Positive Symptom Index Research Articles

Differences in cerebral response to esophageal acid stimuli and psychological anticipation in GERD subtypes - An fMRI study

BackgroundTo evaluate whether there are differences in the cerebral response to intraesophageal acid and psychological anticipation stimuli among subtypes of gastroesophageal reflux disease (GERD).MethodsThirty nine patients with GERD and 11 healthy controls were enrolled in this study after gastroscopy and 24 hr pH monitoring. GERD subjects were divided into four subgroups: RE (reflux esophagitis), NERD+ (non-erosive reflux disease with excessive acid reflux), NERD-SI+ (normal acid exposure and positive symptom index) and NERD-SI+ (normal acid exposure and negative symptom index, but responded to proton pump inhibitor trial). Cerebral responses to intraesophageal acid and psychological anticipation were evaluated with fMRI.ResultsDuring intraesophageal acid stimulation, the prefrontal cortex (PFC) region was significantly activated in all subgroups of GERD; the insular cortex (IC) region was also activated in RE, NERD+ and NERD-SI- groups; the anterior cingulated cortex (ACC) region was activated only in RE and NERD-SI- groups. The RE subgroup had the shortest peak time in the PFC region after acid was infused, and presented the greatest change in fMRI signals in the PFC and ACC region (P = 0.008 and P = 0.001, respectively). During psychological anticipation, the PFC was significantly activated in both the control and GERD groups. Activation of the IC region was found in the RE, NERD-SI+ and NERD-SI- subgroups. The ACC was activated only in the NERD-SI+ and NERD-SI- subgroups. In the PFC region, the NERD-SI- subgroup had the shortest onset time (P = 0.008) and peak time (P < 0.001). Compared with actual acid infusion, ACC in RE and IC in NERD+ were deactivated while additional areas including the IC and ACC were activated in the NERD-SI+ group; and in NERD-SI- group, onset-time and peak time in the PFC and IC areas were obviously shorter in induced anticipation than in actual acid infusion.ConclusionsThe four subgroups of GERD patients and controls showed distinctly different activation patterns and we therefore conclude GERD patients have different patterns of visceral perception and psychological anticipation. Psychological factors play a more important role in NERD-SI+ and NERD-SI- groups than in RE and NERD+ groups.

Refractory Heartburn: Comparison of Intercellular Space Diameter in Documented GERD vs. Functional Heartburn

Refractory heartburn despite acid suppression may be explained by ongoing gastroesophageal reflux disease (GERD) or functional heartburn (FH), i.e., symptoms without evidence of GERD. Impedance-pH monitoring (impedance-pH) detects acid and nonacid reflux and is useful for evaluating acid-suppressed, refractory patients. Intercellular space diameter (ISD) of esophageal epithelium measured by transmission electron microscopy (TEM) is a marker of epithelial damage present in both erosive and nonerosive reflux disease. ISD has not been used to study refractory heartburn or FH. Our aim was to compare ISD in healthy controls and refractory heartburn patients with GERD and FH. In refractory heartburn patients (heartburn more than twice/week for at least 2 months despite proton pump inhibitor (PPI) b.i.d.), erosive esophagitis and/or abnormal impedance-pH (increased acid exposure or positive symptom index) defined GERD; normal esophagogastroduodenoscopy (EGD)/impedance-pH defined FH. Asymptomatic, healthy controls had normal EGD and pH-metry. Mean ISD in each subject, determined by blinded TEM of esophageal biopsies, was the average of 100 measurements (10 measurements in each of 10 micrographs). In all, 11 healthy controls, 11 FH, and 15 GERD patients were studied. Mean ISD was significantly higher in GERD compared with controls (0.87 vs. 0.32 μm, P=0.003) and FH (0.87 vs. 0.42 μm, P=0.012). Mean ISD was similar in FH and controls (0.42 vs. 0.32 μm, P=0.1). The proportion of patients with abnormal ISD was significantly higher for GERD compared with FH (60 vs. 9%, P=0.014). ISD is increased in refractory heartburn patients with GERD but not those with FH. Our findings suggest that measurement of ISD by TEM might be a useful tool to distinguish GERD from FH in patients with refractory heartburn.

