Use of a positional therapy device significantly improves nocturnal gastroesophageal reflux symptoms.

The aim of this study was to measure the efficacy of a positional therapy device (PTD) at reducing proton pump inhibitor (PPI) refractory nocturnal GERD symptoms. Among patients with GERD, nocturnal symptoms are very common. A recent study demonstrated a decrease in nocturnal acid exposure and reflux episodes in healthy volunteers who slept using a PTD. This is a single-center prospective trial involving patients on anti-secretory medications with continued nocturnal heartburn and regurgitation. Patients completed the Nocturnal GERD Symptom Severity and Impact Questionnaire (N-GSSIQ) and GERD health-related quality of life questionnaire (GERD-HRQL) at enrollment. Patients were instructed to sleep on the PTD for at least 6 hours a night during the two week study period; subjects continued their baseline anti-secretory medication dose. After 2 weeks, the questionnaires were repeated. A total of 27 patients (16 females and 11 males; age 57.8 ± 15.1) were recruited. After 2 weeks of PTD use, N-GSSIQ scores significantly improved from baseline, with a mean total score improvement of 39.5 (mean 57.7 [pre] vs. 18.2 [post], P < 0.001). Significant improvement from baseline was also observed for the GERD-HRQL questionnaire (29.8 vs. 16.7, P < 0.001). No adverse events were reported. At 3 months after the trial period, 91% of the subjects continued to use the PTD on a nightly basis. Use of the PTD significantly decreased nocturnal GERD symptoms and improved GERD-HRQL. The PTD was well tolerated during the study period and for 3 months after enrollment.

Timed barium esophagram in achalasia types.

Relationships of timed barium esophagram (TBE) findings to achalasia types defined by high-resolution manometry (HRM) have not been elucidated. Therefore, we correlated preoperative TBE and HRM measurements in achalasia types and related these to patient symptoms and prior treatments. From 2006 to 2013, 248 achalasia patients underwent TBE and HRM before Heller myotomy. TBE height and width were recorded at 1 and 5 minutes; HRM measured lower esophageal sphincter mean basal pressure, integrated relaxation pressure (IRP), and mean esophageal body contraction amplitude. Achalasia was classified into types I (25%), II (65%), and III (9.7%). TBE height at 5 minutes was higher for I (median 8 cm; interquartile range 6-12) and II (8 cm; 8-11) than for III (1 cm; 0-7). TBE width at 5 minutes was widest (3 cm; 2-4), narrower in II (2 cm; 2-3), and narrowest in I (1 cm; 0-2), P < 0.001. Volume remaining at 1 and 5 minutes was lower in III (1 m(2) ; 0-16) than I (42 m(2) ; 17-106) and II (39 m(2) ; 15-60), highlighting poorer emptying of I and II. Increasing TBE width correlated with deteriorating morphology and function from III to II to I. Symptoms poorly correlated with TBE and HRM. Prior treatment was associated with less regurgitation, faster emptying, and lower IRP. Although TBE and HRM are correlated in many respects, the wide range of their measurements observed in this study reveals a spectrum of morphology and dysfunction in achalasia that is best characterized by the combination of these studies.

Acute pancreatitis: a prospective study of its incidence, aetiology, severity, and mortality in Iceland.

OBJECTIVE: To evaluate the incidence, aetiology, severity and mortality of patients with acute pancreatitis. DESIGN: Prospective study. SETTING: University hospital, Iceland. PATIENTS AND METHODS: All 50 patients diagnosed with acute pancreatitis during the one-year period October 1998-September 1999 inclusive. MAIN OUTCOME MEASURES: APACHE II, and Ranson and Imrie scores, and C-reactive protein (CRP) concentrations. The Balthazar-Ranson criteria were used for scoring of computed tomograms (CT). RESULTS: 27 of the 50 patients were male. The median age of the whole series was 60 years (range 19-85). The estimated incidence was 32/100000 for the first attack of acute pancreatitis. The causes were; gallstones 21 (42%), alcohol 16 (32%), miscellaneous 12 (24%), and idiopathic 1 (2%). 15 (33%) of the patients had APACHE II scores > or = 9, 17 (38%) had Ranson scores of > or = 3, 23 (50%) had Imrie scores of > or = 3, and 16 (34%) had CRP concentrations over 210 mg/L during the first 4 days or > 120 mg/L during the first week. Seven patients had severe pancreatitis. 2 patients in the whole group died, and both had clinically severe pancreatitis. CONCLUSIONS: This study indicates that the incidence of less severe acute pancreatitis is rising. Prospective assessment makes it possible to evaluate the aetiological factors more accurately. Measurement of the CRP concentration is an attractive and simple alternative to the severity scoring systems currently in use.

