Biomedical subjects

Jan Johansson

Publications and source records attributed to Jan Johansson.

At least 19 recordsLinked to original sources

PubMed2006

Wireless esophageal pH monitoring is better tolerated than the catheter-based technique: results from a randomized cross-over trial.

OBJECTIVES: Esophageal pH monitoring using a wireless pH capsule has been suggested to generate less adverse symptoms resulting in improved patient acceptance compared with the catheter-based method although evidence to support this assumption is lacking. The aim of this study was to evaluate and compare the subjective experience of patients undergoing both techniques for esophageal pH monitoring. METHODS: Using a randomized study design, patients referred for esophageal pH testing underwent both wireless and traditional catheter-based 24-h pH recording with a 7-day interval. The wireless pH capsule was placed during endoscopy and followed by 48-h pH recording. All patients answered a questionnaire, including a 10-cm visual analog scale (VAS), which described the perceived severity of symptoms and the degree of interference with normal daily activities during the pH tests. RESULTS: Thirty-one patients, 16 women and 15 men, were included in the analysis. The severity of all adverse symptoms associated with the wireless technique was significantly lower compared with the catheter-based technique (median VAS 2.1 vs 5.1, P < 0.001). Wireless pH recording was associated with less interference with off-work activities and normal daily life, median VAS 0.6 and 0.7 compared with 5.0 and 5.7, respectively, for the catheter-based technique (P < 0.0001). Patients actively working during both tests reported less interference with normal work during the capsule-based test than during the catheter-based pH test (median VAS 0.3 vs 6.8, P= 0.005). Twenty-seven patients (87%) stated that, if they had to undergo esophageal pH monitoring again, they preferred the wireless test over the catheter-based pH test (P < 0.0001). CONCLUSIONS: This randomized study showed that a significant majority of patients undergoing esophageal pH monitoring preferred the wireless pH capsule over the traditional catheter-based technique because of less adverse symptoms and less interference with normal daily life.

Adult↗

PubMed2006

Neuroserpin binds Abeta and is a neuroprotective component of amyloid plaques in Alzheimer disease.

Alzheimer disease is characterized by extracellular plaques composed of Abeta peptides. We show here that these plaques also contain the serine protease inhibitor neuroserpin and that neuroserpin forms a 1:1 binary complex with the N-terminal or middle parts of the Abeta(1-42) peptide. This complex inactivates neuroserpin as an inhibitor of tissue plasminogen activator and blocks the loop-sheet polymerization process that is characteristic of members of the serpin superfamily. In contrast neuroserpin accelerates the aggregation of Abeta(1-42) with the resulting species having an appearance that is distinct from the mature amyloid fibril. Neuroserpin reduces the cytotoxicity of Abeta(1-42) when assessed using standard cell assays, and the interaction has been confirmed in vivo in novel Drosophila models of disease. Taken together, these data show that neuroserpin interacts with Abeta(1-42) to form off-pathway non-toxic oligomers and so protects neurons in Alzheimer disease.

Alzheimer Disease↗

PubMed2006

Acid reflux immediately above the squamocolumnar junction and in the distal esophagus: simultaneous pH monitoring using the wireless capsule pH system.

OBJECTIVES: The pattern of reflux in the most distal esophagus of asymptomatic individuals is largely unknown. Using a wireless technique we compared the degree and the pattern of acid reflux just above the squamocolumnar junction (SCJ) with that measured at the conventional level for pH monitoring. METHODS: Fifty-three asymptomatic volunteers underwent endoscopy with transoral placement of two pH recording capsules, one immediately above and one 6 cm above the SCJ. Ambulatory pH monitoring was performed during 48 h. RESULTS: Three subjects were excluded as the distal capsule was inadvertently placed with the pH electrode below the SCJ. The median percent time with pH < 4 and the median number of reflux episodes were significantly higher immediately above the SCJ compared with that found more proximally (1.6%vs 0.9% and 67 vs 26, p < 0.0001). Of all acid reflux events, 69% were isolated episodes immediately above the SCJ. Only 26% of reflux episodes detected at the SCJ extended to the more proximal pH electrode. Reflux events occurring just above the SCJ were more acidic. The number of reflux events with a minimum pH below 2 or 3 was significantly higher at the SCJ compared with that recorded by the upper capsule (16% and 44%vs 6% and 34%, p < 0.0001). CONCLUSIONS: Conventional pH monitoring substantially underestimates the degree of acid exposure in the most distal esophagus. In healthy subjects, acid exposure immediately above the SCJ was considerably higher and was characterized by shorter reflux episodes that had a lower minimum pH compared with that measured at the traditional level for pH monitoring.