Obese Patients with GERD are More Likely to Have a Positive Symptom Index (SI)

Purpose: Over the last 20 years, there has been a dramatic increase in obesity in the United States. Similarly, the prevalence of GERD has been rising. Specifically, increase in reflux symptoms was reported in obese patients in particular. Aim: To evaluate the Symptom Index (SI) in GERD patients according to their BMI. Methods: Retrospective review of 111 consecutive patients, (76 Female, 68 obese, mean age 49.9 years), who underwent MII-pH for evaluation of their persistent GERD symptoms on PPI therapy. When analyzing symptom associations with reflux, SI is obtained by dividing the number of symptoms occurring within 5 minutes with an MII-pH detected reflux episode by the total number of reported symptoms. SI was considered positive when ≥50%. Only the chief complaint was compared between the two different groups. Patients were on once or twice daily PPI therapy. Results: Symptoms reported were: heartburn, regurgitation, indigestion, nausea, cough and throat clearing. There was a statistically significant difference in SI between both groups, with SI more likely positive in the obese groups (p=0.0072; Mann Whitney test). Conclusion: Obesity not only increases the likelihood of reflux events as shown in previous studies, but also makes it more likely that reported symptoms during MII-pH studies are actually due to MII detected reflux.Table: ResultsFigure

Characteristics of Symptomatic Reflux Episodes in Patients with Non-Erosive Reflux Disease Who Have a Positive Symptom Index on Proton Pump Inhibitor Therapy

Background and Aim: The reason that some reflux episodes evoke symptoms is poorly understood, therefore the aim of this study is to assess the determinants of reflux perception in patients with non-erosive reflux disease (NERD) on proton pump inhibitor (PPI) therapy. Methods: Ten NERD patients with persistent symptoms, despite double-dose PPI therapy, were included in this study. All patients had a positive symptom index (SI), which was determined by ambulatory 24-hour combined impedance-pH monitoring. Reflux episodes were identified and classified as acid, weakly acidic or weakly alkaline reflux and were considered symptomatic if patients recorded a symptom within 5 min after a reflux episode. Results: A total of 954 liquid reflux episodes were detected, including 135 (14.2%) acid, 782 (82.0%) weakly acidic, and 37 (3.9%) weakly alkaline. Overall, 59 (6.2%) reflux episodes were symptomatic and the majority (88.1%) of symptomatic reflux episodes were weakly acidic reflux. When reflux episodes were confined to the distal esophagus, there were very few reflux symptoms. Proximal reflux is significantly more likely to be associated with reflux symptoms, irrespective of the acidity of the refluxate or the duration of proximal reflux episodes. Conclusions: In NERD patients who have a positive SI on double-dose PPI therapy, the high proximal extent of refluxate is a major factor associated with reflux perception.

Predictive Value of Symptoms for Early Detection of Ovarian Cancer

A consensus statement issued by 3 medical organizations in 2007 recommended the use of certain symptoms of ovarian cancer as early diagnostic markers because they were found much more frequently among women with this cancer than in the general population. The recommendation was in close accord with the findings of investigators who had developed a symptom index that could be useful for early diagnosis of ovarian cancer using the symptoms presumably specific for ovarian cancer. Some investigators, however, have questioned the ability of this approach to detect ovarian cancer at an earlier stage or to improve survival. This population-based case-control study evaluated the positive predictive value of a proposed symptom index and of the specific symptoms identified in the consensus recommendation. The study population comprised of women in Washington State aged 35 to 74 years with primary invasive or borderline epithelial ovarian tumors. The data were obtained by in-depth interviews with 812 women (cases) with ovarian cancer who were in a population-based national registry and 1313 control subjects without ovarian cancer who had been selected randomly. A positive symptom index was defined as the presence (at least daily) of one or more symptoms of pelvic or abdominal pain, increased abdominal size or bloating, and difficulty eating or feeling full lasting a week or longer, with an onset l year or less before diagnosis or a reference date (for the control group). Criteria for the consensus recommendations were considered to be met when any of the aforementioned symptoms or urinary urgency or frequency had been present for at least 1 month, with an onset of less than 1 year before diagnosis or a reference date. External estimates of the prevalence of ovarian cancer were used to calculate the positive predictive value. More than 70% of case patients who had a positive index or who fulfilled the consensus criteria did so within 5 months before their diagnosis. Compared to women with late-stage ovarian cancer, those with early-stage ovarian cancer were less likely to have had the symptoms (except nausea). The positive predictive value of the symptoms in women with early-stage ovarian cancer was less than 0.5% and ranged from 0.6% to 1.1% overall for all ages and all stages of invasive disease combined. These findings indicate that use of the symptom patterns to detect ovarian cancer has low positive predictive value and that this approach would be able to diagnose the tumor in only 1 of 100 women in the general population.

