proteins to the stem cells. One key step in this recipe was the gene Sox2 and its associated protein, which have been linked to esophageal conditions. The team found that this gene plays a central role in helping the esophagus develop in a human embryo. The Cincinnati team are already growing a few organoids to help diagnose patients who have medical conditions that affect the esophagus, like congenital birth defects.
Called organoids, these tiny balls of lab-grown tissue resemble a real human esophagus, the researchers report today in the journal Cell Stem Cell. Scientists in Cincinnati USA have even grown a small part of an esophagus made using mature patient tissue as the starting material. And in a first, they did it entirely using human stem cells. In the future, the team hopes to be able to grow organoids that could be transplanted back into patients born with unhealthy or missing esophagus tissue. They say this could also work in adults who have had parts of their esophagus removed due to cancer.
In the long term, they want to make tissue to help the surgeons reconstruct the esophagus in cases where there’s too much missing for the surgeon to correct, they say that’s likely several years away. It’s also possible that esophageal organoids made from stem cells rather than patient tissue may grow bigger or produce more types of cells that occur naturally in the esophagus. Using stem cells as a starting material “may be a major plus, since some patients may lack healthy esophageal tissue from which to try to engineer a new esophagus, BUT before you get too excited one thing that was missing from the esophagus-in-a-dish, for instance: The open space where food and liquids would go, called the lumen.
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New University of Otago research shows infants using popular anti-reflux medicines like omeprazole are not at increased risk of pneumonia or other lower respiratory tract infections, contrary to findings from other international studies.
Lead researcher, Mei-Ling Blank from the Department of Preventive and Social Medicine says use of the drugs – proton pump inhibitors (PPIs) – by otherwise healthy infants is controversial as studies have repeatedly failed to demonstrate the drugs relieve the symptoms of presumed acid reflux in infants.
“Several large overseas studies have observed an association between the use of PPIs and pneumonia in adults, while two small studies conducted overseas suggested that infants using PPIs may also be at risk of lung infections,” Ms. Blank says.
PPIs are commonly prescribed to infants for symptoms attributed to acid reflux or heartburn, with an earlier study by the Otago researchers finding New Zealand has among the highest rates of PPI use by infants internationally.
“Given the high rates of PPI use that one of our earlier studies found, it was important to investigate if infants in New Zealand who were using PPIs were at increased risk of serious lung infections,” Ms. Blank says.
Co-author of the study, Senior Lecturer in Epidemiology in the Department of Preventive and Social Medicine, Dr. Lianne Parkin, says the Otago study was the largest of its kind internationally and was able to address some of the methodological limitations of previous studies.
“Not only did we find a relatively low number of serious lung infections among the children in the cohort, but healthy infants who were currently using PPIs were at no greater risk of a lung infection than healthy infants who had stopped taking PPIs,” Dr. Parkin says.
The study examined the health records of more than 21,000 New Zealand infants born between January 2005 and December 2012 who were dispensed omeprazole, lansoprazole or pantoprazole at least once before their first birthday. The study was published today in the International Journal of Pediatric Gastroenterology and Nutrition.
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Introduction: Successful restoration of digestive continuity following esophagectomy is a challenge. Gastric graft remains is the first option to reconstruct diseased esophagus. However, colon graft is preferable in some instances. Colon interposition is a complex and more demanding surgical procedure. The long-term functional results of colon interposition were satisfactory and can be subsequently affected by late complications. We reported in this retrospective study, the late complications occurred after left colon interposition performed for esophageal caustic stricture from 2000 to 2016.
Patients and Methods: Sixteen of 107 patients who received left colon interposition for esophageal caustic stricture developed a late complication. There were 15 women and one man with median age of 20 years. Three patients had a previous cervical leak and thoracic inlet was widened in 2 cases.
Results: The late post-operative morbidity rate was 14.9%. Cervical anastomotic stricture occurred in 8 patients. Dilations were successful in 6 patients and surgical revision was required in 2 patients. Symptomatic mild gastrocolic reflux occurred in 5 patients and Symptoms improvement had been obtained after medical treatment and lifestyle modification. Two patients developed graft redundancy and surgery was required after failure of life-style modification measures. It consisted of resecting the redundant colon and performing an end-to-end anastomosis.
Conclusion: Late complication after colon interposition can greatly affect swallowing function and quality of life. Surgery is required in some conditions to improve symptoms and life-quality. Identification of predisposing factors and improvement in technique remain the best way to reduce the risk of late complications.
