Barrett's esophagus: "All diseases are divine and all are human".

Barrett's esophagus (BE) is a controversial condition. The significance of this condition lies in its premalignant potential, so it is important that clinically applicable biomarkers be identified for early detection and targeted prevention. Dysplasia is currently used as main biomarker, but others most recently surveyed in cancer also include microRNAs. Classically, BE was considered to be an acquired disease related to pathological gastroesophageal acid and bile reflux. However, some cases are associated with genetic predisposition, representing an inherited, familial form of BE. The actual gene, or genes, involved in this condition have not yet been identified. Main therapeutic options include medical treatment and antireflux surgery. Both types of treatment are equally efficient in controlling symptoms and neither is able to cause the metaplastic segment to disappear, which is why the risk of malignancy remains. However, we may use endoscopic radiofrequency to eradicate BE and replace it by the typical squamous epithelium of the esophagus. The currently accepted indications of radiofrequency in BE include low- and high-grade dysplasia, but not Barrett's esophagus without dysplasia. In conclusion, BE may have two different presentations: environmental ("human", reflux) or sporadic BE, which is the most common form, and genetic ("divine", inherited) or familiar BE, less common but with a greater risk for malignancy. As they might be two different diseases, surveillance programs and treatments should also be different.

Is prophylactic gastrectomy indicated for healthy carriers of CDH1 gene mutations associated with hereditary diffuse gastric cancer?

INTRODUCTION: hereditary diffuse gastric cancer (HDGC) is a recently reported hereditary cancer syndrome. Patients with suspected HDGC must be under surveillance via endoscopy and multiple biopsies. As an alternative, some studies suggest prophylactic gastrectomy (PG) for disease carriers. The goal of this article was to report our experience with a CDH1 mutation positive family who underwent PG. PATIENTS AND METHODS: the index case was a 34-year-old female diagnosed with diffuse gastric adenocarcinoma and massive carcinomatosis. There was a family history of gastric adenocarcinoma in seven family members. A genetic study identified the c.1577G>A mutation, in exon 11 of the CDH1 gene via sequencing analysis. RESULTS: this mutation was also present in other six family members, who subsequently underwent prophylactic gastrectomy. The pathology study of resected gastric segments revealed multiple microscopic foci of adenocarcinoma in five of these individuals. These foci were not detected in the multiple endoscopies performed before surgery. CONCLUSIONS: we recommend prophylactic gastrectomy for CDH1 mutation carriers even in the absence of lesions during endoscopic screening.

Histopathological and Immunohistochemical Analysis of the Use of Collagen Dressing as a Reinforcement of Esophagic Anastomosis in a Rat Experimental Model. / Análisis histopatológico e inmunohistoquímico del uso del apósito de colágeno como refuerzo de anastomosis esofágica en un modelo experimental en rata.

INTRODUCTION: One of the most severe complications after esophaguectomy is anastomotic dehiscence. The use of collagen sponges could be an effective way to resolve this complication. Our objective was to perform an experimental model of esophageal anastomosis in rats to study these mechanisms. METHODS: A total of 50 Sprague-Dawley rats were used divided into 2 groups, Tachosil® group (n=25) and control group (n=25). After the section of the abdominal esophagus a single-layer esophago-gastric anastomosis was performed reinforced with 1cm of Tachosil® wrapping the anastomosis in group 1. A functional study was performed using manometry as well as histopathological and immunohistochemical studies for angiogenic, fibrogenic and growth factors. RESULTS: The mortality in our series was 8% in the collagen dressing group, compared to 36% in the control group. When esophageal manometry was performed, the dehiscence pressure was higher in the reinforced anastomosis, On microscopical analysis, in the collagen dressing group a profuse inflammatory reaction with abundant neutrophils and macrophages surrounded by a connective matrix with fibroblasts and blood vessels was observed, The expression of VEGF, FGF1 and FGF2 was noticeably higher in the collagen dressing group. CONCLUSIONS: These results show that the application of collagen dressing facilitates tissue reparation phenomena, and therefore could be very useful as a reinforcement of esophago-gastric anastomosis to prevent dehiscence.