935 Effect of mGluR5 Negative Allosteric Modulator (NAM) ADX10059, Monotherapy, on Reflux Events and Lower Esophageal Sphincter (LES) Function in Patients With Gastro-Esophageal Reflux Disease (GERD)

BACKGROUND: In patients with proton pump inhibitors (PPI) resistant reflux symptoms, ambulatory 24-hour pH-impedance monitoring can be used to assess whether a relationship exists between symptoms and reflux episodes. Using this technique we aimed to distinguish patients with hypersensitive esophagus and evaluate the effect of selective serotonin reuptake inhibitors (SSRI) on their symptoms. METHODS: Patients with normal endoscopy and typical reflux symptoms (heartburn, chest pain, regurgitation), despite PPI twice daily, underwent ambulatory 24-hour pH-impedance monitoring. Distal esophageal acid exposure (% time pH < 4) was measured. Reflux episodes were detected by impedance channels located 3, 5, 7, 9, 15 and 17cm above the lower esophageal sphincter (LES) and classified into acid or non-acid based on pH data from 5cm above the LES. A positive symptom index (SI) was declared if at least half of each specific symptom events were preceded by reflux episodes within five minutes. Patients with a normal distal esophageal acid exposure time, but with a positive symptom index for either acid and/or non acid reflux were classified as having hypersensitive esophagus and were randomized to receive citalopram 20mg or placebo once daily for 6 months. Data were analyzed using Fischer's exact test. RESULTS: A total of 84 patients (50 females (59.5%) and 34 males (40.5%); mean age 55 (range 18-75) years) with reflux symptoms despite taking PPI twice daily underwent 24-hour pH-impedance monitoring. Seventy three patients (86.9%) recorded symptoms during the study day, while 35 (47.9%) of those had a positive symptom index for at least one symptom (8 (22.9%) with acid and 27 (77.1%) with non acid reflux). Among those 35 patients, 25 (71.4%) had normal distal esophageal acid exposure time (i.e. hypersensitive esophagus) and were randomized to receive citalopram 20mg (group A, n=13) or placebo (group B, n=12) once daily for a period of 6 months. At the end of the follow up period, 3 out of the 13 patients of group A (23%) and 8 out of the 12 patients of group B (67%) continue to report reflux symptoms (p=0.047). CONCLUSIONS: Treatment with selective serotonin reuptake inhibitors is effective for patients with hypersensitive esophagus as defined by the use of 24-hour pH-impedance monitoring.

934 Selective Serotonin Reuptake Inhibitors for the Treatment of Hypersensitive Esophagus: A Placebo Controlled Study Using Esophageal pH-Impedance Monitoring

BACKGROUND: In patients with proton pump inhibitors (PPI) resistant reflux symptoms, ambulatory 24-hour pH-impedance monitoring can be used to assess whether a relationship exists between symptoms and reflux episodes. Using this technique we aimed to distinguish patients with hypersensitive esophagus and evaluate the effect of selective serotonin reuptake inhibitors (SSRI) on their symptoms. METHODS: Patients with normal endoscopy and typical reflux symptoms (heartburn, chest pain, regurgitation), despite PPI twice daily, underwent ambulatory 24-hour pH-impedance monitoring. Distal esophageal acid exposure (% time pH < 4) was measured. Reflux episodes were detected by impedance channels located 3, 5, 7, 9, 15 and 17cm above the lower esophageal sphincter (LES) and classified into acid or non-acid based on pH data from 5cm above the LES. A positive symptom index (SI) was declared if at least half of each specific symptom events were preceded by reflux episodes within five minutes. Patients with a normal distal esophageal acid exposure time, but with a positive symptom index for either acid and/or non acid reflux were classified as having hypersensitive esophagus and were randomized to receive citalopram 20mg or placebo once daily for 6 months. Data were analyzed using Fischer's exact test. RESULTS: A total of 84 patients (50 females (59.5%) and 34 males (40.5%); mean age 55 (range 18-75) years) with reflux symptoms despite taking PPI twice daily underwent 24-hour pH-impedance monitoring. Seventy three patients (86.9%) recorded symptoms during the study day, while 35 (47.9%) of those had a positive symptom index for at least one symptom (8 (22.9%) with acid and 27 (77.1%) with non acid reflux). Among those 35 patients, 25 (71.4%) had normal distal esophageal acid exposure time (i.e. hypersensitive esophagus) and were randomized to receive citalopram 20mg (group A, n=13) or placebo (group B, n=12) once daily for a period of 6 months. At the end of the follow up period, 3 out of the 13 patients of group A (23%) and 8 out of the 12 patients of group B (67%) continue to report reflux symptoms (p=0.047). CONCLUSIONS: Treatment with selective serotonin reuptake inhibitors is effective for patients with hypersensitive esophagus as defined by the use of 24-hour pH-impedance monitoring.