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A 15-year Personal Experience of Esophageal Reconstruction by left colic artery-dependent colic graft for Caustic Stricture: Surgical Technique and Postoperative Results.
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Surgical Outcome of Colon Interposition by the Posterior Mediastinal Route for Thoracic Esophageal Cancer (2007)
For thoracic esophageal cancer patients with a history of gastrectomy, esophageal reconstruction using segments of colon was often accomplished using the anterior mediastinal route to avoid fatal complications related to colon necrosis. Our aim was to review our experience with reconstruction by the posterior mediastinal route and assess the surgical outcomes.
Between 1989 and August 2006, 34 esophageal cancer patients at Akita University Hospital underwent esophageal reconstruction accomplished by colon interposition by the posterior mediastinal route. Data from these patients were reviewed.
Colon conduits consisted of left colon segments in 4 patients and right colon segments in 30. The grafts were supplied with blood by the left colonic artery in 13 patients, the middle colonic artery in 20, and the right colonic artery in 1. The esophagocolic (pharyngocolic) anastomosis was located in the neck in 33 patients (97%) and in the thorax in 1. No patient died during the initial hospital stay. There were no instances of colon necrosis. An anastomotic fistula occurred in 3 patients (9%). Proximal anastomotic strictures occurred in 2 patients (6%). No late graft redundancies resulting in significant dysphagia occurred. Reductions in body weight did not differ from those seen when the gastric tube was used for reconstruction, and alimentary function was good after surgery. The 1-, 2-, 3-, and 5-year survival rates were 66%, 52%, 48%, and 48%, respectively.
Colon interposition by the posterior mediastinal route provides a good outcome and is considered the route of the first choice.
Different respiratory diseases associated with a chronic cough create distinct microbial imbalances in the lower airways of children, according to a study led by researchers at NYU School of Medicine. The study, published online this month in Pediatric Pulmonology, is the first to assess the bacterial population of the airway and gastrointestinal systems of children with a chronic cough using bacterial DNA sequencing.
Up to 20% of preschool-aged children experience a recurring cough lasting longer than four weeks. Unlike an acute cough, which typically lasts fewer than two weeks and is frequently associated with a respiratory tract infection, chronic cough is often related to an underlying respiratory or gastrointestinal issue such as asthma, upper airway disorders, or gastroesophageal reflux disease (GERD).
“A chronic cough can have a significant negative impact on a child’s quality of life, and in order to effectively treat it you must accurately identify the cause,” says lead author Mikhail Kazachkov, MD, clinical professor in the Department of Pediatrics and director of the Division of Pediatric Pulmonology at Hassenfeld Children’s Hospital at NYU Langone. “This first-of-its-kind study could improve assessment and treatment for children with a chronic cough by allowing clinicians to better understand the underlying condition.”
In current practice, clinicians collect fluid or tissue samples and enable bacteria from the sample to grow in a dish to gather information about the airway’s bacterial population and make a diagnosis. With this newer method of 16S ribosomal RNA gene sequencing, researchers were able to capture the presence of key bacterial species in the children’s upper and lower airway and digestive system that were missed by the traditional culture method.
“The disparity between the results of the traditional method of testing and the more unbiased DNA sequencing method further highlights our incomplete knowledge of the microbial populations living in the human body,” says senior author Leopoldo N. Segal, MD, assistant professor in NYU Langone’s Division of Pulmonary, Critical Care, and Sleep Medicine.
The study consisted of 36 children seen at the Pediatric Aerodigestive Center at Hassenfeld Children’s Hospital who had suffered from a daily cough for more than eight weeks. Children were assigned to one of four groups after clinical evaluation: asthma, protracted bacterial bronchitis (PBB), neurologically impaired children fed orally, and neurologically impaired children fed through a tube. Neurologically impaired children are more likely to experience respiratory problems due to a condition’s effect on a child’s muscle strength, breathing, and swallowing.
Researchers collected a total of 354 samples from the children’s airways to their gastrointestinal tracts. They then used genomic and cutting-edge bioinformatic techniques to analyze the millions of pieces of bacterial DNA in the samples, identifying distinct microbial features that were not detectable using the conventional culture method.
Significantly, the microbiomes of neurologically impaired children were strikingly different from children with asthma and bronchitis. The lower airways of orally-fed neurologically impaired children were enriched with Veillonella, bacteria usually found in the mouth, which may point to this bacterium as a marker for aspiration.