Sustainable Green Extraction of Carotenoid Pigments: Innovative Technologies and Bio-Based Solvents.

Carotenoids are ubiquitous and versatile isoprenoid compounds. The intake of foods rich in these pigments is often associated with health benefits, attributable to the provitamin A activity of some of them and different mechanisms. The importance of carotenoids and their derivatives for the production of foods and health-promotion through the diet is beyond doubt. In the new circular economy paradigm, the recovery of carotenoids in the biorefinery process is highly desirable, for which greener processes and solvents are being advocated for, considering the many studies being conducted at the laboratory scale. This review summarizes information on different extraction technologies (ultrasound, microwaves, pulsed electric fields, pressurized liquid extraction, sub- and supercritical fluid extraction, and enzyme-assisted extraction) and green solvents (ethyl lactate, 2-methyltetrahydrofuran, natural deep eutectic solvents, and ionic liquids), which are potential substitutes for more toxic and less environmentally friendly solvents. Additionally, it discusses the results of the latest studies on the sustainable green extraction of carotenoids. The conclusions drawn from the review indicate that while laboratory results are often promising, the scalability to real industrial scenarios poses a significant challenge. Furthermore, incorporating life cycle assessment analyses is crucial for a comprehensive evaluation of the sustainability of innovative extraction processes compared to industry-standard methods.

Phytoene and Phytoene-Rich Microalgae Extracts Extend Lifespan in C. elegans and Protect against Amyloid-ß Toxicity in an Alzheimer's Disease Model.

Phytoene is a colourless carotenoid widely available from dietary sources and a precursor for the synthesis of other carotenoids. Although present at high concentrations across different tissues, phytoene is largely viewed as not having physiological activity. Here, we utilize the model organism C. elegans to show that phytoene is bioactive and has anti-ageing properties. Supplementation with phytoene protects against oxidative damage and amyloid-ß42 proteotoxicity (a major pathology of Alzheimer's disease), and extends lifespan. We also examine extracts from two microalgae, Chlorella sorokiniana and Dunaliella bardawil. We show that the extracts contain high levels of phytoene, and find that these phytoene-rich extracts have protective effects similar to pure phytoene. Our findings show that phytoene is a bioactive molecule with positive effects on ageing and longevity. Our work also suggests that phytoene-rich microalgae extracts can utilized to produce foods or supplements that promote healthy ageing and prevent the development of chronic age-related diseases.

Predictive value of MicroRNAs in the progression of barrett esophagus to adenocarcinoma in a long-term follow-up study.

OBJECTIVE: The aim of this study is to identify a set of microRNAs (miRNAs) as prognostic molecular biomarkers for the progression of Barrett esophagus (BE) to esophageal adenocarcinoma (EAC) to rationalize the surveillance programs in patients with BE. BACKGROUND: Histological dysplasia is currently used as the main biomarker to identify the BE patients at high risk for developing EAC. Although miRNA expression profiles in BE and EAC have been reported, it has not been established which set of miRNAs could constitute a robust diagnostic test to predict the progression of BE to EAC. METHODS: miRNAs associated with progression of BE to EAC were identified using miRNA sequencing analysis. Further validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed in 2 groups of BE patients who either developed or did not develop adenocarcinoma after at least 5 years of follow-up. RESULTS: Twenty-three miRNAs were identified by miRNA sequencing analysis in the carcinogenesis process associated with BE. qRT-PCR analysis using independent tissue samples confirmed differential expression for 19 of them (miR-let-7c, 7, 146a, 149, 153, 192, 192*, 194, 194*, 196a, 196b, 200a, 203, 205, 215, 424, 625, 625*, and 944). However, only miR-192, 194, 196a, and 196b showed a significantly higher expression in BE samples from patients with progression to EAC compared with those who did not progress to EAC. CONCLUSIONS: These findings suggest that the expression pattern of a modest number of miRNAs in metaplasia biopsies could identify the BE patients at high risk for developing EAC. Therefore, it has potential use for the control and treatment of this malignancy.