CC-010 Laying on of the healing hands

Introduction Rumination Syndrome is common yet under-diagnosed and is becoming increasingly recognised in healthy individuals. The primary feature is regurgitation occurring 5–10 min after initiating a meal. It is often confused with disorders such as gastro-oesophageal reflux disease, and patients may be subject to extensive yet unnecessary investigations. Treatment effectiveness with acid reducing medications and prokinetics is limited. The most favourable outcome is achieved with Diaphragmatic Breathing exercises. This case presentation describes the journey of a patient who was found to have rumination syndrome following high-resolution manometry (HRM) and was treated successfully with Diaphragmatic Breathing. Methods HRM (Manoscan 360°, SSI) with 10×5 ml water and 5×1 cm3 solid (bread) swallows and a 250 ml milkshake was performed in the in the upright seated position. This was followed by dual channel 24-h catheter-based pH monitoring. Treatment encompassed two sessions of diaphragmatic therapy. Results HRM: During the bread swallows and after drinking the milkshake, typical symptoms of regurgitation were reproduced. These were associated with short, sharp increases in the intragastric pressure sensors typical of Rumination Syndrome. 24-h Ambulatory reflux study: This exhibited a normal measurement for frequency of reflux events and a positive Symptom Index (87.1%; positive greater than or equal to 50%) for regurgitation. Conclusion Although in this example it was discovered with the use of HRM in a tertiary centre, Rumination Syndrome should be easily diagnosed based only on clinical history. This condition is usually treated with diaphragmatic breathing techniques, however patient commitment to therapy and perseverance is paramount. Diaphragmatic breathing is thought to overwhelm the subconscious yet voluntary abdominal wall muscle contractions which lead to regurgitation, and was successful in this case.

Reflux Events Detected by pH‐MII Do Not Determine Fundoplication Outcome

Because of complications and its invasive nature, fundoplication is often a treatment of last resort for children with gastroesophageal reflux. Gastroesophageal reflux testing does not always predict who will benefit from antireflux surgery. Furthermore, there are no studies to determine whether a higher preoperative reflux burden, including acid and nonacid reflux, is associated with an improved postfundoplication outcome. The aim of the study was to determine predictors of fundoplication outcome including acid and nonacid reflux burden. We retrospectively reviewed preoperative pH-multichannel intraluminal impedance tracings and medical records of 34 patients who underwent fundoplication. Patients were categorized as improved or not improved, and the demographic and reflux characteristics were compared between groups. Multivariate analysis was performed to determine predictors of outcome. No single reflux marker, including the number of acid, nonacid, total events, or the percentage of time that reflux was in the esophagus, predicted fundoplication outcome (P > 0.1). Neither a positive symptom index nor a positive symptom sensitivity index predicted postoperative improvement (P > 0.4). Receiver operating characteristic curve analysis failed to reveal an ideal value to maximize sensitivity for either the symptom index or the symptom sensitivity index. pH-multichannel intraluminal impedance testing may not be a useful tool in predicting fundoplication outcome.

Comparison of Electron Microscopy vs. Light Microscopy for Diagnosing GERD in Patients with Refractory Heartburn

