bluuebunny/crossref_metadata_2025 huggingface dataset:
Friedmann inflation in Horava–Lifshitz gravity with a scalar field
Authors: Tawfik Abdel Nasser , Diab Abdel Magied , El Dahab Eiman Abou
Published: March 2016

We study Friedmann inflation in general Horava–Lifshitz (HL) gravity with detailed and nondetailed and also without the projectability conditions. Accordingly, we derive the modifications in the Friedmann equations due to single scalar field potentials describing power-law and minimal-supersymmetrically extended inflation. By implementing four types of the equations-of-state characterizing the cosmic background geometry, the dependence of the tensorial and spectral density fluctuations and their ratio on the inflation field is determined. The latter characterizes the time evolution of the inflation field relative to the Hubble parameter. Furthermore, the ratio of tensorial-to-spectral density fluctuations is calculated in dependence on the spectral index. The resulting slow-roll parameters apparently differ from the ones deduced from the standard General Relativity (Friedmann gravity). We also observe that the tensorial-to-spectral density fluctuations continuously decrease when moving from nondetailed HL gravity, to Friedmann gravity, to HL gravity without the projectability, and to detailed HL gravity. This regular pattern is valid for three types of cosmic equations-of-state and different inflation potential models. The results fit well with the recent Planck observations.
Cancer of the Pancreas: The Best Image for Early Detection – CT, MRI, PET or US?
Authors: Hanbidge Anthony E
Published: March 2016

Pancreatic cancer has a poor prognosis, and the best chance for survival is to diagnose the tumour at an early stage. Abdominal ultrasound, computed tomography, magnetic resonance imaging and endoscopic retrograde cholangiopancreatography are the most commonly used radiological techniques for imaging the pancreas. The diagnostic evaluation should be tailored to the individual patient. Dual-phase helical computed tomography and magnetic resonance imaging have similar accuracies for detecting and staging pancreatic adenocarcinoma. Sonography results are highly dependent on the skill and persistence of the operator. No radiological examination is very sensitive at visualizing small metastases in the lymph nodes and peritoneum, or on the surface of the liver. Thus, it is difficult to establish with certainty whether a tumour is resectable. Another major challenge is to differentiate cancer from an inflammatory mass in chronic pancreatitis. Functional imaging (using positron emission tomography with fluorodeoxyglucose) may be helpful, especially if the images are fused with those of computed tomography or magnetic resonance imaging. The diagnostic accuracies, applications and limitations of the various modalities are discussed.
Tabulation of Myeloid, Lymphoid and Intestinal Malignancies in Crohn’s Disease
Authors: Freeman Hugh J
Published: March 2016

A variety of malignant complications occur in Crohn’s disease, and previous studies have recorded an increased intestinal cancer risk. The present investigation tabulated myeloid and lymphoid malignancies compared with intestinal cancers in 1000 consecutively evaluated patients with Crohn’s disease who were followed over an extended period by a single clinician. Myeloid and lymphoid neoplasms were present in 0.5% of patients, while cancer in the intestinal tract was detected in 1%. Most of these patients with a malignancy had Crohn’s disease for a prolonged period of more than 20 years and had negative outcomes, including death or presentations with advanced disease. In this cohort, lymphoma was not detected in a single patient after definition of Crohn’s disease, possibly reflecting the limited use of immunosuppressives or infused biological agents in this clinical practice. Bypassed rectal ‘stumps’ were associated with subsequent colorectal cancer in half of all males with colon cancer in this series, suggesting an important risk factor following colectomy in Crohn’s disease. Epithelial dysplasia was detected in only a single male patient before colorectal cancer, implying that this histopathological marker may be a poor predictor of subsequent colon cancer development in Crohn’s disease, an inflammatory bowel disease process that is typically patchy or focal in distribution in the intestinal tract.
Risks and Benefits ofHelicobacter pyloriEradication: Current Status
Authors: Hunt Richard H , Fallone Carlo , van Zanten Sander Veldhuyzen , Sherman Phil , Smaill Fiona , Thomson Alan BR , the Canadian Helicobacter Study Group
Published: March 2016

In patients with diseases known to be associated withHelicobacter pyloriinfection, such as peptic ulcer, treatment of the underlying infection is the standard of care. However, in most major consensus management guidelines, including those published in Canada, widespread testing forH pyloriinfection is not recommended. This practice is not encouraged because of insufficient evidence of cost-benefit in gastric cancer prevention, the potential for increases in antibiotic resistance and the controversial hypothesis of potential negative effects of eradication in certain clinical entities. For example, there is insufficient evidence to recommend against eradicatingH pyloridiscovered in a patient with symptoms of gastroesophageal reflux disease. The management guidelines designed specifically in Canada should, therefore, continue to be applied, withH pyloridiagnosed and treated in appropriately selected patients.
Giant Liposarcoma of the Esophagus
Authors: Beaudoin Annie , Journet Charles , Watier Alain , Mongeau Charles-Jacques , Chagnon Michel , Beaudry René
Published: March 2016