Effects of pressurized liquid extraction with dimethyl sulfoxide on the recovery of carotenoids and other dietary valuable compounds from the microalgae Spirulina, Chlorella and Phaeodactylum tricornutum.

The impact of pressurized liquid extraction (PLE) and DMSO concentration (0, 30, 50, 100 %) on the yield of antioxidants and minerals from Chlorella were investigated. The results showed that PLE increased the antioxidant yield. Water extracted more proteins, while with 100 % DMSO more polyphenols, chlorophylls, and carotenoids were obtained. The efficiency coefficient (KPLE) results showed that PLE + 100 % DMSO was more suitable for the recovery of antioxidants and pigments from Chlorella (polyphenols 10.465 mg/g, chlorophyll a 6.206 mg/g, chlorophyll b 3.003 mg/g, carotenoids 0.971 mg/g). Thus, PLE + 100 % DMSO was used for recovery studies on Spirulina, Chlorella, and Phaeodactylum tricornutum. Fucoxanthin, ß-carotene, zeaxanthin, and lutein were the major carotenoids in P. tricornutum, Spirulina, and Chlorella, respectively. Regarding the extraction of minerals, Relative Nutrient Values results were calculated based on Recommended Dietary Allowances. The results indicated that the extracts could be used as a mineral source for different populations.

Long-term follow-up of malignancy biomarkers in patients with Barrett's esophagus undergoing medical or surgical treatment.

OBJECTIVE: This study aims to compare some validated biomarkers of malignancy (Ki-67, p53, and apoptosis) between 2 groups of patients with Barrett's esophagus (BE) undergoing randomly medical or surgical treatment. BACKGROUND: The treatment of choice to prevent the malignant progression of BE remains controversial. Translational studies using biomarkers associated with the metaplasia-tumor pathway could be useful to provide some information in this regard. METHODS: The study group consisted of 45 patients: 20 under medical treatment with 40 mg/day of proton pump inhibitors (PPIs) and 25 after Nissen fundoplication (NFP). After a median follow-up of 8 years (range, 5-10 years), the values of Ki-67, p53, and apoptosis were analyzed in all patients before treatment (n = 45) and then 1 year (n = 45), 3 years (n = 45), 5 years (n = 45), and 10 years (n = 25) afterwards in both groups of treatment. These values were also analyzed in 2 subgroups of patients with successful medical and surgical treatment. RESULTS: Both Ki-67 and p53 remained stable after NFP, whereas they increased progressively in patients under PPIs with statistically significant differences between the 2 groups. Conversely, the apoptotic index increased progressively after NFP and decreased in the patients under PPIs with significant differences at 3, 5, and 10 years of follow-up. On comparing the subgroups of successful treatment the same differences were found. CONCLUSIONS: Barrett's epithelium remains more stable after a long-term follow-up in patients with BE treated surgically than in those under PPIs even in the absence of abnormal rates of acid reflux.

Learning Curve for Laparoscopic Sleeve Gastrectomy: a Cumulative Summation (CUSUM) Analysis.

PURPOSE: Bariatric surgery is currently considered the most effective and durable treatment option for morbid obesity. Laparoscopic sleeve gastrectomy (LSG) has become a popular technique and may currently be the most frequently practiced surgical operation to treat obesity. However, no objective analyses of its learning curve have been reported. OBJECTIVE: to analyze the learning curve for LSG. MATERIALS AND METHODS: We included all LSGs performed in our hospital (University Hospital, Spain; Public Practice) from April 2013 to February 2016. The learning curve for LSG was evaluated using cumulative sum (CUSUM) analysis. All variables among the learning curve phases were compared. RESULTS: According to the CUSUM analysis, the learning curve was divided into three unique phases: early learning (the initial 26 patients), acquisition of skills (the middle 30 patients), and mastery of technique (the final 56 patients). The operative time and gastric stenosis significantly decreased with progression of the learning curve without differences in the 30-day postoperative complication rate, postoperative stay, or weight loss. CONCLUSION: According to this study, the learning curve for LSG can be divided into 3 distinct phases, and about 25 patients are needed to demonstrate an improvement in surgical skill.