Purpose: In patients with ongoing heartburn despite acid suppression with PPIs, especially in the absence of endoscopic changes, the diagnosis of GERD is challenging and often requires prolonged reflux monitoring. Histological changes attributed to reflux in esophageal biopsies examined by light microscopy (LM) are suboptimal for diagnosing GERD. Dilation of intercellular space distance (ISD) in esophageal epithelium assessed by electron microscopy (EM) is emerging as a robust marker of GERD. Our aim was to compare the sensitivity and specificity of EM vs. LM for the diagnosis of GERD in patients with persistent heartburn despite PPI. Methods: Patients with persistent heartburn despite PPI BID underwent 24 hr-hr ambulatory impedance-pH (MII-pH), and endoscopy (EGD) with biopsies 5 cm above the Z line for analysis by EM and LM. Two schemes with different rigor used to diagnose GERD: “rigorous criteria” were esophagitis on EGD or abnormal MII-pH defined by increased esophageal acid exposure; “less rigorous criteria” added positive symptom index (>50% symptoms associated with reflux) to definition GERD. In both schemes, functional heartburn patients (FH) had normal EGD and MII-pH. Intercellular space distance (ISD) determined blindly by EM at 5,000 magnification using computer-assisted morphometry (Image J software). 10 ISD measurements taken in each of 10 micrographs, mean ISD was the average of 100 measurements. Upper limit of normal ISD was 0.68 μm (the 95th percentile ISD in ten healthy volunteers with normal pH-metry). Light microscopy evaluation performed by single, blinded gastrointestinal pathologist after routine hematoxylin and eosin staining, who provided a diagnosis of GERD based on rete papillae elongation or basal cell hyperplasia. The sensitivity and specificity of EM and LM for GERD were then compared. Results: Use of the more rigorous EGD/MII-pH criteria yielded 6 GERD and 16 FH patients; sensitivity and specificity were 83% and 88% for EM, 67% and of 44% for LM. The less rigorous criteria yielded 12 GERD and 10 FH patients; sensitivity and specificity were 58% and 100% for EM, 67% and 50% for LM. Specificity for GERD appears good for EM and poor for LM. Sensitivity is fair and comparable for EM and LM using less rigorous criteria for GERD, sensitivity is better for EM compared to LM when using more stringent criteria. Conclusion: Increased intercellular space distance measured by Electron Microscopy has good specificity and is thus very reliable (and superior to LM) for excluding GERD in patients with refractory heartburn, providing good accuracy for the diagnosis of functional heartburn. EM has good sensitivity, especially in patients with GERD diagnosed by more rigorous criteria.

Acid and non-acid reflux in Japanese patients with non-erosive reflux disease with persistent reflux symptoms, despite taking a double-dose of proton pump inhibitor: a study using combined pH-impedance monitoring

Combined multi-channel intra-luminal impedance and pH (Mll-pH) monitoring can detect gastro-esophageal reflux and identify acid and non-acid reflux (NAR) events. It can be used for patients with persistent symptoms who are having proton pump inhibitor (PPI) therapy. The aim of this study is to determine the frequency of acid reflux and NAR and to establish their relationship with persistent reflux symptoms in Japanese patients with non-erosive reflux disease (NERD) who are on a double-dose of PPI therapy. Thirteen patients with NERD, with persistent reflux symptoms, despite taking PPI at least twice daily, were included in this study. Twenty-four-hour combined Mll-pH monitoring was carried out on all patients and reflux episodes were detected by impedance channels, located at 3, 5, 7, 9, 15 and 17 cm above the lower esophageal sphincter (LES) and classified into acid reflux and NAR, based on pH data from 5 cm above the LES. A positive symptom index (SI) was declared, if at least half of the symptoms were preceded by reflux episodes within 5 min. A total of 916 liquid reflux episodes were detected, and a total of 171 symptoms were recorded. Eight (4.7%) of 171 symptoms were related to acid reflux, and 68 (39.8%) were related to NAR. Seven (53.8%) patients had a positive SI and in these seven patients, a total of 79 symptoms were recorded. 5 (6.3%) of the 79 symptoms were related to acid reflux and 44 (55.7%) were related to NAR. Persistent reflux symptoms, in SI-positive patients with NERD on double-dose PPI therapy, are more likely to be associated with primarily non-acid reflux.

Intercellular Space Distance Is Increased in Refractory heartburn Patients with GERD but Not Those with Functional heartburn (Fh)