Adult↗

PubMed2006

New synthetic surfactant - how and when?

Animal-derived surfactant preparations are very effective in the treatment of premature infants with respiratory distress syndrome but they are expensive to produce and supplies are limited. In order to widen the indications for surfactant treatment there is a need for synthetic preparations, which can be produced in large quantities and at a reasonable cost. However, development of clinically active synthetic surfactants has turned out to be more complicated than initially anticipated. The hydrophobic surfactant proteins, SP-B and SP-C, which are involved in the adsorption of surface-active lipids to the air-liquid interface of the alveoli and increase alveolar stability, are either too big to synthesize, structurally complex or unstable in pure form. A new generation of synthetic surfactants containing simplified phospholipid mixtures and small amounts of peptides replacing the hydrophobic proteins is currently under development and will in the near future be introduced into the market. However, more trials need to be performed before any conclusions can be drawn about the effectiveness of these synthetic surfactants in relation to natural animal-derived preparations.

Animals↗

PubMed2006

The Brichos domain-containing C-terminal part of pro-surfactant protein C binds to an unfolded poly-val transmembrane segment.

Native lung surfactant protein C (SP-C) is a 4.2-kDa acylpeptide that associates with alveolar surfactant phospholipids via a transmembrane alpha-helix. This helix contains mainly Val, although poly-Val is inefficient in helix formation, and helical SP-C can spontaneously convert to beta-sheet aggregates and amyloid-like fibrils. SP-C is cleaved out from a 21-kDa integral membrane protein, proSP-C, in the alveolar type II cell. Recently several mutations localized in the endoplasmic reticulum-lumenal (C-terminal) part of proSP-C (CTproSP-C) have been associated with intracellular accumulation of toxic forms of proSP-C, low levels of mature SP-C, and development of interstitial lung disease. CTproSP-C contains a approximately 100-residue Brichos domain of unknown function that is also found in other membrane proteins associated with amyloid formation, dementia, and cancer. Here we find that recombinant CTproSP-C binds lipid-associated SP-C, which is in beta-strand conformation, and that this interaction results in an increased helical content. In contrast, CTproSP-C does not bind alpha-helical SP-C. Recombinant CTproSP-C(L188Q), a mutation associated with interstitial lung disease, shows secondary and quaternary structures similar to those of wild type CTproSP-C but is unable to bind lipid-associated beta-strand SP-C. Transfection of CTproSP-C into HEK293 cells that express proSP-C(L188Q) increases the amount of proSP-C protein, whereas no effect is seen on cells expressing wild type proSP-C. These findings suggest that CTproSP-C binds nonhelical SP-C and thereby prevents beta-sheet aggregation and that mutations in CTproSP-C can interfere with this function.

Amino Acid Sequence↗

PubMed2006

N-terminal nonrepetitive domain common to dragline, flagelliform, and cylindriform spider silk proteins.

Spider silk has been extensively studied for its outstanding mechanical properties. Partial intermediate and C-terminal sequences of different spider silk proteins have been determined, and during the past decade also N-terminal domains have been characterized. However, only some of these N-terminal domains have been reported to contain signal peptides, leaving the mechanism whereby they enter the secretory pathway open to speculation. Here we present the sequence of a 394-residue N-terminal region of the Euprosthenops australis major ampullate spidroin 1 (MaSp1). A close comparison with published sequences from other species revealed the presence of N-terminal signal peptides followed by an approximately 130-residue nonrepetitive domain. From secondary structure predictions, helical wheel analysis, and circular dichroism spectroscopy this domain is concluded to contain five alpha-helices and is a conserved constituent of hitherto analyzed dragline, flagelliform, and cylindriform spider silk proteins.

Amino Acid Sequence↗

PubMed2006

Risk factors for complications after esophageal cancer resection: a prospective population-based study in Sweden.