In neurologically impaired children, aspiration of food, mucus, or saliva into the lungs is common and can cause rapid development of severe lung disease. This is a growing concern for clinicians, as rates of children with aspiration have risen in recent years due to higher survival rates for children with severe neurological and genetic disorders.
“It is extremely difficult to diagnose aspiration with certainty, but the data give us hope that in the future we can diagnose aspiration-related lung disease using certain microbial signatures, and provide the appropriate treatment to prevent lung damage,” says Dr. Kazachkov.
Researchers also noted that across diagnoses, inflammation of the lower airway was associated with a similarity between the lower airway microbiota and the upper airway microbiota. Researchers suggest that inflammation and associated abundant airway secretions impair the body’s natural microbial clearance, allowing more bacteria to invade the lower airway and further increase its inflammation.
“The characterization of these distinct microbial features is an exciting step toward more personalized targeted therapies for children with varying causes of a chronic cough,” says Dr. Segal.
Researchers acknowledge a limitation of the study is the lack of a control group of healthy children-; ethical concerns making it impossible to perform unnecessary invasive procedures such as bronchoscopy-, and note that further longitudinal studies with larger cohorts are warranted.
While engineered heart tissues can replicate muscle contraction and electrical activity in a dish, many aspects of heart disease can only adequately be captured in 3D. In a report published online yesterday by Nature Biomedical Engineering, researchers describe a scale model of a heart ventricle, built to replicate the chamber’s architecture, physiology, and contractions. Cardiac researchers at Boston Children’s Hospital think it could help them find treatments for congenital heart diseases.
Building a 3D engineered heart ventricle
Collaborators from the Harvard School of Engineering and Applied Sciences (SEAS), the Wyss Institute for Biologically Inspired Engineering, the Harvard Stem Cell Institute and Boston Children’s engineered the ventricles by seeding rat or human heart cells onto 3D nanofiber scaffolds made of biodegradable polyester and gelatin fibers.
Guided by the scaffold, the cells aligned and assembled into beating ventricle chambers. The ventricles’ pressure, volume and contraction rate could be measured as they are in patients. In one test, for example, their beat rate increased when exposed to an adrenaline-like drug.
“The applications, from regenerative cardiovascular medicine to its use as an in vitro model for drug discovery, are wide and varied,” said Kit Parker, PhD, of SEAS, senior author of the study, in a press release.
Studying cardiomyopathies and arrhythmias
Coauthor William Pu, MD, director of Basic and Translational Cardiovascular Research at Boston Children’s, provided the human cells used for the study. He wants to use the engineered ventricles to better understand genetic forms of heart failure and rhythm disturbances that he sees in children with congenital heart disease.
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Dilation is the standard of care for recurrent benign esophageal strictures (BES). Biodegradable stents may prolong the effect of dilation and reduce recurrences. Efficacy and safety of dilation and biodegradable stent placement early in the treatment algorithm of recurrent BES were compared.
This multicenter, randomized study enrolled patients with BES treated with previous dilations to ≥ 16 mm. The primary endpoint was a number of repeat endoscopic dilations for recurrent stricture within 3 and 6 months. Secondary outcomes through 12 months included safety, time to the first dilation for recurrent stricture, dysphagia, and level of activity.
At 3 months, the biodegradable stent group (n = 32) underwent significantly fewer endoscopic dilations for recurrent stricture compared with the dilation group (n = 34; P < 0.001). By 6 months, the groups were similar. The number of patients experiencing adverse events was similar between the groups. Two patients in the biodegradable stent group died after developing tracheoesophageal fistulas at 95 and 96 days post-placement; no deaths were attributed to the stent. Median time to the first dilation of recurrent stricture for the biodegradable stent group was significantly longer (106 vs. 41.5 days; P = 0.003). Dysphagia scores improved for both groups. Patients in the biodegradable stent group had a significantly higher level of activity through 12 months (P < 0.001).
Biodegradable stent placement is associated with a temporary reduction in a number of repeat dilations and prolonged time to recurrent dysphagia compared with dilation. Additional studies are needed to better define the exact role of biodegradable stent placement to treat recurrent BES.