Purpose: Patients with ongoing heartburn despite maximal acid suppression may have objective evidence of GERD on endoscopy or reflux monitoring; those with a negative evaluation are termed Functional Heartburn (FH). Multichannel Intraluminal Impedance and pH (MII-pH) increases the yield of reflux monitoring by assessing both acid and nonacid reflux in acid suppressed patients. Intercellular space distance (ISD) of esophageal epithelium masured by electron microscopy (EM) has recently emerged as a marker of ultrastructural damage. Our aim was to compare ISD in healthy controls and two groups of patients with refractory heartburn: those with evidence of GERD on endoscopy and/or 24-hour MII-pH, and those with Functional Heartburn. Methods: Adult patients with ongoing heartburn despite BID PPI underwent MII-pH on therapy and endoscopy with biopsies for ISD measurement by EM. Patients were categorized as GERD if esophagitis was present on endoscopy or if 24-h MII-pH was abnormal by increased esophageal acid exposure or a positive symptom index (>50% heartburn events associated with a reflux episode). Patients with normal endoscopy and MII-pH were categorized as FH. Healthy controls (no past/present history GERD symptoms, normal 24-h pH monitoring) underwent endoscopy with esophageal biopsies for ISD measurement. ISD in μm determined in all subjects by transmission EM of esophageal biopsies at 5,000× magnification using computer-assisted morphometry (Image J software). 10 measurements of ISD taken in each of 10 fields; mean ISD for each subject was the average of the 100 measurements. Results: 8 healthy controls, 7 FH, and 9 GERD patients studied so far. Two GERD subjects had esophagitis on endoscopy, all other study subjects had normal endoscopy. Results shown in the table. Mean ISD was significantly higher in GERD compared to controls (P= 0.043). Although ISD was numerically higher for GERD compared to FH as well as FH compared to controls, these differences were not statistically significant (type II error is possible). Conclusion: In our preliminary data, GERD but not FH patients with refractory heartburn have increased ISD, even though most GERD patients had normal endoscopy. ISD may be a helpful tool to separate GERD from FH and may help direct therapy in patients not responding to acid suppression, with GERD patients requiring improved reflux control, while FH patients could benefit from non-GERD treatment (e.g. visceral analgesia).Table

Prospective Assessment of Patient Selection for Antireflux Surgery by Combined Multichannel Intraluminal Impedance pH Monitoring

IntroductionSelecting gastroesophageal reflux disease (GERD) patients for surgery on the basis of standard 24-h pH monitoring may be challenging, particularly if this investigation does not correlate with clinical symptoms. Combined multichannel intraluminal impedance pH monitoring (MII-pH) is able to physically detect each episode of intraesophageal bolus movements, enabling identification of either acid or non-acid reflux episodes and thus establish the association of the reflux with symptoms. Materials and MethodsWe prospectively assessed and reviewed data from 314 consecutive patients who underwent MII-pH for GERD not responsive or not compliant to proton pump inhibitor therapy. One hundred fifty-three patients with a minimum follow-up of 1 year constituted the study population. Clinical outcomes and satisfaction rate were collected in all patients who underwent laparoscopic Nissen–Rossetti fundoplication. Outcomes were reported for patients with normal and ineffective peristalsis and for patients with positive pH monitoring, negative pH monitoring and positive total number of reflux episodes at MII, and negative pH monitoring and normal number of reflux episodes at MII and a positive symptom index correlation with MII. ResultsThe overall patient satisfaction rate was 98.3%. No differences were recorded in the clinical outcomes of the patients with preoperative normal and ineffective peristalsis. No differences in patients’ satisfaction and clinical postoperative DeMeester symptom scoring system were noted between the groups as determined by MII-pH. ConclusionMII-pH provides useful information for objective selection of patients to antireflux surgery. Nissen fundoplication provides excellent outcomes in patients with positive and negative pH and positive MII monitoring or Symptom Index association. More extensive studies are needed to definitively standardize the useful MII-pH parameters to select the patient to antireflux surgery.

Combining a symptoms index with CA 125 to improve detection of ovarian cancer

The current study sought to examine whether an index based on the specific pattern of symptoms commonly reported by women with ovarian cancer could be used in combination with CA 125 to improve the sensitivity or specificity of experimental methods of screening for ovarian cancer. A prospective case-control study design was used. Participants included 254 healthy women at high risk for disease because of family history, and 75 women with ovarian cancer. Logistic regression analysis was used to determine whether the symptom index predicted cancer. Symptom index information was found to make a significant independent contribution to the prediction of ovarian cancer after controlling for CA 125 levels (P<.05). The combination of CA 125 and the symptom index identified 89.3% of the women with cancer, 80.6% of the early-stage cancers, and 95.1% of the late-stage cancers. The symptom index identified cancer in 50% of the affected women who did not have elevated CA 125 levels. Unfortunately, 11.8% of the high-risk women without cancer also received a positive symptom index score. The addition of a symptom index to CA 125 created a composite index with a greater sensitivity for the detection of ovarian cancer than CA 125 alone and identified >80% of women with early-stage disease. A composite marker such as this could serve as a first screen in a multistep screening program in which false-positive findings are identified via transvaginal sonography before referral for surgery, leading to an adequate positive predictive value for the multistep program.

