Canadian Consensus Conference on the management of gastroesophageal reflux disease in adults - update 2004.

BACKGROUND: Gastroesophageal reflux disease (GERD) is the most prevalent acid-related disorder in Canada and is associated with significant impairment of health-related quality of life. Since the last Canadian Consensus Conference in 1996, GERD management has evolved substantially. OBJECTIVE: To develop up-to-date evidence-based recommendations relevant to the needs of Canadian health care providers for the management of the esophageal manifestations of GERD. CONSENSUS PROCESS: A multidisciplinary group of 23 voting participants developed recommendation statements using a Delphi approach; after presentation of relevant data at the meeting, the quality of the evidence, strength of recommendation and level of consensus were graded by participants according to accepted principles. OUTCOMES: GERD applies to individuals who reflux gastric contents into the esophagus causing symptoms sufficient to reduce quality of life, injury or both; endoscopy-negative reflux disease applies to individuals who have GERD and a normal endoscopy. Uninvestigated heartburn-dominant dyspepsia - characterised by heartburn or acid regurgitation - includes erosive esophagitis or endoscopy-negative reflux disease, and may be treated empirically as GERD without further investigation provided there are no alarm features. Lifestyle modifications are ineffective for frequent or severe GERD symptoms; over-the-counter antacids or histamine H2-receptor antagonists are effective for some patients with mild or infrequent GERD symptoms. Proton pump inhibitors are more effective for healing and symptom relief than histamine H2-receptor antagonists; their efficacy is proportional to their ability to reduce intragastric acidity. Response to initial therapy - a once-daily proton pump inhibitor unless symptoms are mild and infrequent (fewer than three times per week) - should be assessed at four to eight weeks. Maintenance medical therapy should be at the lowest dose and frequency necessary to maintain symptom relief; antireflux surgery is an alternative for a small proportion of selected patients. Routine testing for Helicobacter pylori infection is unnecessary before starting GERD therapy. GERD is associated with Barrett's epithelium and esophageal adenocarcinoma but the risk of malignancy is very low. Endoscopic screening for Barrett's epithelium may be considered in adults with GERD symptoms for more than 10 years; Barrett's epithelium and low-grade dysplasia generally warrant surveillance; endoscopic or surgical management should be considered for confirmed high-grade dysplasia or malignancy. CONCLUSION: Prospective studies are needed to investigate clinically relevant risk factors for the development of GERD and its complications; GERD progression, on and off therapy; optimal management strategies for typical GERD symptoms in primary care patients; and optimal management strategies for atypical GERD symptoms, Barrett's epithelium and esophageal adenocarcinoma.     

Relationship between neutrophil elastase and acute lung injury in humans

We conducted clinical trials in patients with acute lung injury (ALI) associated with systemic inflammatory response syndrome using a selective neutrophil elastase inhibitor, sivelestat sodium hydrate (Sivelestat), to investigate the involvement of neutrophil elastase in ALI. In the phase III double-blind study (Study 1) in 230 patients, the efficacy of Sivelestat was evaluated with the pulmonary function improvement (PFI) rating as the primary endpoint, and the weaning rate from mechanical ventilator, the discharge rate from intensive care unit (ICU), and the survival rate as secondary endpoints. Afterwards, an unblinded study (Study 2) in 20 patients was conducted using procedures for weaning from mechanical ventilation to reevaluate its efficacy with ventilator-free days (VFD) value, the primary endpoint, and to compare with that of Study 1 subgroup, which met the selection criteria used in Study 2. Sivelestat increased PFI rating, reduced duration of mechanical ventilation, and shortened stay in ICU in Study 1, although there was no significant efficacy on the survival rate. VFD value in Study 2 was comparable to that in the optimal-dose group of Study 1 subgroup, and increase in VFD value correlated with PFI rating and increase in ICU free days. It was concluded that neutrophil elastase may be involved in the pathogenesis of ALI in humans.     