OBJECTIVE: To identify risk factors for complications after resection for esophageal or cardia cancer. SUMMARY BACKGROUND DATA: Knowledge of risk factors for complications after esophageal resection for cancer is sparse, and prospective population-based studies are lacking. METHODS: A prospective, nationwide, population-based study was conducted in Sweden in April 2, 2001 through December 31, 2003. Details about tumor characteristics and stage, surgical procedures, and complications were collected prospectively from the Swedish Esophageal and Cardia Cancer register. Medical records and specific charts from surgical procedures, histopathology reports, and intensive care units were continuously scrutinized. Multivariable logistic regression analyses were used to estimate relative risks and their 95% confidence intervals. RESULTS: Among 275 patients undergoing surgical resection for esophageal or cardia cancer, 122 (44%) had at least one predefined complication. Operation by low-volume surgeons (<5 operations annually) were followed by more anastomotic leakages than those by surgeons with higher volume (odds ratio, 7.86; 95% confidence interval, 2.13-29.00). Hand-sewn and stapled anastomoses did not differ regarding risk of anastomotic leakage. Among cardia cancer patients, transthoracic approach resulted in more respiratory complications compared with transhiatal (abdominal only) approach (odds ratio, 4.78; 95% confidence interval, 1.66-13.76). Older age, adjuvant oncologic therapy, and higher preoperative bleeding volume nonsignificantly increased the risks of complications, while no influence of sex or tumor stage was found. CONCLUSIONS: High-volume esophageal surgeons seem to lower the risk of anastomotic leakage. More large-scale studies are warranted to establish the roles of the other potentially important risk factors suggested in our study.

Adenocarcinoma↗

PubMed2006

Structure and influence on stability and activity of the N-terminal propeptide part of lung surfactant protein C.

Mature lung surfactant protein C (SP-C) corresponds to residues 24-58 of the 21 kDa proSP-C. A late processing intermediate, SP-Ci, corresponding to residues 12-58 of proSP-C, lacks the surface activity of SP-C, and the SP-Ci alpha-helical structure does not unfold in contrast to the metastable nature of the SP-C helix. The NMR structure of an analogue of SP-Ci, SP-Ci(1-31), with two palmitoylCys replaced by Phe and four Val replaced by Leu, in dodecylphosphocholine micelles and in ethanol shows that its alpha-helix vs. that of SP-C is extended N-terminally. The Arg-Phe part in SP-Ci that is cleaved to generate SP-C is localized in a turn structure, which is followed by a short segment in extended conformation. Circular dichroism spectroscopy of SP-Ci(1-31) in microsomal or surfactant lipids shows a mixture of helical and extended conformation at pH 6, and a shift to more unordered structure at pH 5. Replacement of the N-terminal hexapeptide segment SPPDYS (known to constitute a signal in intracellular targeting) of SP-Ci with AAAAAA results in a peptide that is mainly unstructured, independent of pH, in microsomal and surfactant lipids. Addition of a synthetic dodecapeptide, corresponding to the propeptide part of SP-Ci, to mature SP-C results in slower aggregation kinetics and altered amyloid fibril formation, and reduces the surface activity of phospholipid-bound SP-C. These data suggest that the propeptide part of SP-Ci prevents unfolding by locking the N-terminal part of the helix, and that acidic pH results in structural disordering of the region that is proteolytically cleaved to generate SP-C.

Animals↗

PubMed2006

Polymyxin B/pulmonary surfactant mixtures have increased resistance to inactivation by meconium and reduce growth of gram-negative bacteria in vitro.

Pulmonary surfactant is inactivated in meconium aspiration syndrome and neonatal pneumonia. Development of an exogenous surfactant less sensitive to inactivation might be useful for treating these diseases. We investigated in vitro whether addition of the cationic cyclic membrane cross-linking peptide polymyxin B (PxB) and/or calcium chloride (CaCl2) to modified porcine surfactant Curosurf increases resistance to meconium-induced inactivation of surface activity while antimicrobial activity of PxB is maintained. To study bacterial proliferation, Escherichia coli, group B streptococci (GBS), or Staphylococcus aureus were incubated 0-5 h in saline or in meconium in the presence or absence of Curosurf with or without PxB. PxB and CaCl2 improved spreading and adsorption of Curosurf. Curosurf plus CaCl2/PxB needed a 4-fold increase of meconium concentration to increase dynamic surface tension significantly compared with Curosurf plus CaCl2 alone, indicating that PxB further increases the resistance of Curosurf to meconium-induced inactivation. Meconium alone like meconium/Curosurf promoted growth of E. coli and GBS, but addition of Curosurf/PxB or PxB alone significantly reduced the growth of E. coli. Biophysical and antibacterial properties of Curosurf and PxB may be combined into a useful adjunct in the treatment of neonatal Gram-negative pneumonia and/or meconium aspiration syndrome.