Results of the different surgical options for the treatment of cancer of the esophagogastric junction: Review of the evidence. / Resultados de las diferentes opciones quirúrgicas para el tratamiento del cáncer de la unión esofagogástrica. Revisión de la evidencia.

There is significant controversy in the management of cardiac cancer. It seems unanimous that Siewert type I tumors be operated on as cancer of the esophagus and Siewert type III as gastric cancer. However, for "true" cancer of the gastric cardia or Siewert II, the authors do not agree. There is the obvious need for free proximal and distal margins, as well as correct lymphadenectomy. For some, esophagectomy is necessary to perform correct radical oncological surgery, but other authors defend that an abdominal approach is sufficient to perform total gastrectomy and distal esophagectomy. Recent and older papers published do not clarify this issue, and their results are contradictory. Chemotherapy prior to surgery can reduce the size of the tumor and the presence of lymphadenopathies.

High risk of malignancy in familial Barrett's esophagus: presentation of one family.

Barrett's esophagus is an acquired condition fundamentally related to the presence of severe and prolonged pathologic acid and biliary gastro-esophageal reflux. However, genetic factors may also play a role in some cases. The aim of this study is to present 3 generations of a Spanish family with the largest number of members so far reported with Barrett's esophagus or esophageal adenocarcinoma. Of the 24 members of this family studied over 3 generations, 6 patients developed esophageal adenocarcinoma, 4 Barrett's esophagus, 6 clinical symptoms of gastro-esophageal reflux disease without Barrett's esophagus, and 8 were asymptomatic. In conclusion, patients with familial Barrett's esophagus get the disease more severely with a high rate of malignancy and, therefore, the endoscopic surveillance should be closer than in cases of nonfamilial Barrett's esophagus.

Endothelial nitric oxide synthase gene polymorphism in dialysis patients.

Nitric oxide is an important factor in the regulation of vasodilator tone. In vascular cells, NO is synthesized by endothelial nitric oxide synthase, a key enzyme of the endogenous vasodilator system. Some studies have described the interaction between NO and the other factors that promote vasodilatation in vascular smooth muscular cells. Some of those factors are angiotensin-converting enzyme (ACE), transforming growth factor beta (TGF beta), and endothelial oxide nitric synthase (eNOS). Polymorphism that can alter the expression or the function of the eNOS protein has been identified in the eNOS gene in the promoter and codification zones. We studied the Glu298Asp variant of the eNOS gene in 52 hemodialysis (HD) patients, 22 peritoneal dialysis (PD) patients, and 93 healthy controls. Identification of the Glu298Asp variant in exon 7 was performed by enzymatic amplification and restriction fragment length polymorphism (RFLP) analysis. The frequencies of eNOS genotypes in the control group were GG, 39.8%; GT, 43%; and TT, 17.2%. In HD patients, the frequencies were GG, 40.3%; GT, 38.7%; and TT, 21.7%. In PD patients, they were GG, 41.6%; GT, 50%; and TT, 8.6%. No significant differences were seen between the control group and the dialysis patients, or between the HD and the PD patients.

Protein oxidative stress in dialysis patients.

Inflammatory status is observed in patients with chronic renal failure (CRF). The relationship between oxygen free radical production and dialysis could play an important role in protein oxidation. Carbonyl protein plasma level is an important tool in the study of protein stress, and it is related to the arterial intima thickness in the atherosclerosis process. We studied protein oxidative stress in 21 peritoneal dialysis (PD) patients and 42 hemodialysis (HD) patients as compared with 32 undialyzed patients with CRF. Carbonyl protein plasma levels were measured in nanomoles per milligram protein by the ELISA method (Winterbourn et al). Dialysis patients had a higher protein carbonyl content than did CRF patients (0.1265 +/- 0.04 nmol/mg vs. 0.1594 +/- 0.03 nmol/mg, p < 0.0002). Patients on PD had a lower level than patients on HD (0.1452 +/- 0.03 nmol/mg vs. 0.1665 +/- 0.04, p < 0.004). Glucose administration in PD is known to be able to increase glucose degradation products (GDPs) and advanced glycosylation end-products (AGEs) with high carboxylic and oxidative stress. In our study, the carbonyl protein level was higher in HD patients than in PD patients, perhaps because more protein oxidative stress is associated with hemodialysis technique or because the PD patients had greater residual renal function.