Prospective Study Examining the Impact of Multichannel Intraluminal Impedance on Antireflux Surgery

Reflux monitoring using combined multichannel intraluminal impedance (MII) and pH-metry increases the sensitivity for identifying gastroesophageal reflux episodes. The likelihood of a positive symptom index (SI) for patients with reflux disease (gastroesophageal reflux disease [GERD] or nonerosive reflux disease [NERD]) receiving proton pump inhibitor (PPI) treatment has been used to select candidates for antireflux surgery. Little is known about the advantages of MII-pH monitoring compared with pH monitoring alone for evaluating GERD/NERD patients off PPI treatment considered as candidates for antireflux surgery or for assessing changes in MII-pH-detected reflux episodes after antireflux surgery. This study aimed to determine the additional value of MII over pH-metry alone for patients off PPI treatment before and after antireflux surgery. For this study 12 patients (4 women and 8 men; mean age, 45 years; range, 27-74 years) were evaluated using ambulatory MII-pH monitoring before and 3 months after mesh-augmented hiatoplasty. Reflux events were identified by MII-pH (A) and pH-metry (B) as patients recorded symptoms on a data logger. For each symptom, a symptom index was calculated for reflux events identified by MII-pH and by pH-monitoring alone. Preoperatively, MII-pH monitoring identified 71.9 +/- 8.4 reflux episodes, whereas pH monitoring identified only 51.0 +/- 7.8 (p < 0.05). Postoperatively, MII-pH monitoring identified 35.5 +/- 6.6 reflux episodes, whereas pH monitoring identified only 19.6 +/- 4.7 (p < 0.05). The pre- and postoperative symptom index for MII-pH monitoring was higher than pH monitoring (preoperative 91.7% vs 25%, p = 0.006; postoperative 50% vs 16.7%, p = 0.012). Combined MII-pH-metry improves the pre- and postoperative assessment of GERD patients off PPI and results in a higher symptom-reflux association.

Laryngopharyngeal Reflux: Beauty is in The Eye of The Beholder

Laryngopharyngeal Reflux: Beauty is in The Eye of The Beholder

Altered Esophageal Motility and Gastroesophageal Barrier in Patients with Jejunal Interposition After Distal Esophageal Resection for Early Stage Adenocarcinoma

IntroductionLimited resection of the esophagogastric junction has been proven to be safe and oncologically radical in patients with early esophageal cancer. Reconstruction with interposition of isoperistaltic jejunal loop (Merendino procedure) is supposed to prevent gastroesophageal reflux and therefore the recurrence of intestinal metaplasia at the anastomosis. The aim of this study was to assess the frequency of acid and nonacid refluxes after Merendino procedure using multichannel intraluminal impedance-pH (MII-pH) monitoring. Patients and MethodsBetween 2002 and 2005, 12 patients with esophageal adenocarcinoma underwent limited resection and jejunal interposition. Ten patients agreed to undergo a Gastrointestinal Symptom Rating Scale assessment, upper gastrointestinal (GI) endoscopy, esophageal manometry, and combined 24-h MII-pH monitoring more than 10 months postoperatively. ResultsPostoperatively, 4 (40%) patients reported belching without heartburn or acid regurgitation, 3 of them having a positive symptom index during 24-h MII-pH monitoring. Upper GI endoscopy revealed no inflammation, metaplasia, or stenosis at the esophagojejunal anastomosis. Esophageal manometry showed ineffective esophageal motility in four of ten patients. Combined 24-h MII-pH monitoring revealed normal distal esophageal acid exposure (% time pH < 4: 0.1% [0–1.5]), normal number of acid reflux episodes (3 [0–11]) but a high number of nonacid reflux episodes (82 [33–184]). Overall, eight patients revealed an abnormal number of nonacid reflux episodes. ConclusionThe limited resection with jejunal interposition for early esophageal cancer is efficient in controlling acid but not nonacid reflux. While the clinical relevance of nonacid reflux in the recurrence of Barrett’s esophagus is currently unknown, endoscopic surveillance should be considered in these patients.

Combined Multichannel Intraluminal Impedance and pH Esophageal Testing Compared to pH Alone for Diagnosing Both Acid and Weakly Acidic Gastroesophageal Reflux