A randomized trial comparing omeprazole, ranitidine, cisapride, or placebo in helicobacter pylori negative, primary care patients with dyspepsia: the CADET-HN Study

BACKGROUND: The management of Helicobacter pylori negative patients with dyspepsia in primary care has not been studied in placebo-controlled studies. METHODS: H. pylori negative patients with dyspepsia symptoms of at least moderate severity (> or =4 on a seven-point Likert scale) were recruited from 35 centers. Patients were randomized to a 4-wk treatment of omeprazole 20 mg od, ranitidine 150 mg bid, cisapride 20 mg bid, or placebo, followed by on-demand therapy for an additional 5 months. Treatment success was defined as no or minimal symptoms (score < or = 2 out of 7), and was assessed after 4 wk and at 6 months. RESULTS: Five hundred and twelve patients were randomized and included in the intention-to-treat (ITT) analysis. At 4 wk, success rates (95% CI) were: omeprazole 51% (69/135; 43-60%), ranitidine 36% (50/139, 28-44%), cisapride 31% (32/105, 22-39%), and placebo 23% (31/133, 16-31%). Omeprazole was significantly better than all other treatments (p < 0.05). The proportion of patients who were responders at 4 wk and at 6 months was significantly greater for those receiving omeprazole 31% (42/135, 23-39%) compared with cisapride 13% (14/105, 7-20%), and placebo 14% (18/133, 8-20%) (p= 0.001), but not ranitidine 21% (29/139, 14-27%) (p= 0.053). The mean number of on-demand study tablets consumed and rescue antacid used was comparable across groups. Economic analysis showed a trade-off between superior efficacy and increased cost between omeprazole and ranitidine. CONCLUSION: Treatment with omeprazole provides superior symptom relief compared to ranitidine, cisapride, and placebo in the treatment of H. pylori negative primary care dyspepsia patients.     

Combined semi-nested polymerase chain reaction and heteroduplex analysis for detecting monoclonality of IgH rearrangement in patients with follicular lymphoma

A new, sensitive method combining seminested polymerase chain reaction (PCR) and heteroduplex analysis was used to detect follicular lymphoma (FL) cells in peripheral blood. Based on the detection of IgH rearrangement in DNA from peripheral blood leukocytes, the method demonstrated the presence of monoclonal B cells in FL patients with high frequency.     

Hepatic resection under in situ hypothermic hepatic perfusion

BACKGROUND/AIMS: Temporary inflow occlusion of the portal triad has been used frequently in hepatectomy to minimize bleeding. On the other hand, Pringle's maneuver produces ischemic-reperfusion injury especially in patients with underlying liver disease. METHODOLOGY: Thirty-seven cases of hepatic resections were performed with intermittent Pringle's maneuver (IP group; n = 17) and in situ hypothermic perfusion (CP group; n = 20). In the CP group, hepatic inflow was continuously occluded, and 4-degree Centigrade Ringer's lactate was administered by drip during resection. Hepatic outflow occlusion was not performed. RESULTS: All patients tolerated the procedures well. Cold perfusion technique significantly decreased both the times required and the blood loss in hepatectomy (p < 0.05). Serum hyaluronic acid levels gradually increased after the induction of hepatectomy and peaked 10 minutes after reperfusion in the both groups. Thereafter, it decreased and showed a significantly lower level in the CP group until 60 minutes after reperfusion (p < 0.05). Hepaplastin levels remained significantly higher in the CP group one week after operation (p < 0.05). CONCLUSIONS: Using the technique of in situ hypothermic perfusion, we can prolong the ischemic time safely with minimal systemic influence even in cases with underlying liver diseases. This may compare favorably with intermittent Pringle's maneuver in terms of reducing hepatic sinusoidal endothelial cell damage during hepatectomy and reperfusion.     

Evaluation of salvaged myocardium after acute myocardial infarction using single photon emission computed tomography after 201Tl-glucose-insulin infusion.

