Complicated Reflux Research Articles

Treatment of Morbid Obesity and Hiatal Paraesophageal Hernia by Laparoscopic Roux-en-Y Gastric Bypass

Obesity has been proven to be a significant independent risk factor for hiatal hernia. In morbidly obese patients, the usual techniques to improve gastroesophageal reflux after hiatal hernia repair could have poorer outcomes than in the general population. Laparoscopic Roux-en-Y gastric bypass (LRYGBP) has been demonstrated to be an effective procedure in controlling symptoms and complications of gastroesophageal reflux in these patients. Therefore, LRYGBP is one of the most frequent procedures performed in bariatric surgery. The authors report a case of a 41-year-old man with a body mass index (BMI) of 44.6 kg/m(2) who was diagnosed with giant type III hiatal hernia. A laparoscopic approach for both hiatal hernia repair and LRYGBP was performed. At 6 months follow-up, the patient has lost 30% of excess body weight (BMI 34.4), and there is no evidence of recurrence of the esophageal hernia.

Therapy for vesicoureteral reflux: Antibiotic prophylaxis, urotherapy, open surgery, endoscopic injection, or observation?

Vesicoureteral reflux (VUR) refers to the retrograde flow of urine from the bladder into the ureter and renal pelvis. It generally results from congenital maldevelopment of the ureterovesical junction, although VUR may develop in individuals with abnormally high detrusor pressure. VUR increases a child's susceptibility to pyelonephritis and renal scarring. Treatment goals include the prevention of pyelonephritis, reflux nephropathy, and other complications of reflux. Treatment alternatives include antibiotic prophylaxis, urotherapy (correction of voiding dysfunction), and surgical correction (open, injection therapy, or laparoscopic). Recent studies have challenged the presumed benefit of prophylaxis in children with VUR, while long-term retrospective studies have documented a high rate of hypertension in adults with reflux nephropathy. In addition, the risk of persistent VUR in adulthood is unresolved. These reports have stimulated a reevaluation of the role of various treatment options in children with VUR.

Management der gastroösophagealen Refluxkrankheit (GERD) in der Schwangerschaft

Gastroesophageal reflux disease (GERD) is common during pregnancy. The pathogenesis is a decrease in lower oesophageal sphincter pressure caused by female sex hormones, especially progesterone. The most common symptom of GERD is heartburn. Nevertheless, serious reflux complications during pregnancy are rare. In contrast to non-pregnant patients, GERD during pregnancy should be managed with a step-up algorithm beginning with lifestyle modifications and dietary changes. Antacids or sucralfate are considered the first-line on-demand drug therapy. If symptoms persist, any of the histamine-2-receptor antagonists can be used. Proton pump inhibitors are reserved for women with intractable symptoms or complicated reflux disease. Usually, heartburn during pregnancy resolves soon after delivery but little is known about the late sequelae or, respectively, an influence on subsequent pregnancies. Accordingly a prospective study (longitudinal cohort analysis) is currently underway.

Alarm symptoms of GERD

Heartburn is very common. In the United States, about 20% of adults report experiencing heartburn at least once a week. The practice guidelines for gastroesophageal reflux disease (GERD) recommend diagnostic testing in the presence of alarm symptoms, which include dysphagia, odynophagia, weight loss, gastrointestinal bleeding, and anemia. A detailed history of the pattern, severity, and duration of alarm symptoms is essential. What are the benefits of identifying alarm symptoms in patients with GERD? Does identifying patients with alarm symptoms improve the treatment outcome? The goals of this review are to define the alarm symptoms of GERD, determine their ability to predict reflux complications and upper gastrointestinal malignancy, and develop a management strategy for patients with alarm symptoms.

Surgical options and outcomes in Barrett??s esophagus

Barrett's esophagus is a complication of chronic gastroesophageal reflux that results in the replacement of normal stratified squamous epithelium in the distal esophagus by metaplastic columnar mucosa and it carries a 30-fold to 125-fold risk of progression to esophageal adenocarcinoma. Laparoscopic antireflux surgery has proved durable and effective in treating reflux and reflux-related symptoms in patients with Barrett's esophagus. Recent studies have also focused on the histological changes induced in Barrett's epithelium by antireflux surgery. This article reviews the current literature, analysing the impact of antireflux surgery on both the clinical and the histopathological outcomes. Recent studies have disproved the widely held assumption that, once established, Barrett's esophagus does not change. Antireflux surgery can achieve a regression of intestinal metaplasia to cardiac mucosa in patients with Barrett's esophagus and may thus alter the natural history of the disease.