Animals↗

PubMed2005

New synthetic surfactants--basic science.

The hydrophobic surfactant proteins, SP-B and SP-C, promote adsorption of surface-active lipids to the air-liquid interface of the alveoli and are essential for alveolar stability and gas exchange. Synthetic surfactant preparations must contain at least one of these hydrophobic proteins, or analogs thereof, to have optimal effects when administered into the airways of patients with lung diseases. However, development of clinically active artificial surfactants has turned out to be more complicated than initially anticipated since the native hydrophobic proteins are structurally complex or unstable in pure form. The proteins have been replaced by different analogs which have the right conformation without forming oligomers. Increased understanding of the surfactant proteins will hopefully lead to development of effective synthetic surfactants which can be produced in large quantities for treatment of a wide range of respiratory disorders. Furthermore, the lipid composition seems to be important, as well as a high lipid concentration in the suspension. For successful treatment of many respiratory diseases, it is also desirable that the synthetic surfactant resists inactivation by plasma components leaking into the alveoli.

Animals↗

PubMed2005

Mapping and analysis of the lytic and fusogenic domains of surfactant protein B.

Surfactant protein B (SP-B) is a hydrophobic, 79 amino acid peptide that regulates the structure and function of surfactant phospholipid membranes in the airspaces of the lung. Addition of SP-B to liposomes composed of DPPC/PG (7:3) leads to membrane binding, destabilization, and fusion, ultimately resulting in rearrangement of membrane structure. The goal of this study was to map the fusogenic and lytic domains of SP-B and assess the effects of altered fusion and lysis on surface activity. Synthetic peptides were generated to predicted helices and/or interhelical loops of SP-B and tested for fusion, lytic, and surface activities. The N-terminal half of SP-B (residues 1-37), which includes the nonhelical N-terminal amino acids in addition to helices 1 and 2, promoted rapid liposome fusion whereas shorter peptides were significantly less effective. The requirements for optimal surface tension reduction were similar to those for fusion; in contrast, helix 1 (residues 7-22) alone was sufficient for liposome lysis. The C-terminal half of SP-B (residues 43-79), which includes helices 3, 4, and 5, exhibited significantly lower levels of fusogenic, lytic, and surface tension reducing activities compared to the N-terminal region. These results indicate that SP-B fusion, lytic and surface activities map predominantly to the N-terminal half of SP-B. Amino acid substitutions in synthetic peptides corresponding to the N-terminal half of SP-B indicated that, in general, decreased fusion or lytic activities were associated with altered surface tension reducing properties of the peptide. However, the presence of fusion and lytic activities alone could not account for the surface tension reducing property of SP-B. We propose a model in which association of helix 1 with lipids leads to membrane permeabilization but not aggregation; helix 2 mediates membrane cross-linking (aggregation), which, in turn, facilitates lipid mixing, membrane fusion, and interfacial adsorption/surface tension reduction.

Amino Acid Sequence↗

PubMed2005

Molecular basis for amyloid fibril formation and stability.

The molecular structure of the amyloid fibril has remained elusive because of the difficulty of growing well diffracting crystals. By using a sequence-designed polypeptide, we have produced crystals of an amyloid fiber. These crystals diffract to high resolution (1 A) by electron and x-ray diffraction, enabling us to determine a detailed structure for amyloid. The structure reveals that the polypeptides form fibrous crystals composed of antiparallel beta-sheets in a cross-beta arrangement, characteristic of all amyloid fibers, and allows us to determine the side-chain packing within an amyloid fiber. The antiparallel beta-sheets are zipped together by means of pi-bonding between adjacent phenylalanine rings and salt-bridges between charge pairs (glutamic acid-lysine), thus controlling and stabilizing the structure. These interactions are likely to be important in the formation and stability of other amyloid fibrils.

Amyloid↗

PubMed2005

Hydrolysis of the amyloid beta-peptide (A beta) 1-40 between Asp23-Val24 produces non-aggregating fragments. An electrospray mass spectrometric study.