[Outpatient monitoring of oesophageal pH with a catheter-free pH-meter (Bravo System). A Study of tolerance, safety and efficacy]. / Monitorización ambulatoria del pH esofágico con pH-metría sin sonda (sistema Bravo(R)). Estudio de tolerancia, seguridad y eficacia.

BACKGROUND AND OBJECTIVE: A new catheter-free outpatient oesophageal pH-meter system (Bravo) has recently been developed. The objective of this study is to test the tolerance, safety and efficacy of the system in the measurement of gastric-oesophageal reflux by comparing it with a conventional pH system. PATIENTS AND METHOD: The study was performed on a control group consisting of 10 healthy volunteers (group 1) and in a group of 40 patients with symptoms of gastric-oesophageal reflux disease (groups 2 and 3). An upper digestive system endoscopy, oesophageal manometry and oesophageal pH measurements with a conventional system and/or with the Bravo catheter-free system, was performed on all patients. All patients who had both tests done (groups 1 and 2) filled in a questionnaire on any physical problems and changes in their daily activity. RESULTS: The test tolerance was higher with the Bravo system in the 9 parameters studied. In the group of healthy volunteers (group 1), the median (range) of the total percentage of pH < 4 was 1.1% (0.5-3.1) with the conventional pH and 1.7% (0-3.4) with the Bravo. When comparing the patients with symptoms of gastric-oesophageal reflux disease (group 2) with those who had only one type of pH measurement made, the acid reflux was significantly higher in patients with Barrett's oesophagus than in the rest of the groups, with conventional pH as well as with the Bravo. If we analyse the patient group with disease due to gastric-oesophageal reflux with those on whom both techniques were used (group 3), 7 of the 10 patients had a pathological reflux that only showed up on measuring pH with the Bravo system. CONCLUSIONS: Catheter-free pH measurements (Bravo) is better tolerated and with better satisfaction for the healthy volunteers and patients than with conventional PH, even, on occasions being more efficient for studying acid reflux due to the lower incidence of negative results.

Very long-term objective evaluation of heller myotomy plus posterior partial fundoplication in patients with achalasia of the cardia.

OBJECTIVE: To present the objectively assessed very long-term results of a prospective study of 149 patients with achalasia of the cardia who underwent Heller myotomy and posterior partial fundoplication. SUMMARY BACKGROUND DATA: Very few studies evaluate objectively the very long-term results to analyze whether the effectiveness of Heller myotomy is maintained with the passing of time. METHODS: The study group consisted of 149 patients who underwent a Heller myotomy plus a posterior partial fundoplication through a laparotomy. The median follow-up was 6 years (range, 1-27 years). Follow-up period was over 10 years in 53 patients and over 15 in 36. Clinical, radiologic, endoscopic, manometric, and pHmetric evaluations were performed postoperatively. RESULTS: Satisfactory results were higher than 90% up to 5 years. From that time on results gradually decreased to a 75% rate after 15 years (P < 0.001) due to either heartburn or dysphagia. Both the esophageal diameter and the mean resting pressure of the lower esophageal sphincter decreased postoperatively with no significant changes during follow-up. Esophagitis appeared in 11% of the patients (47% of them being asymptomatic) and 24-hour pH monitoring showed pathologic rates of acid reflux in 14% of patients, 58% of them being asymptomatic. Both esophagitis and pathologic rates of reflux appeared in >40% of the patients late in the follow-up. CONCLUSION: Results after Heller myotomy plus posterior partial fundoplication deteriorate with time, although we achieved a 75% of satisfactory results after >15 years of follow-up. Our study highlights the importance of life long follow-up and the objective assessment of the results.