Gastro‐oesophageal reflux disease: a clinical dilemma

In the present issue of Acta Paediatrica, Vandenplas et al. (1) publish a review article on gastro-oesophageal reflux (GOR) disease and oesophageal impedance, a fairly new procedure that has attracted major attention, specifically in its usefulness in clinical work and in clinical research. GOR is a frequent and challenging paediatric problem. Sometimes, GOR is difficult to diagnose, to treat and to schedule for a sound clinical follow-up. In the individual child it may be impossible to predict the clinical course and the ultimate prognosis although most cases of children with GOR will recover over time. Basically, GOR is a physiological event that occurs in every child, particularly after meals. Many episodes are asymptomatic, brief and limited to the distal oesophagus. However, in some children the reflux is long, associated with severe symptoms and oesophagus mucosa destruction because the protective mechanisms are insufficient. In some children there are inherited structural abnormalities, certain types of hernias and hiatus insufficiency that are of basic importance for the ultimate prognosis. However, in most children with GOR, no such abnormalities are identified. There are many unsolved problems in GOR that relate both to lack of basic knowledge and to non-optimal diagnostic procedures. There are many clinical natural and well-motivated questions that need further exploration to be answered and just a few examples are: What is the effect of small intestinal enteropathy, such as celiac disease or allergic intestinal inflammation on small intestinal motility and gastric emptying and possible development of GOR? Additional studies are needed to evaluate the relation and possible association between GOR with micro- or macro-aspiration and apneas in infants. More research is needed on the relation between blood glucose homeostasis and gastric emptying and eventual development of GOR. The effect and mechanisms between constipation and gastric emptying need to be studied in more depth. Additional basic studies are needed on mucosa protective properties. In many cases, probably the majority of cases, the experienced paediatrician diagnoses GOR based on careful clinical evaluation, but no invasive techniques are used. In selected cases more in-depth investigation is needed, especially if there are nutritional problems or if the diagnosis is uncertain. Such procedures are also indicated if there is a suspicion of reflux complication with mucosa damage, bleeding erosions, cicatrization and difficulties in swallowing. For the individual child that needs evaluation, it is very important to have a reliable and sensitive technique that can be used for diagnostic work and for follow-up during treatment of GOR. The procedures used today for primary diagnosis and follow-up are not optimal. The techniques most commonly used are endoscopy and pH manometry. Endoscopy with oesophageal biopsy is and will probably remain the gold standard to diagnose mucosal damage that is associated with acid reflux. On the other hand, the importance of non-acid reflux for mucosal damage is unclear. pH monitoring, preferably associated with manometry, is one cornerstone in the primary diagnostic work-up and sometimes in the follow-up of the patient. However, pH monitoring has certain limitations. The borderline between normality and abnormality is not sharp and the results of pH monitoring are sometimes difficult to evaluate. The values of references used are actually quite arbitrary and pH monitoring is not useful in non-acid refluxes and during treatment with proton pump inhibitors. Oesophageal intraluminal monitoring impedance is a fairly new and promising technique that is being reviewed in the present issue of Acta Paediatrica by Vandenplas et al. (1). It registers oesophageal events with a probe placed transnasally and connected to a recorder and used in conjunction with pH monitoring. Impedance is determined by the quantity and flux of ions into the tissue and allows detection of the frequency, the duration of reflux episodes and the height of refluxes because monitoring is performed at different levels of the oesophagus. It is a very sensitive method and allows detection of weak refluxes, in both acid and alkaline episodes. The diagnostic sensitivity of impedance may correspond to that of the pH probe in untreated patients, but is superior in patients treated with anti-acid medication. There are pitfalls with the technique, such as the presence of intraluminal air and problems with reproducibility, especially for non-acid reflux. Oesophageal impedance is a costly, time-consuming technique, requiring substantial experience at evaluation, but allowing detection of all reflux events. Today the technique is considered as a clinical research tool. Definitely, there is need for better tools than those used today in evaluating patients with GOR. There is no doubt that the impedance-monitoring technique is interesting and promising for paediatrics. Additional clinical research and methodological work are needed before the method can be used in clinical routine. This is also very clearly underlined in the present review article (1).