Twenty-four-hour multichannel intraluminal impedance and pH (MII-pH) esophageal monitoring detects reflux episodes at all pH levels, including acid reflux and weakly acidic reflux (WAR). The aim of this study was to assess the accuracy of pH monitoring alone in detecting acid reflux and WAR compared with MII-pH. For the detection of acid reflux: 60 consecutive MII-pH studies of patients off acid suppression were included. All studies initially were read by exclusively analyzing pH tracing for acid reflux episodes. Subsequently, all studies were blindly read again analyzing MII-pH-detected acid reflux episodes (pH decrease of <4 and MII-detected reflux). For the detection of weakly acidic reflux 40 MII-pH studies were included. Each study initially was read by identifying WAR on the pH tracing. Subsequently, studies were re-analyzed using MII tracings, classifying MII-detected reflux episodes into acid, WAR, or nonacid reflux. For the detection of acid reflux the pH alone compared with MII-pH yielded a specificity of 68%, 67%, and 58%, respectively, for either abnormal percentage time of pH less than 4, positive symptom index, or both. The percentage time that the pH was less than 4 was significantly higher using pH alone compared with MII-pH. Eighty-one percent of acid gastroesophageal reflux episodes exclusively detected by pH were associated with MII-detected swallow. For the detection of WAR compared with MII, pH alone had a sensitivity of only 28%. Eighty-three percent of WAR episodes detected by pH were not associated with MII-detected reflux. The use of pH alone for the detection of acid reflux is very sensitive but lacks specificity compared with MII-pH. pH alone may overdiagnose abnormal acid reflux in up to 22% of tested patients. Also, the use of pH for the detection of WAR has poor sensitivity.

Combined multichannel intraluminal impedance–pH monitoring to select patients with persistent gastro-oesophageal reflux for laparoscopic Nissen fundoplication

Combined multichannel intraluminal impedance-pH (MII-pH) monitoring detects gastro-oesophageal reflux and identifies acid and non-acid reflux events. It can be used in patients with persistent symptoms on proton-pump inhibitor (PPI) therapy. The aim of this study was to assess laparoscopic Nissen fundoplication as a treatment for patients with persistent symptoms associated with reflux despite acid suppression documented by MII-pH monitoring. A prospectively maintained database identified patients with persistent symptoms of gastro-oesophageal reflux disease despite PPI therapy who had undergone MII-pH monitoring and this was cross-referenced with patients who had undergone fundoplication at this institution. Follow-up after fundoplication was by periodic telephone interview and review of clinical records. Of 200 evaluated patients, 19 (14 female; mean age 40 (range 0.7-78) years) underwent laparoscopic Nissen fundoplication. Before surgery, 18 of 19 patients had a positive symptom index (at least half of symptoms associated with reflux) and one, a negative symptom index. After a mean follow-up of 14 (range 7-25) months, 16 of 17 (94 per cent) patients with a positive symptom index were asymptomatic or markedly improved (one patient was lost to follow-up). Persistent symptoms occurred in the patient with a negative symptom index, and one patient had recurrent symptoms after 9 months. Patients with a positive symptom index resistant to PPIs with non-acid or acid reflux demonstrated by MII-pH monitoring can be treated successfully by laparoscopic Nissen fundoplication.

Papel dos testes provocativos esofagianos na investigação de pacientes com dor torácica de origem indeterminada

Traditional methods employed in esophageal investigation of patients with chest pain of undetermined origin includes upper endoscopy, esophageal manometry and pH monitoring. These methods many times disclose abnormalities that can only be enrolled as the possible cause of chest pain. Provocative tests can reproduce pain in the laboratory, establishing its esophageal origin. Determine the positivity of acid perfusion test, edrophonium and balloon distension in patients with chest pain of undetermined origin and compare with results of traditional exams, establishing the gain for the diagnosis of esophageal pain. Forty patients with chest pain of undetermined origin (normal coronary angiography), 80% female, mean age of 54.7 years were submitted to traditional exams and provocative tests. Upper endoscopy disclosed erosive esophagitis in two (5%) and peptic ulcer in one (2.5%), esophageal manometry was abnormal in 60%. pH monitoring was abnormal in 14 (35%) with a positive symptom index in 7. Chest pain was considered of proved esophageal origin by traditional exams in 7 (17.5%) patients with a positive symptom index and of probable esophageal origin in 19 (47.5%) being 8 with gastroesophageal reflux disease and 11 abnormal esophageal motility. In 14 (35%) an esophageal origin could not be demonstrated. The acid perfusion test was positive in 10 (25%), edrophonium test in 8 (20%) and balloon distension test in 15 (37.5%) and at least one provocative test was positive in 23 (57.5%) patients. The introduction of provocative tests allowed the diagnosis of proved esophageal pain in 12 of 19 (63.1%) patients with probable esophageal pain and in 6 of 14 (42.8%) with normal or inconclusive traditional exams what represented a diagnostic gain of 45% (18/40). Two patients had negative provocative tests and a positive symptom index, making a total of 25 (62.5%) patients with proved esophageal pain.