The aggregation of full-length (residues 1-40) amyloid beta-peptide (A beta) and fragments corresponding to residues 1-23 and 24-40 was studied by electrospray mass spectrometry, using gramicidin as a non-aggregating reference. Following a lag period, A beta(1-40) at 140 microM concentration aggregates with apparent first-order kinetics. Under acidic conditions A beta(1-40) undergoes spontaneous cleavage between Asp23-Val24 and to a lesser extent also at two other Asp-X motifs. Incubation in acidic H(2)18O showed incorporation of 18O in fragment A beta(1-23), confirming that the Asp23-Val24 peptide bond had been hydrolyzed. Incubation of synthetic A beta(1-23) and A beta(24-40) peptides with A beta(1-40) showed that A beta(24-40) remained in solution for several months, that A beta(1-23) partly disappeared from solution, whereas A beta(1-40) completely disappeared. Further, treatment of sedimentable aggregates formed after co-incubation of the three peptides with hexafluoro-2-propanol or formic acid recovered the intensity of A beta(1-40). These data support previous studies showing that the region of A beta encompassing residues 16-24 is necessary for aggregation into amyloid fibrils.

Amyloid beta-Peptides↗

PubMed2005

Defective mismatch-repair as a minor tumorigenic pathway in Barrett esophagus-associated adenocarcinoma.

The malignant transformation that characterizes the development of Barrett esophagus-associated adenocarcinomas is a multi-step process in which genetic alterations in various tumor-associated genes accumulate. Defective mismatch repair (MMR) is the cause of microsatellite instability (MSI) pathway that characterizes a subset of gastrointestinal tumors and is specifically associated with tumor development within the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. The few studies that have assessed MMR defects in Barrett-associated adenocarcinomas have reached different results. We therefore assessed the expression of the MMR proteins MLH1 and MSH2 in a series of 59 Barrett adenocarcinomas and found a loss of MMR protein immunostaining in 2/59 (3%) tumors; one tumor showed a loss of MSH2 expression, the other tumor showed a loss of MLH1, and both tumors displayed an MSI-high phenotype. Our findings suggest that only a small subset of Barrett adenocarcinomas develop because of defective MMR, but demonstrate that MLH1 and MSH2 are the primary targets for defective MMR also in this tumor type.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Thoracic epidural analgesia or intravenous morphine analgesia after thoracoabdominal esophagectomy: a prospective follow-up of 201 patients.

OBJECTIVE: Thoracoabdominal esophagectomy is a major surgical procedure that carries significant postoperative morbidity and mortality. Because the choice of analgesic technique may influence outcome, the impact of thoracic epidural or intravenous analgesia was investigated after esophagectomy. DESIGN: Prospective observational study during January 1996 until January 2002. SETTING: University hospital. PARTICIPANTS: All patients undergoing thoracoabdominal esophagectomy during the 6-year period. INTERVENTIONS: Patients were prospectively monitored during a 6-year period. Duration of surgery, intraoperative blood loss, fluid administration, postoperative intubation time, intensive care unit (ICU) stay, pain relief and related side effects, postoperative complications, hospital stay, and in-hospital and long-term mortality were compared in relation with the analgesic technique. MEASUREMENTS AND MAIN RESULT: Thoracic epidural analgesia with bupivacaine/morphine was used in 166 patients, and intravenous morphine analgesia was used in 35 patients. Postoperative intubation time and ICU stay were similar in both groups. Patients with epidural analgesia experienced less pain. Sedation, respiratory depression, hallucinations, and confusion were more common in the intravenous morphine group. Postoperative weight did not differ between the groups, despite fluid replacement that was higher in the epidural group during the first 24 hours. The in-hospital mortality rate was 0.5%. CONCLUSIONS: No differences in morbidity/mortality rates depending on analgesic treatment were observed in patients undergoing thoracoabdominal esophagectomy. Thoracic epidural analgesia provided better pain relief with fewer opioid-related side effects than intravenous morphine analgesia. However, postoperative epidural analgesia was associated with more technical difficulties.

Abdomen↗

PubMed2005

Wireless oesophageal pH monitoring: feasibility, safety and normal values in healthy subjects.