Botulinum toxin versus pneumatic dilatation in the treatment of achalasia: a randomised trial.

BACKGROUND: Intrasphincteric injection of botulinum toxin is a new treatment option for achalasia. AIMS: To compare the immediate and long term efficacy of botulinum toxin with that of pneumatic dilatation. METHODS: Symptomatic patients with achalasia were randomised to botulinum toxin (22 patients, median age 57 years) or pneumatic dilatation (20 patients, median age 56 years). Symptom scores were assessed initially, and at one, three, six, nine, and 12 months after treatment. Objective assessment included oesophageal manometry initially and at one month, and barium oesophagram initially and at one, six, and 12 months post-treatment. RESULTS: Pneumatic dilatation resulted in a significantly (p=0.02) higher cumulative remission rate. At 12 months, 14/20 (70%) pneumatic dilatation and 7/22 (32%) botulinum toxin treated patients were in symptomatic remission (p=0.017). Failure rates were similar initially, but failure over time was significantly (p=0.01) higher after botulinum toxin (50%) than pneumatic dilatation (7%). Pneumatic dilatation resulted in significant (p<0.001) reduction in symptom scores, and lower oesophageal sphincter pressure, oesophageal barium column height, and oesophageal diameter. Botulinum toxin produced significant reduction in symptom scores (p<0.001), but no reduction in objective parameters. CONCLUSIONS: At one year pneumatic dilatation is more effective than botulinum toxin. Symptom improvement parallels objective oesophageal measurements after pneumatic dilatation but not after botulinum toxin treatment for achalasia.

Somatostatin or octreotide compared with H2 antagonists and placebo in the management of acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis.

PURPOSE: To determine the efficacy of somatostatin or octreotide for the treatment of acute nonvariceal upper gastrointestinal hemorrhage. DATA SOURCE: Database searches of English-language articles published between 1966 and 1996 and the bibliographies of all related articles and textbook chapters. STUDY SELECTION: Randomized clinical trials comparing somatostatin or octreotide with H2 blockers or placebo in patients with a clinical or endoscopic diagnosis of acute nonvariceal upper gastrointestinal hemorrhage. DATA EXTRACTION: Methods and quality of the studies were evaluated, and quantitative data on outcomes, including continued bleeding, rebleeding during the treatment period, need for surgery, and transfusion requirement, were extracted. DATA SYNTHESIS: Among 1829 patients from 14 trials, the relative risk (RR) for continued bleeding or rebleeding was 0.53 (95% CI, 0.43 to 0.63) in favor or somatostatin, with a number needed to treat (NNT) of 5. Among 7 investigator-blinded trials, the relative risk was 0.73 (CI, 0.64 to 0.81) and the NNT was 11. Somatostatin was efficacious for peptic ulcer bleeding (RR, 0.48 [CI, 0.39 to 0.59]; NNT, 4) and showed a trend toward efficacy for non-peptic ulcer bleeding (RR, 0.62 [CI, 0.39 to 1.002]). Although the overall results suggested a decreased need for surgery in the somatostatin group, a subgroup analysis of investigator-blinded trials revealed a more modest effect that was not statistically significant (RR, 0.94 [CI, 0.87 to 1.001]). CONCLUSION: Somatostatin may reduce the risk for continued bleeding from acutely bleeding peptic ulcer disease. Somatostatin may be useful either as an adjunct treatment before endoscopy or when endoscopy is unsuccessful, contraindicated, or unavailable.

Timed barium swallow: a simple technique for evaluating esophageal emptying in patients with achalasia.