Malignant dysphagia is commonly palliated by placing self-expandable metal stents (SEMS). Although tissue ingrowth into the crevices of the stent leads to better fixation and lower migration rates, recurrent dysphagia from tissue ingrowth can occur with uncovered SEMS. Hence, uncovered stents were replaced with partially covered SEMS (PC-SEMS), where the upper and lower ends of the stents are left uncovered for benign tissue ingrowth to anchor the stent. Reports of secondary dysphagia from tissue ingrowth led to the development of fully covered SEMS (FC-SEMS). However, secondary to lack of tissue ingrowth, higher migration rates were reported with FC-SEMS. Another major difference between PC-SEMS and FC-SEMS is the property of removability (although not yet FDA cleared for this indication). PC-SEMS tend to get embedded with tissue ingrowth; hence, these stents cannot be removed safely as compared with FC-SEMS.
The majority of the studies evaluating these SEMS have been either small case series or nonrandomized, retrospective studies. These authors need to be congratulated for performing this prospective randomized study. A total of 98 patients were randomized 1:1 to either the FC-SEMS or the PC-SEMS. All SEMS were of the woven design, 18 mm in diameter, and similar in all other aspects except for the silicone covering. The primary endpoint measured was recurrent dysphagia, which was observed to be similar in the two groups (19% vs 22%; P = .65). Similarly, dysphagia relief and adverse events were also similar in the two groups. Hence, the authors conclude that fully covering the stent does not offer any additional benefits compared with partially covering it. Because SEMS from only one company were used (woven design), these results cannot be extrapolated to other FC-SEMS such as laser-cut FC-SEMS or fully-covered self-expandable plastic stents.
The low migration rate of the FC-SEMS observed in this study (around 8%) is contrary to what has been published in the literature (up to 40%),1,2 and this may have impacted the results. The reason for this low migration rate is not clear. The authors speculate that the “dog-bone” design of the stent with the covering on the inside may have prevented migration. Besides 4 patients with stent migration, there were an additional 4 patients with recurrent dysphagia in the FC-SEMS group secondary to tissue overgrowth, which was observed only at the proximal end of the stent. Could this have been 2- to 3-cm distal migration of the FC-SEMS rather than “overgrowth,” making a total of 8 of 48 (17%) migrations? Other details—such as how many stents were placed across the GEJ in the two groups, what was the baseline diameter of the stricture in the two groups, was pre-insertion dilatation done, were those with prior SEMS (FC or PC) excluded from enrollment, and what were the reasons of SEMS dysfunction (migration, in-growth, type of stent used)—would have been useful. With similar efficacies of FC-SEMS and PC-SEMS demonstrated in this study, the question is which stent should one use to palliate malignant dysphagia? One deciding factor could be the cost. FC-SEMS tend to be more expensive. Secondly, repositioning the SEMS, as required in 3 patients in this study, is easier with FC-SEMS, especially if needed after a delay of several weeks. Lastly, and an important factor to decide on the type of SEMS, is the need for removing the SEMS.
Although the authors conclude that FC-SEMS do not offer any additional benefits compared with PC-SEMS, there were 4 instances in this study where the authors had to remove the stent: tracheal compression in 1, intractable severe pain in 2, and no relief in 1. FC-SEMS are obviously easier to remove, especially if they are of the woven design as used in this study.
Other reasons to remove SEMS are delayed adverse events. Similar to other studies, both, FC- and PC- SEMS in this study were associated with high adverse events (40% versus 49%, respectively). The longer the stents are in place, more are the chances of developing an adverse event.3 Hence, palliative brachytherapy to relieve dysphagia gave a better quality of life as compared with SEMS in those with longer life expectancy, whereas SEMS were preferable for those with shorter life expectancy.4 However, palliative chemotherapy/chemoradiation can take several weeks to relieve dysphagia unlike SEMS, where the relief is almost immediate. Hence, one approach for those with longer life expectancy can be to place a FC-SEMS to rapidly relieve dysphagia and simultaneously start palliative chemotherapy or chemoradiation or brachytherapy. A few weeks later when palliative therapy takes effect, the SEMS can be removed to prevent delayed SEMS-related adverse events.5 This approach was used in a study by Shin et al, who showed a significant reduction in the incidence of adverse events and the need for re-interventions in those in whom the SEMS was removed after a few weeks during palliative radiotherapy as compared with those in whom the SEMS were not removed.6 PC-SEMS should not be used in anyone for whom there is a likelihood of removing the SEMS at a later date, as they can get embedded into the tissue ingrowth. They may be ideal for those with shorter life expectancy where stent removal is not required and one would not want to risk migration requiring re-intervention.