OBJECTIVE: A new wireless technique for oesophageal pH monitoring has recently been introduced (Bravo). To implement this technique in clinical practice, values of normal oesophageal acid exposure need to be defined in a large age- and gender-matched healthy population. The aims of this study were to investigate the feasibility and safety of the wireless technique and to establish normal values for oesophageal acid exposure. MATERIALS AND METHODS: Fifty-seven asymptomatic subjects underwent upper gastrointestinal endoscopy with transoral placement of a radio-transmitting capsule 6 cm above the squamocolumnar junction. Oesophageal acid exposure was monitored via a portable receiver during 48 h. RESULTS: Seven men were excluded from the study: capsule dysfunction in 1 and oesophagitis in 6. Fifty subjects (25 M, 25 F, median age 42 years) were included in the study. The radio-transmitting capsule was successfully attached to the oesophageal mucosa in all cases and there were no complications. During pH monitoring 2 capsules were prematurely detached after 32 and 36 h, respectively. The median percentage time with oesophageal pH of less than 4 was 0.7% on day 1 and 1.0% on day 2 (p = 0.033) and the 95th percentile for the 48-h recordings was 4.4%. CONCLUSIONS: Ambulatory pH monitoring using the Bravo system is feasible and appears to be safe. This is the first study to establish normal values for oesophageal acid exposure in a large age- and gender-matched healthy population and offers a basis for the use of the wireless technique in clinical practice.

Adult↗

PubMed2005

Reduction of high cholesterol levels associated with younger age and longer education in a primary health care programme for cardiovascular prevention.

OBJECTIVE: To study possible social predictors for reduction of hyperlipidaemia in subjects offered lifestyle intervention in primary health care after an opportunistic screening. SETTING: Primary health care in Sollentuna, Sweden. DESIGN: Follow-up study of changes in high lipid levels in men and women aged 20-60 years participating in a voluntary screening and cardiovascular prevention programme. SUBJECTS AND MAIN OUTCOME MEASURES: A total of 1904 individuals had a follow-up visit registered after a mean of 466 days. Men and women with raised lipid levels (serum cholesterol = 6.5 mmol/l, and/or triglycerides = 2.3 mmol/l) at baseline were compared with normolipidaemic participants. Data on social characteristics such as education, occupation, marital status, and income were collected from national censuses. Associations between socioeconomic factors and changes in lipid levels were studied. RESULTS: Men and women with hyperlipidaemia were generally (p < 0.001) older (men 6-8 years, women 8-10 years) and less educated than normolipidaemic subjects. Significant predictors for reducing hypercholesterolaemia were younger age, OR 0.97 (0.95-1.00) for increasing age, and longer education, OR 0.47 (0.24-0.91) for low education (<9 years). Foreign-born subjects were more likely to achieve a high success rate in reducing hypercholesterolaemia, OR 3.43 (1.00-11.8), than the Swedish-born. No significant predictors were detected for reduction of high triglyceride levels. CONCLUSION: A successful reduction of high cholesterol levels was associated with younger age and longer education in a primary health care-based programme for cardiovascular prevention.

Adult↗

PubMed2005

Barrett esophagus: risk factors for progression to dysplasia and adenocarcinoma.

OBJECTIVE: To evaluate risk factors for dysplasia and adenocarcinoma development in nondysplastic Barrett mucosa. SUMMARY BACKGROUND DATA: The risk for patients with Barrett esophagus to develop esophageal adenocarcinoma is low, and most patients undergoing surveillance will not develop malignancy. Identification of risk factors may allow for more rational surveillance programs in which patients are stratified according to their individual risk of progressing to dysplasia and invasive adenocarcinoma. METHODS: The development of dysplasia and esophageal adenocarcinoma was studied during long-term endoscopic and histologic surveillance in 140 patients with Barrett esophagus free from dysplasia. Risk factors for progression to dysplasia and adenocarcinoma were evaluated. RESULTS: Median follow-up was 5.8 years. Forty-four patients (31.4%) developed low-grade dysplasia and 7 patients (5%) developed high-grade dysplasia or esophageal adenocarcinoma. Dysplasia development was significantly less common after antireflux surgery compared with conventional medical therapy. Low-grade dysplasia (relative risk = 5.5; 95% confidence interval, 1.1-28.6) and long duration of reflux symptoms (relative risk = 1.3; 95% confidence interval, 1.2-1.7) were independently associated with an increased risk of developing high-grade dysplasia or esophageal adenocarcinoma. CONCLUSIONS: Successful antireflux surgery protects the Barrett mucosa from developing high-grade dysplasia and esophageal adenocarcinoma, possibly by better control of reflux of gastric contents. Low-grade dysplasia is the only clinically useful risk factor that permits stratification of the surveillance intervals according to the risk of the individual patient.

Adenocarcinoma↗