The NAD(P)H:quinone oxidoreductase I C609T polymorphism modifies the risk of Barrett esophagus and esophageal adenocarcinoma

PurposeThe role of genetic susceptibility to esophageal adenocarcinoma and its precursor lesion Barrett esophagus has not been fully elucidated. This study investigated the effect of polymorphisms in the manganese superoxide dismutase (MnSOD) and NAD(P)H:quinone oxidoreductase 1 (NQO1) genes in modulating the risk of developing Barrett esophagus or esophageal adenocarcinoma. MethodsA total of 584 patients (146 esophagitis, 200 Barrett esophagus, 144 esophageal adenocarcinoma, and 94 controls) were genotyped for the MnSOD C14T and NQO1 C609T polymorphisms using polymerase chain reaction and restriction fragment length polymorphism analysis. ResultsThe NQO1 TT genotype was less common in Barrett esophagus (2.0%) and esophageal adenocarcinoma (1.4%) patients, compared with both esophagitis patients (7.6%) and controls (5.4%). After adjustment for sex, age, body mass index, reflux symptoms, and smoking status, patients with the homozygous TT genotype had a 4.5-fold decreased risk of developing Barrett esophagus (odds ratio = 0.22, 95% confidence interval = 0.07–0.76, P = 0.01) and a 6.2-fold decreased risk of esophageal adenocarcinoma (odds ratio = 0.16, 95% confidence intervals = 0.03–0.94, P = 0.04) compared with individuals with the TC and CC genotypes. No significant differences between groups were observed for the MnSOD polymorphism (P = 0.289). ConclusionsOverall, the results of this study suggest that the NQO1 TT genotype may offer protection from reflux complications such as Barrett esophagus and esophageal adenocarcinoma.

Bone Morphogenetic Protein 4 Expressed in Esophagitis Induces a Columnar Phenotype in Esophageal Squamous Cells

Barrett's esophagus (BE) is a metaplastic condition in which normal squamous esophageal epithelium is replaced by columnar epithelium. It is proposed that one of the possible mechanisms is dedifferentiation of squamous epithelium into columnar epithelium. The pathophysiology through which this metaplasia occurs is unknown. A recent study by serial analysis of gene expression showed that bone morphogenetic protein 4 (BMP-4) is uniquely expressed in BE. In this study, the role of the BMP pathway in the metaplastic transformation of normal squamous cells into columnar cells was examined. Tissues from patients with esophagitis and BE and in an esophagitis-BE rat model were examined for the activation of the BMP pathway. Short-term cultures of primary normal squamous esophageal cells were treated with BMP-4, and cell biological changes were examined by Western blot analysis, immunohistochemistry, and microarrays. In both human and rat tissues, the BMP pathway proved to be activated in esophagitis and BE. Upon incubation of squamous cell cultures with BMP-4, the cytokeratin expression pattern showed a shift that was consistent with columnar epithelium. Involvement of the BMP pathway was suggested by up-regulation of Phosphorylated-Smad 1/5/8 (P-Smad 1/5/8) that was effectively blocked by Noggin, a BMP antagonist. Comparison of the gene expression profiles of squamous cells, BMP-4-treated squamous cells, and BE cells showed a significant shift in the profile of the BMP-4-treated squamous cells toward that of the cultured BE cells. These results suggest that the BMP pathway could play a role in the transformation of normal esophageal squamous cells into columnar cells.

Sleep-related gastroesophageal reflux: Clinical and physiologic consequences

This review addresses the changes in the physiologic responses to esophageal acid contact that occur during sleep. The importance of these changes is addressed as they pertain to the development of esophagitis and other complications of gastroesophageal reflux. Sleep results in physiologic changes that impair esophageal acid clearance, thereby creating a vulnerability to the complications of reflux. These complications are generally considered secondary to prolonged acid mucosal contact. Sleep-related reflux also disrupts sleep, which may result in clinical complaints of sleep disturbance and significant daytime consequences, such as sleepiness and diminished work performance. The significance of these sleep-related findings is addressed in the context of the diagnosis and treatment of GERD.