Standard antireflux operations in patients who have Barrett's esophagus. Current results.

Several therapeutic options exist for patients who have BE, and treatment should be individualized (Fig. 1). The best option in patients who have a high surgical risk or who reject surgery is lifelong conservative treatment, adjusting the PPI dosage with pH-metric controls. In patients who have a low surgical risk the best option is Nissen fundoplication. Only in cases in which esophageal shortening prevents a tension-free fundoplication from being done is a Collis gastroplasty associated with a fundoplication indicated. Other options may be indicated only in exceptional circumstances: (a) duodenal switch, when, after multiple failures with previous surgery, the approach to the esophagogastric junction is extremely difficult; and (b) esophageal resection, when there is a nondilatable esophageal stenosis and in cases in which the histologic study reveals the presence of high-grade dysplasia. Whatever treatment is used, an endoscopic surveillance program is mandatory, since, with the exception of total esophagectomy, no therapeutic option completely eliminates the risk for progression to adenocarcinoma.

Long-term results of a randomized prospective study comparing medical and surgical treatment of Barrett's esophagus.

OBJECTIVE: To compare the results of medical treatment and antireflux surgery in patients with Barrett's esophagus (BE). SUMMARY BACKGROUND DATA: The treatment of choice in BE is still controversial. Some clinical studies suggest that surgery could be more effective than medical treatment in preventing BE from progressing to dysplasia and adenocarcinoma. However, data from prospective comparative studies are necessary to answer this question. METHODS: One hundred one patients were included in a randomized prospective study, 43 with medical treatment and 58 with antireflux surgery. All patients underwent clinical, endoscopic, and histologic assessment. Functional studies were performed in all the operated patients and in a subgroup of patients receiving medical treatment. The median follow-up was 5 years (range 1-18) in the medical treatment group and 6 years (range 1-18) in the surgical treatment group. RESULTS: Satisfactory clinical results (excellent to good) were achieved in 39 of the 43 patients (91%) undergoing medical treatment and in 53 of the 58 patients (91%) following antireflux surgery. The persistence of added inflammatory lesions was significantly higher in the medical treatment group. The metaplastic segment did not disappear in any case. Postoperative functional studies showed a significant decrease in the median percentage of total time with pH below 4, although 9 of the 58 patients (15%) showed pathologic rates of acid reflux. High-grade dysplasia appeared in 2 of the 43 patients (5%) in the medical treatment group and in 2 of the 58 patients (3%) in the surgical treatment group. In the latter, both patients presented with clinical and pH-metric recurrence. There was no case of malignancy after successful antireflux surgery. CONCLUSIONS: These results show that there are no differences between the two types of treatment with respect to preventing BE from progressing to dysplasia and adenocarcinoma. However, successful antireflux surgery proved to be more efficient than medical treatment in this sense, perhaps because it completely controls acid and biliopancreatic reflux to the esophagus.

Barrett's esophagus without esophageal stricture does not increase the rate of failure of Nissen fundoplication.

OBJECTIVE: To assess whether the presence of Barrett's esophagus (BE) modifies the results of Nissen fundoplication. SUMMARY BACKGROUND DATA: Some authors consider that BE, whether or not there is associated stricture, significantly increases the failure rate of standard antireflux surgery; they recommend using different and more aggressive surgical procedures in all patients with BE. METHODS: One hundred seventy-seven patients with gastroesophageal reflux disease, without esophageal stricture, were included in a retrospective study. Patients were divided into two groups: those with BE (n = 57) and those without BE (n = 120). Nissen fundoplication was performed in all patients by the same surgical team. Clinical, endoscopic, and functional (manometry and 24-hour pH monitoring) results in the two study groups were compared. RESULTS: After a median follow-up of 5 years (range 1-18) in the BE group and 6 years (range 1-18) in the non-BE group, the rate of clinical recurrence was 8% in the BE group and 10% in the non-BE group, with no statistically significant difference. The rate of pH-metric recurrence was the same in both groups (15%). CONCLUSIONS: The presence of BE without esophageal stricture does not increase the rate of failure of Nissen fundoplication.