Liposarcomas of the gastrointestinal tract are exceedingly rare. Only nine cases of esophageal involvement have been described. A 68-year-old woman presented with an episode of vomiting followed by extrusion of a polypoid mass from the mouth. This 10th case of esophageal liposarcoma is the first in the literature to report a recurrence 25 years after the first episode.
Clinical Experience with Infliximab for Crohn’s Disease: The First 100 Patients in Edmonton, Alberta
Authors: Sample Clifford , Bailey Robert J , Todoruk Dennis , Sadowski Daniel , Leah Gramlich , Milan Mario , Cherry Raeleen , Ma Mang , Lalor Eoin , McKaigney John , Sherbaniuk Richard , Matic Kata , Switzer Connie , Richard N Fedorak
Published: March 2016

OBJECTIVE: To determine whether the clinical efficacy and safety of infliximab in diverse clinical referral practices was similar to that seen in the randomized, controlled clinical trials.

METHODS: Data were gathered from a review of charts of 109 consecutive patients with inflammatory and/or fistulizing Crohn’s disease who received infliximab infusions. Responses were recorded based on the physician’s global clinical assessment and classified as complete, partial or nonresponse.

RESULTS: One hundred nine patients were treated with one to nine infusions of infliximab at a dose of 5 mg/kg and followed up for a median of 24 weeks (range one to 40 weeks). Fifty-four patients were treated for inflammatory disease, 38 for fistulizing disease and 17 for both. Clinical response occurred in 73% (17% complete response, 55% partial response). The clinical response rate did not vary relative to patient demographics, disease distribution, indication for infliximab, or the concomitant use of corticosteroids or immune modifiers. For those taking concomitant immune modifiers, the response rate was 75%. The median time to response was two weeks (range one to six weeks). The median duration of response was 12 weeks (range six to 88 weeks). Reduction or cessation of steroids was possible in 17 of 32 patients. Adverse events related to infliximab occurred in 7% of patients. These events were characterized as mild and did not require stoppage of infliximab therapy, except in one patient who had a treatable anaphylactic-like infusion reaction.

CONCLUSIONS: The patient group in the present study realized significant clinical benefit, with minimal adverse effects, following treatment with infliximab. Clinical response rates paralleled those previously described in placebo controlled trials and retrospective clinical practice reviews. Nevertheless, the complete response rate (ie, remission) in this patient group was lower than that previously described.
Motion – All Patients with GERD Should Be Offered Once in a Lifetime Endoscopy: Arguments against the Motion
Authors: Freston James W
Published: March 2016

The evidence for the recommendation that patients with gastroesophageal reflux disease (GERD) be offered once in a lifetime endoscopy is weak and is not supported by any clinical trials. GERD is a very prevalent condition, yet only 10% of patients with GERD have Barrett’s esophagus (BE). Esophageal adenocarcinoma (EAC) is a rare condition and is uncommon even among patients with BE. A decision analysis found that surveillance of BE patients is performed because of inflated estimates of the rate of progression from BE to EAC. Dysplasia more often regresses to more benign histological findings than to cancer, and transient dysplasia can also lead to a high rate of unnecessary endoscopy. Even though practice guidelines about endoscopic surveillance have been published, there is no consensus among gastroenterologists about appropriate protocols, and many physicians are more aggressive than the guidelines. It has not been proved that surveillance saves lives, in part because BE rarely leads to death from EAC. The favourable results from some specialized centres may not be widely applicable. The recommendation for ‘once in a lifetime’ endoscopy for GERD patients is premature.
Funding the New Biologics – What Can We Learn from Infliximab? The CCOHTA Report: A Gastroenterologist’s Viewpoint
Authors: Hilsden Robert
Published: March 2016