Topical Application of Mitomycin‐C in Oesophageal Strictures

Benign oesophageal strictures may occur as a complication of caustic ingestion or severe gastro-oesophageal reflux or as a sequela of oesophageal surgery and other fibrosing conditions. The traditional initial treatment of oesophageal strictures is intraluminal dilation; however, even if frequent, this occasionally may not provide adequate oesophageal lumen capacity or give significant symptom-free intervals, and restricturing after dilation is difficult and challenging. Topical postdilation application of an antifibrotic agent, mitomycin-C, in the treatment of an oesophageal stricture has been described. Eight centres participated, with a total of 16 patients (4 girls), median age 48 (range 0-276) months. The causes of stricture were as follows: caustic (10), post-trachea-oesophageal fistula repair (2), peptic (2), Crohn disease (1), and dystrophic epidermolysis bullosa (1). The median (range) length and diameter of the strictures were as follows: 22 mm (8-50 mm) and 1.5 mm (1-6 mm). Of the 16 patients, 15 had undergone repeated dilations varying from 3 to more than 1000 (daily self-bouginage) before mitomycin-C, and the median interval between dilations was 4 weeks. Mitomycin-C 0.1 mg/mL was applied after dilation for a median time of 3.5 minutes and a median of 3 (1-12) times. Major success, both endoscopic and clinical improvement or cure, occurred in 10 of 16 patients. In 3 of 16 patients the interval period between dilations increased dramatically. Failure of therapy was considered in 3 of 16. All of the patients remained symptom free for a follow-up time of as long as 5 years. Postdilation application of topical mitomycin-C resulted in major success in 62.5% of patients and partial success in 19%, and it may be a useful strategy in oesophageal strictures of differing causes that are refractory to repeated perendoscopic dilation.

Helicobacter pylori, Ethnicity, and the Gastroesophageal Reflux Disease Spectrum: A Study from the East

Ethnic differences in gastroesophageal reflux disease (GERD) and its complications as well as racial variations in the prevalence of Helicobacter pylori infection are well documented. Nevertheless, the association between reflux disease, H. pylori, and race has not been adequately explored. We estimated the strength of the association between H. pylori, ethnicity, and the gastroesophageal reflux disease (GERD) spectrum, including Barrett's esophagus, in Asian patients presenting for endoscopy in a tertiary referral center. Prospectively, we studied 188 consecutive patients with GERD, short- and long-segment Barrett's esophagus, and controls. All patients underwent gastroscopy with gastric biopsies to assess H. pylori, gastritis, and atrophy. CagA status and H. pylori infection were determined by immunoblot assay. The overall prevalence of H. pylori infection was 52.1% (of which 77.6% were cagA(+)) and was lowest in the long-segment Barrett's esophagus group (36.7%) (p = .048). When Barrett's esophagus was present, the length of abnormality was 44.8% shorter in the presence of H. pylori (p = .015). Indians had the highest prevalence of H. pylori (75%) and Malays the lowest (19.6%) (p < .001). In Indians, increased prevalence of H. pylori and cagA-positive strains was associated with reduced severity of GERD (p < .004 and p < .001, respectively), a trend not apparent in the other races. Corpus atrophy, which was almost exclusively associated with H. pylori, was highest in Indians as compared to the other races (p = .013). Presence of H. pylori was associated with a reduced severity of GERD spectrum disease in Asians, especially Indians. H. pylori infection may protect against complicated reflux disease via induction of corpus atrophy.

Targeting the Wnt signaling pathway to treat Barrett’s esophagus

Barrett’s esophagus (BE) is an acquired condition in which the normal squamous epithelium in the distal esophagus is replaced by a metaplastic columnar epithelium, as a complication of chronic gastroesophageal reflux. The clinical significance of this disease is its associated predisposition to esophageal adenocarcinoma (EAC). Recently, and similarly to other human malignancies, the Wnt signaling pathway and its key component β-catenin have been implicated in the carcinogenesis of BE. Although mutations in adenomatous polyposis coli (APC) or β-catenin are rare in EAC, alterations of upstream components, such as overexpression of Wnt2 ligand or downregulation of Wnt antagonists may play dominant roles in the activation of the Wnt pathway. Increasing evidence suggests that inhibiting the Wnt pathway may be a new targeted therapy for the treatment of cancers and could, therefore, be promising for the cure of EAC, which remains a highly lethal disease.

Pneumatic dilation or myotomy for achalasia?