OBJECTIVE: Our purpose was to define a simple technique for timing a barium swallow by which radiologists can assess esophageal emptying in patients with achalasia before and after minimally invasive therapy. Our purpose was also to determine the best method of quantifying the degree of emptying using this timed technique. MATERIALS AND METHODS: In the barium swallow technique, upright frontal spot films of the esophagus are obtained at 1, 2, and 5 min after ingestion of 100-200 ml of low-density (45% weight in volume) barium sulfate (volume of barium determined by patient tolerance). Forty-two of these barium swallows done by 23 patients with achalasia were retrospectively reviewed. The examination served either as a baseline study or as a 1-month follow-up study after patients had undergone pneumatic dilatation or Clostridium botulinum toxin injection. The spot films were digitized, and a region of interest was drawn around the column of barium by two observers. The change in area seen in the region of interest on the 1- and 5-min films served as the gold standard for percentage of emptying. The spot films were then analyzed by four other observers, each of whom independently, subjectively, and qualitatively estimated the percentage of emptying between the 1- and 5-min spot films. Percentages were divided into quintiles. On a separate occasion, each of these four observers also independently measured the height and width of the barium column on the 1- and 5-min spot films. The product of height times width seen on the 1- and 5-min films became the quantitative estimate for percentage of emptying. RESULTS: We found no statistically significant difference between the percentage of emptying as measured on the digitized images by the two observers and the height-times-width calculations or qualitative emptying percentage as estimated by the four observers. Interobserver agreement for the area evaluated on the digitized films as well as the height-times-width measurements and qualitative estimates of emptying was almost perfect (the correlation coefficients being 0.99, 0.87, and 0.93, respectively). CONCLUSION: The timed barium swallow is a simple and reproducible technique. Both qualitative assessment and estimated change in area based on height-times-width measurements of the barium column are accurate methods of estimating esophageal emptying.

Surveillance of patients with Barrett's esophagus for dysplasia and cancer with balloon cytology.

BACKGROUND & AIMS: A less costly cancer surveillance method for Barrett's esophagus is desirable. The aim of this study was to compare nonendoscopic balloon cytology with biopsy and brush cytology for detecting dysplasia and carcinoma in patients with Barrett's esophagus. METHODS: Patients in a surveillance program underwent balloon cytology before endoscopy with biopsy and brush cytology. Results of cytology were compared with those of histology. RESULTS: Adequate columnar epithelium was obtained in 52 of 63 (83%) patients with balloon cytology and 59 of 61 (97%) with brush cytology. Balloon cytology obtained abnormal cells in 6 of 8 patients with adenocarcinoma, 2 of 2 patients with high-grade dysplasia, and 2 of 8 patients with low-grade dysplasia. Sensitivity of balloon cytology for high-grade dysplasia or carcinoma was 80% but only 25% for low-grade dysplasia. No patients without dysplasia or carcinoma had abnormal cells. Brush cytology was abnormal in all 11 patients with high-grade dysplasia or carcinoma but only 2 of 9 patients with low-grade dysplasia (sensitivity, 22%). Two of 39 patients without dysplasia had abnormal cells (specificity, 95%). Balloon cytology cost was sixfold less than endoscopy with biopsy. CONCLUSIONS: Balloon cytology detected 80% of patients with high-grade dysplasia or carcinoma when sampling was adequate. Brush cytology data suggest that a more abrasive balloon may improve balloon cytology sensitivity. The potential cost savings of balloon cytology compared with endoscopic cancer surveillance in Barrett's esophagus support further studies of this technique.

The lack of association between adenocarcinoma of the esophagus and gastric surgery: a retrospective study.

BACKGROUND: The cause of the rapid increase in the incidence of adenocarcinoma of the esophagus since the 1970s is unknown. OBJECTIVE: To test the hypothesis that duodenogastroesophageal reflux causes adenocarcinoma of the esophagus by comparing the frequency of gastric surgery (a human model of duodenogastroesophageal reflux) and other potential risk factors between patients with adenocarcinoma and patients with squamous cell carcinoma of the esophagus. METHODS: Medical records of all patients with adenocarcinoma or squamous cell carcinoma of the esophagus seen at the Cleveland Clinic Foundation between 1987 and 1994 were reviewed. The following data were retrieved: age, gender, race, tumor location, history of gastric surgery and gastroesophageal reflux symptoms, and use of tobacco, alcohol, histamine-2 receptor antagonists, and proton pump inhibitors. RESULTS: The data of 325 patients with adenocarcinoma (73.5%) and 117 patients with squamous cell carcinoma (26.5%) were analyzed. No differences were found between the groups in age, proportion with gastric surgery (patients with adenocarcinoma: 1.2%, 95% confidence interval 0.3-3.1%; patients with squamous cell carcinoma: 0.9%, 95% confidence interval 0.0-4.7%), smoking (76.7 vs 81.6%), or alcohol use (71.8 vs 79.1%). Significant risk factors associated with adenocarcinoma of the esophagus were male gender, white race, distal cancer location, and Barrett's esophagus. CONCLUSIONS: Previous gastric surgery is rarely found in patients with esophageal cancer and is performed with equal frequency in patients with adenocarcinoma and those with squamous cell carcinoma of the esophagus. This suggests that gastric surgery and its associated duodenogastroesophageal reflux do not play a role in the etiology and rising incidence of adenocarcinoma of the esophagus. White males in their mid-60s with Barrett's esophagus who smoke and drink alcohol are at highest risk for adenocarcinoma of the esophagus.