Covered esophageal self-expandable metal stents (SEMSs) are currently used for palliation of malignant dysphagia. The optimal extent of the covering to prevent recurrent obstruction is unknown. Therefore, we aimed to compare fully covered (FC) versus partially covered (PC) SEMSs in patients with incurable malignant esophageal stenosis.
In this multicenter randomized controlled trial, 98 incurable patients with dysphagia caused by a malignant stricture of the esophagus or cardia were randomized 1:1 to an FC-SEMS or PC-SEMS. The primary outcome was recurrent obstruction after endoscopic SEMS placement. Secondary outcomes were technical and clinical success, adverse events, and health-related quality of life (HRQoL). Patients were followed until 6 months after SEMS placement or to SEMS removal, second SEMS insertion, or death, whichever came first.
Recurrent obstruction after SEMS placement was similar for both types of stents: 19 % for FC-SEMSs and 22 % for PC-SEMSs (P = 0.65). The times to recurrent obstruction did not differ. The frequency of adverse events was similar between the two groups, with major adverse events occurring in 38 % and 47 % of patients for FC-SEMSs and PC-SEMSs, respectively (P = 0.34). No significant differences were seen in technical success, improvement of dysphagia, and HRQoL. Proximal esophageal stenosis and female sex were independently associated with recurrent obstruction and/or major adverse events.
Esophageal FC-SEMSs did not reveal a lower recurrent obstruction rate compared with PC-SEMSs in the palliative management of malignant dysphagia.
BACKGROUND & AIMS
As many as 45% of patients with gastroesophageal reflux disease (GERD) still have symptoms after receiving once-daily proton pump inhibitor (PPI) therapy. We aimed to compare reflux characteristics and patterns between responders and non-responders to once-daily PPI therapy using combined impedance-pH monitoring.
Patients who reported heartburn and/or regurgitation at least twice per week for 3 months while receiving standard-dose PPI therapy were assigned to the PPI failure group (n=16). Patients who reported a complete resolution of symptoms on once-daily PPIs for at least 4 weeks were assigned to the PPI success group (n=13). We collected demographic data and subjects completed the short-form 36 and the GERD health-related quality of life questionnaires. Patients then underwent upper endoscopy and combined esophageal impedance-pH monitoring while on PPI therapy.
Four patients in the PPI success group (31%) and 4 patients in the PPI failure group (25%) had abnormal results from the pH test (P=1.00). Most of the patients in the PPI failure group (75%) were found to have either functional heartburn or reflux hypersensitivity with GERD. Impedance and pH parameters did not differ significantly between the PPI failure and success group.
We found no difference in reflux characteristics between patients with GERD who had successful vs failed once-daily PPI therapy. Most patients in the PPI failure group (75%) had functional esophageal disorders.
Esophageal atresia and tracheoesophageal fistula (EA/TEF) are relatively common malformations in newborns, but the etiology of EA/TEF remains unknown. Fanconi anemia (FA) complementation group A (FANCA) is a key component of the FA core complex and is essential for the activation of the DNA repair pathway. The middle region (amino acids 674-1208) of FANCA is required for its interaction with FAAP20. We performed targeted sequencing of this binding region of FANCA (exons 23-36) in 40 EA/TEF patients.
We also investigated the effect of the p.A958V mutation on the protein-protein interaction between FANCA and FAAP20 using an in vitro binding assay and co-immunoprecipitation. Immunolocalization analysis was performed to investigate the subcellular localization of FANCA, and tissue sections and immunohistochemistry were used to explore the expression of FANCA. We identified four rare missense variants in the FANCA binding region. FANCA mutations were significantly overrepresented in EA/TEF patients compared with 4300 control subjects from the NHLBI-ESP project (Fisher’s exact p = 2.17 × 10, odds ratio = 31.75). p.A958V, a novel de novo mutation in the FANCA gene, was identified in one patient with EA/TEF.
We provide further evidence that the p.A958V mutation reduces the binding affinity of FANCA for FAAP20. Interestingly, the p.A958V mutation impaired the nuclear localization of the FANCA protein expressed in HeLa cells. We found that FANCA was more highly expressed in stratified squamous epithelium than in smooth muscle. In conclusion, mutations in the FANCA gene are associated with EA/TEF in humans.
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