BACKGROUND: GIK-201Tl imaging reportedly improves the detection of viable myocardium, so the present study evaluated whether it can detect myocardial viability after acute myocardial infarction (AMI). METHODS AND RESULTS: Resting 201Tl and 99mTc-pyrophosphate (PYP) dual single photon emission computed tomography (SPECT) and 201Tl SPECT after 201Tl with GIK (10% glucose, insulin 5 U, and KCl 10 mmol) infusion (GIK-201Tl) were performed in 25 AMI patients within 10 days of admission. GIK-201Tl SPECT images were obtained immediately and 4 h after infusion. Left ventriculography (LVG) was performed within 3 weeks and at 6 months when follow-up 201Tl SPECT was also performed. From 20 SPECT segments, both the summed defect score (RDS) and the number of defect segments (ES) were calculated. The infarcted area was defined as 99mTc-PYP uptake segments. Wall motion was estimated in 7 LVG segments. The ES of R-201Tl (5.5 +/- 2.8), immediate GIK-201Tl (4.0 +/- 2.3), and 4-h GIK-201Tl (5.6 +/- 2.7) were lower than that of 99mTc-PYP (7.5 +/- 4.1) (p<0.05), and the ES had significantly declined 6 months later on 201Tl (3.5 +/- 2.8) (p<0.05). Although the RDS of R-201Tl (11.3 +/- 7.9) and 4-h GIK-201Tl (11.2 +/- 6.3) were greater than at the 6-month 201Tl (7.1 +/- 6.5), immediate GIK-201Tl (7.4 +/- 6.5) was equivalent to follow-up 201Tl. The sensitivity of immediate GIK-201Tl was highest among the imaging methods. CONCLUSION: To detect myocardial viability after AMI, early imaging with GIK-201Tl is more useful than resting 201Tl imaging.     

Right atrial abnormalities in a patient with arrhythmogenic right ventricular cardiomyopathy without ventricular tachycardia

We describe a 59-year-old woman with sick sinus syndrome (SSS) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Diagnosis of SSS was made because she had frequent episodes of sinus arrest with prolonged ventricular asystole. Cardiac images showed a dilated right atrium (RA) and a right ventricle (RV). Electroanatomical mapping of the RA showed extensive scarring with no recordable electrical potentials. Although she had frequent premature ventricular contractions, neither spontaneous ventricular tachycardia (VT) nor induced VT was observed. Microscopic examination of the RV indicated fibrofatty myocardium. Atrial arrhythmias associated with SSS may be the cause of symptoms in some cases of ARVC.     

Detection of BCL2-IGH rearrangement on paraffin-embedded tissue sections obtained from a small submucosal tumor of the rectum in a patient with recurrent follicular lymphoma

A 59-year-old woman was admitted to our hospital because of recurrent follicular lymphorna (FL). Colonoscopic examination revealed a rectal submucosal tumor (SMT) without any erosions and ulcers. In this patient, it was difficult to distinguish non-Hodgkin‘s lymphoma (NHL) invasion from other disorders of the colon including carcinoid tumor merely based on endoscopic findings. Histopathologic and immunohistochemical studies on biopsy specimens showed an infiltration of atypical lymphocytes that were positive for CD20 and BCL2 but negative for UCHL-1. Fluorescence in situ hybridization on paraffin-embedded tissue sections (T-FISH) identified a translocation of BCL2 with IGHgene.Based on these findings, the tumor was defined as an invasion of FL. T-FISH method is useful for the detection of a monoclonality of atypical lymphocytes in an SMT of the gastrointestinal tract, and particularly for the detection of chromosomal translocations specific to lymphoma subtypes.     

Liver metastasis of rectal cancer with intraluminal growth in the extrahepatic bile duct

Metastatic liver tumors are considered to have a tendency for expansive growth and rarely invade the bile duct. We recently encountered a resected case of liver metastasis from rectal cancer with intraluminal growth in the extrahepatic bile duct with a successful left trisegmentectomy of the liver. A 54-year-old woman underwent a posterior total pelvic exenteration for advanced rectal cancer. Ultrasonography and computed tomography four months after the first operation demonstrated a solitary occupied lesion in the liver with dilation of the left hepatic duct. Endoscopic retrograde cholangiopancreatography disclosed a filling defect in the intra- to extrahepatic bile duct. Liver metastasis from rectal cancer with intraluminal growth in the bile duct was suspected despite a consideration of primary bile duct cancer. A left trisegmentectomy of the liver and resection of the extrahepatic bile duct with a right hepatojejunostomy were performed. The tumor had invaded the intrahepatic bile duct and had developed intraluminally in the extrahepatic bile duct. Tumor thrombi were microscopically found in the bile duct of the left caudal lobe. Liver metastasis arising from colorectal cancer with intraluminal growth in the bile duct is rare, however we encountered such a case with a successful resection involving a left trisegmentectomy of the liver.