Achalasia is not associated with measles or known herpes and human papilloma viruses.

Achalasia is an esophageal motility disorder of unknown etiology. Several studies suggest possible herpes or measles virus etiology, but results are inconclusive. The aim of this study was to test whether herpesvirus (HV), measles (MV), or human papilloma virus (HPV) sequences could be detected in myotomy specimens from a wide spectrum of achalasia patients, using the polymerase chain reaction (PCR) technique. Myotomy specimens from 13 achalasia patients, esophagectomy specimens from nine esophageal cancer patients, and autopsy specimens from six fetuses were studied with the PCR technique. Paired oligonucleotide primers of HV (HSV-1 and 2, CMV, EBV, VZV, and HHV-6), MV and HPV sequences and exon 3 of the HPRT gene were used for the PCR DNA amplification. Amplified products were resolved on agarose gels and stained with ethidium bromide. All specimens yielded the appropriate-sized products for exon 3 of the HPRT and viral controls. No amplified products were seen in the achalasia specimens or controls corresponding to any of the virus sequences tested. The absence of HV, MV, and HPV sequences suggests that these viruses are not associated with achalasia but does not exclude the possibility of a previously unidentified virus as a causal agent. Further studies aimed at identifying an unknown viral agent as a cause for achalasia are warranted.

Achalasia: what's new in diagnosis and treatment?

Achalasia is an esophageal motility disorder of unknown cause, characterized clinically by dysphagia and regurgitation and diagnosed by manometry and/or barium esophagogram. Good long-term symptomatic relief can be achieved with pneumatic dilatation and myotomy. Botulinum toxin injection and videoendoscopic surgery are being evaluated as less invasive forms of therapy.

Animal models of hepatic encephalopathy and hyperammonemia.

Animal models of chronic liver disease with hyperammonemia are currently available to investigators. Two in particular have been utilized extensively. Carbon tetrachloride induced (CCl4) cirrhosis in the rat and portacaval shunt in the same species and other animals particularly the dog. In regards to hepatic encephalopathy, however, the CCl4 cirrhosis rat model seems to display few behavioral changes unless very advanced decompensated cirrhosis is produced. Further work should be done on this model to verify the development of encephalopathy and to improve reproducibility. The portacaval shunt rat on the other hand clearly has a consistent albeit subtle set of behavioral changes. Recent improvements in detecting these changes and more importantly showing reversal or improvement by neomycin or a low protein diet are a major advance. Hopefully, more laboratories will be able to reproduce this reversible change in behavior. Experiences gained from 7 years of using the portacaval shunt rat and other models of liver disease are described.

Tumours in Iceland. 15. Ependymoma. A clinicopathological and immunohistological study.

Thirteen ependymomas reported to the Icelandic Cancer Registry during a 32-year period (1955-1986) were histologically reviewed and reclassified according to the WHO Histological Typing of Tumours of the Central Nervous System. The annual incidence rate of ependymoma was 0.20/100.000. Clinical observations and data on biological behaviour and immunohistochemistry are presented. Four tumours were supratentorial, six infratentorial and three intraspinal. There were ten males and three females with a mean age of 32 years (range 2.5-68). The mean postoperative survival of nine surgically treated patients was 35.5 months. Histologically, eight tumours were classical ependymomas, three anaplastic and two myxopapillary. Of 11 tumours stained for GFAP, nine were positive. Nine of 10 tumours tested were positive for vimentin, five for NSE and four for S-100. None of the 10 tumours showed reactivity with AFP, CEA, chromogranin, desmin, factor VIII, keratin or neurofilament.