Pneumatic dilation or myotomy for achalasia?

Medical management of gastroesophageal reflux disease

Gastroesophageal reflux disease is a common worldwide disorder. Most patients have typical symptoms of heartburn, regurgitation and exacerbation of symptoms with large meal volumes, fatty meals, recumbency or bending forward. Patients who show typical symptoms for under 10 years may be treated empirically with lifestyle and dietary modifications plus acid-suppressing medications. The recent decrease in cost, established safety and wide availability of proton pump inhibitors make them the best choice for monotherapy. Other medical therapies include antacids, H2 receptor antagonists and prokinetic agents. Patients who have alarm symptoms or long-standing symptoms should have an esophagoscopy to evaluate for complications of reflux. Patients who do not respond to therapy should have a test to confirm the diagnosis of gastroesophageal reflux disease.

Dysphagia-Gastroesophageal Reflux Complex: Complications Due to Dysfunction of Solitary Tract Nucleus-Mediated Vago-Vagal Reflex

We report on the complication of gastroesophageal reflux (GER) in four patients with lower brainstem dysfunction. These patients suffered from perinatal asphyxia, cerebellar hemorrhage, or congenital dysphagia of unknown origin and showed facial nerve palsy, inspiratory stridor due to vocal cord paralysis, central sleep apnea, and dysphagia, in various combinations. Naso-intestinal tube feeding was introduced in all of the patients due to recurrent vomiting and aspiration pneumonia resulting from GER. T2-weighted magnetic resonance (MR) imaging revealed symmetrical high intensity lesions in the tegmentum of the lower pons and the medulla oblongata in two of the patients, and pontomedullary atrophy in another patient. In normal subjects, lower esophageal sphincter contraction is provoked by distension of the gastric wall, through a vago-vagal reflex. Since this reflex arc involves the solitary tract nucleus, where the swallowing center is located, the association of dysphagia and GER in the present patients is thought to result from the lesions in the tegmentum of medulla oblongata. We propose the term "dysphagia-GER complex" to describe the disturbed motility of the upper digestive tract due to lower brainstem involvement. In children with brainstem lesions, neurological assessment of GER is warranted, in addition to the examination of other signs of brainstem dysfunction, including dysphagia and respiratory disturbance.

Reflux events and sleep: Are we vulnerable?

This review addresses the changes in the physiologic responses to esophageal acid contact that occur during sleep. The importance of these changes is addressed as they pertain to the development of esophagitis and other complications of gastroesophageal reflux. Sleep results in physiologic changes that impair esophageal acid clearance, thereby creating a vulnerability to the complications of reflux. These complications are generally considered secondary to prolonged acid mucosal contact. Sleep-related reflux also produces a disruption of sleep, which may result in clinical complaints of sleep disturbance and significant daytime consequences, such as sleepiness and diminished work performance. The significance of these sleep-related findings is addressed as they relate to the diagnosis and treatment of gastroesophageal reflux disease.

Efficacy of Nissen Fundoplication Versus Medical Therapy in the Regression of Low-Grade Dysplasia in Patients With Barrett Esophagus

The aim of this study is to compare the effect of medical and surgical treatment on the history of patients with Barrett esophagus (BE) and histologic evidence of low-grade dysplasia (LGD). BE is a complication of severe gastroesophageal reflux. It is considered a major risk factor for esophageal adenocarcinoma, which may develop through stages from nondysplastic metaplasia to dysplasia (LGD and high-grade dysplasia). Presently, there are no recommended therapeutic guidelines for patients with LGD. Between 1998 through 2003, 6592 patients underwent upper endoscopy; 327 of 6592 (5%) patients had BE, and 35 of 327 (10.7%) had LGD. Nineteen patients with LGD were treated with high-dose proton pump inhibitors, and 16 patients underwent laparoscopic Nissen fundoplication. Endoscopic and histologic follow-up was available in all patients after 18 months. We used multiple logistic regression to examine the effect of the 2 treatments on regression of LGD. LGD was predominant in men (male-to-female ratio: 1.7:1). Mean age was 58 +/- 13.5 years. Sixty percent of patients had no endoscopic evidence of esophagitis. A regression from LGD to BE was observed in 12 of 19 (63.2%) patients in the medical group and in 15 of 16 (93.8%) patients in the surgical group (statistically significant difference). Differences between the 2 groups were statistically significant (P = 0.03). The results of our study suggest that surgical treatment may be more effective than medical therapy to modify the natural history of LGD in patients with BE, perhaps because it not only controls acid but also biliopancreatic reflux into the esophagus.