The treatment of severe Crohn’s disease is difficult, and approximately 20% of patients do not respond to conventional therapy, including corticosteroids and immunosuppressives. Infliximab is one of the only treatments of proven efficacy in this group. Awareness of its benefits and risks is incomplete, because the drug has only recently been introduced and published research data are relatively sparse. Economic analyses help to evaluate the value of interventions that are both effective and expensive, but their validity is compromised by input data that involve questionable assumptions. They should not, therefore, be the only basis for funding decisions. Patients with severe Crohn’s disease are frequently unable to be gainfully employed and thus incur significant indirect costs. In a recent study by the Canadian Coordinating Office for Health Technology Assessment (CCOHTA), infliximab was deemed to not meet commonly accepted standards of cost effectiveness. This economic analysis did not incorporate indirect costs, and thus was inherently flawed and likely underestimated infliximab’s value. The CCOHTA report also used population data from a period of time during which treatment of Crohn’s disease was undergoing major transition. The study population was based in Minnesota and thus might not be applicable to Canada. Although they are routinely used in cost effectiveness models, quality-adjusted life-years gained are difficult to translate into practice, and the health care resources required to induce remission (or some other clinically meaningful result) might be a preferable measure. The CCOHTA report also did not include concomitant therapy with immunosuppressives, despite growing evidence for its benefit. Instead, it considered ‘usual care’, but, given the lack of effective treatment for many patients with Crohn’s disease, such an option constitutes ‘no care’ and continued suffering. Economic analyses should not be the only basis on which decisions regarding the funding of infliximab, or other new agents, are made.
A Randomized Survey of the Preference of Gastroenterologists for a Cochrane Review versus a Traditional Narrative Review
Authors: McDonald John WD , Mahon Jeffrey , Zarnke Kelly , Feagan Brian , Simms Lorinda , Tucker Wayne
Published: March 2016

BACKGROUND: Clinicians often rely on review material rather than analysis of primary research to guide therapy. Systematic reviews use methods to insure thoroughness and to minimize bias, but many clinicians are not familiar with systematic reviews and continue to rely on narrative reviews.

OBEJCTIVES: To determine whether a traditional narrative review or a systematic review is perceived to be more useful.

METHODS: A clinical scenario (patient with chronic Crohn’s disease considered for azathioprine therapy) was circulated to gastroenterologists, along with a narrative review of therapy (including azathioprine) for inflammatory bowel disease written by an acknowledged expert, or with a systematic Cochrane review of the use of azathioprine for this disease. Whether knowledge of authorship and journal source influences the perception of usefulness of a narrative review was investigated.

RESULTS: The Cochrane review was rated significantly more highly than the narrative review on a 100 mm visual analogue scale (21.3 mm; 95% CI 14.5 to 28 mm). The proportion of respondents who considered the review to be a useful guide was also higher in the group that received the Cochrane review (91%) than in the group that received the narrative review, with author and journal concealed (62%) or identified (70%) (P<0.001 for both comparisons). Ratings from the two groups that received the narrative review were not significantly different.

CONCLUSIONS: The focused systematic review was perceived to be more useful than a traditional broad narrative review as a guide to making a decision concerning the use of specific therapy. The possible strengths of systematic reviews should be more fully investigated. If there is additional evidence supporting their greater value to clinicians, they should be made more widely available to clinicians and their strengths should be publicized.
Hepatitis B Viral Mutants and Their Relevance to the Canadian Health Care System
Authors: Minuk Gerald Y
Published: March 2016

Over the past 10 years, an increasing number of mutations in the hepatitis B virus genome have been described. While the majority of these mutations appear to be ‘silent’ or not clinically relevant, some have been described in association with increased severity of disease (core and basic core promoter mutations), evasion of immunological surveillance (S escape mutants), hepatocellular carcinogenesis (X mutants) and resistance to antiviral agents (DNA polymerase mutations). The molecular events and the clinical consequences thereof are reviewed.
Funding the New Biologics – Public Policy Issues in Drug Formulary Decision Making
Authors: Lewis Steven
Published: March 2016

One function of drug formularies is to allow health care providers to exert some control over spending. Decisions about whether to include a given medication in a formulary are based on estimates of its costs and effectiveness, relative to other treatment strategies. These decisions are made from a societal perspective, as opposed to that of individual patients, which sometimes results in conflicts. The clinical response to a medication often varies widely among subjects, which means that a small subgroup of patients might benefit dramatically, while others with the same disease do not. The result would be that a drug might appear not to be cost effective in an economic analysis, even though it is of proven value for some patients. New and innovative medications are assessed according to high standards of cost effectiveness, even though established treatments are wasteful of valuable health care resources. Moreover, quality-adjusted life-years (QALYs) discriminate against certain patient groups, including those with diseases that are associated with a high morbidity but a low mortality. Such patients often incur high indirect costs, including loss of employment income and costs incurred by family caregivers that QALYs do not reflect. Therefore, even though QALYs are transparent and widely applicable, they are not necessarily appropriate in the evaluation of a particular therapeutic intervention. A new paradigm should be developed for evaluating emerging therapies. An example would be a risk-sharing approach, whereby the pharmaceutical industry and public insurers share in the costs and rewards of introducing new treatments. This would have implications for the prices charged for new medications.
The Cost of an Upper Gastroduodenal Endoscopy: An Activity-Based Approach
Authors: Crott Ralph , Makris Nicholaos , Barkun Alan , Fallone Carlo
Published: March 2016

The cost of medical procedures is often unknown, but is nevertheless crucial for setting reimbursement and health care policies. The cost of an upper gastroduodenal endoscopy was investigated in ambulatory adults in a large academic hospital in the province of Quebec, from the perspective of the hospital.