Barrett’s Esophagus: Pathologic Considerations and Implications for Treatment

Barrett's esophagus (BE) is a complication of chronic reflux that results in the replacement of esophageal squamous epithelium with columnar epithelium. BE is endoscopically recognized and pathologically confirmed. The presence of goblet cells is diagnostic. The pathologist must also determine if dysplasia or invasive cancer is present. Acceptable terms for dysplasia are no dysplasia, indefinite for dysplasia, low-grade dysplasia (LGD), or high-grade dysplasia (HGD). It can be difficult to differentiate HGD from intramucosal cancer (IMC) in an endoscopic biopsy specimen. Treatment based on this differentiation is problematic. Indications for treatment of BE are similar to those of patients without BE. Treatment will not cause clinically significant regression of BE or prevent progression to cancer. Cancer development following successful antireflux surgery is uncommon.

Review article: the management of heartburn in pregnancy

Heartburn is a normal consequence of pregnancy. The predominant aetiology is a decrease in lower oesophageal sphincter pressure caused by female sex hormones, especially progesterone. Serious reflux complications during pregnancy are rare; hence upper endoscopy and other diagnostic tests are infrequently needed. Gastro-oesophageal reflux disease during pregnancy should be managed with a step-up algorithm beginning with lifestyle modifications and dietary changes. Antacids or sucralfate are considered the first-line drug therapy. If symptoms persist, any of the histamine2-receptor antagonists can be used. Proton pump inhibitors are reserved for women with intractable symptoms or complicated reflux disease. All but omeprazole are FDA category B drugs during pregnancy. Most drugs are excreted in breast milk. Of systemic agents, only the histamine2-receptor antagonists, with the exception of nizatidine, are safe to use during lactation.

The Yield and Impact of Upper Endoscopy in a Diverse Population with Refractory GERD

Purpose: Several studies have suggested that EGD may alter the management of patients with reflux symptoms. It remains unclear whether the benefit of EGD is consistent across ethnic groups given the lower prevalence of Barrett's esophagus in minority populations. The aim of this study was to determine the yield of EGD and its impact on the management of GERD in a multi-ethnic cohort with refractory symptoms. Methods: All ambulatory patients who completed upper endoscopy for heartburn between July 2002 and December 2004 in a large municipal hospital were reviewed. The study cohort consisted only of patients with persistent heartburn despite at least 6 weeks of PPI therapy. Pre-procedure demographic and clinical data was collected and patients were grouped according to the presence of alarm symptoms (dysphagia, odynophagia, GI bleeding, weight loss, or iron deficiency anemia). Reflux complications were defined as grade 2 or above esophagitis, Barrett's esophagus >3 cm, or esophageal stricture. GERD management was considered to be altered if there was a change in antisecretory therapy, stricture dilation, Barrett's surveillance initiated, or referral to surgery. Results: A total of 263 patients (mean age 53 ± 12 years) met inclusion criteria of which 33 (13.6%) were Caucasian, 21 (8.6%) were African American, 149 (61.3%) were Hispanic, and 40 (16.5%) were Asian or of Middle Eastern descent. Although reflux complications (RC) were highest among Caucasians compared to non-Caucasians, the difference was not significant (15%vs. 14% p = 0.83). The prevalence of RC in the 78 patients with alarm symptoms was not significantly different from the 185 patients without alarm symptoms (13%vs. 15% p = 0.69). EGD altered GERD management in 35% of patients although only 14% of individuals had RC. The 34 patients with RC were significantly more likely to have any alteration in management compared to the 229 patients without RC (56%vs. 31% p = 0.006). Although the prevalence of RC did not differ according to gender, among those with RC women were significantly more likely to have alteration in management when compared to men (72%vs. 38% p = 0.042). Conclusions: In this diverse population with refractory GERD, reflux complications did not differ according to gender, ethnicity or the presence of alarm symptoms. EGD significantly altered management especially in women with esophageal findings. Further studies to evaluate predictors of reflux complications and gender differences in management in multi-ethnic populations are warranted.