An activity-based costing methodology was used to break down the procedure into a number of priory tasks, to which resources used at the department level (labour, equipment, materials) were allocated. The direct cost of performing an endoscopy ranged from $62 for an unsedated, unbiopsied patient to $89 for a sedated, biopsied patient. Not included in this amount were separate reimbursement fees of $15 for biopsy analysis and the $50 professional fee for the performing physician, which are charged directly to the Ministry of Health.

Incorporating overall, general hospital fixed overhead costs raises the cost of the procedure substantially, by $41, as does the use of nonreusable biopsy forceps, which adds about $63 to the total cost of the procedure.

Given the high proportion of overall, hospital-wide, overhead costs in the total cost of the procedure, allocation methods of these overhead costs in current hospital accounting systems should be improved to obtain a more precise estimate of the full cost of upper gastroduodenal endoscopy.
Motion – Helicobacter pylori Causes or Worsens GERD: Arguments for the Motion
Authors: O’Morain Colm A , Qasim Asghar
Published: March 2016

There are several reasons for eradicating Helicobacter pylori in patients with chronic gastroesophageal reflux disease (GERD). Perhaps the most compelling is the evidence that chronic acid suppression therapy can lead to the development of atrophic gastritis, a premalignant condition, in patients with H pylori infection. Epidemiological data that suggest that H pylori is less prevalent in GERD patients than in control subjects may be susceptible to publication bias, and confounding social and environmental factors may also be involved. Although it has been thought that eradication of the organism might lead to increased esophageal acid exposure, this has not been demonstrated in practice. Studies that appeared to show that GERD could be provoked by antimicrobial therapy of duodenal ulcers also have methodological weaknesses. Underlying GERD symptoms might be unmasked after withdrawal of acid-suppression therapy, for reasons that are unrelated to H pylori. In fact, eradication of the organism has been shown to decrease heartburn in patients with peptic ulcer disease. When H pylori is successfully eradicated in patients with GERD, relapse rates are not increased, and the disease- free interval seems to be prolonged. Eradication of the organism is a wise policy in patients who face long term acid-suppression therapy for GERD.
Leptomeningeal Carcinomatosis Secondary to Gastroesophageal Adenocarcinoma: A Case Report and Review of the Literature
Authors: Abdo Ayman A , Coderre Sylvain , Bridges Ronald J
Published: March 2016

BACKGROUND: Leptomeningeal carcinomatosis (LC) is a rare metastatic complication of solid tumours. It has been mainly described in association with breast cancer, lung cancer and melanoma.

CASE PRESENTATION: A patient presenting with progressive solid food dysphagia with documented adenocarcinoma of the lower esophagus and gastroesophageal junction is reported. One month after the initial diagnosis, the patient developed gradual onset of increasing headache and progressive decrease in the level of consciousness. Computed tomography of the head showed evidence of meningeal enhancement, and cerebrospinal fluid examination showed the presence of adenocarcinoma cells, making the diagnosis of LC. The patient died one month after LC was diagnosed.

DISCUSSION: LC is a poor prognostic sign in solid organ malignancies. It usually presents with headache, altered level of consciousness and focal neurological deficits. Diagnosis is established by finding malignant cells in the cerebrospinal fluid and supported by marked meningeal enhancement on computed tomography of the brain. A review of the English literature found only three reported cases of LC secondary to esophageal malignancy.

CONCLUSION: A case of LC complicating esophageal and gastroesophageal junction malignancy is described. A high index of suspicion and early diagnosis may influence the poor outcome of these patients.
Photodynamic Therapy for Cancer: Principles
Authors: Wilson Brian C
Published: March 2016

The principles of photodynamic therapy (PDT), using drugs (photosensitizers) that are activated by light to become cytotoxic, provide the basis for understanding the current and potential future clinical applications in gastroenterology, general oncology and other specialities. The properties of photosensitizers are key to their biological efficacy, while lasers and optical fibres allow convenient and flexible light delivery for endoscopic use. PDT has several distinct and unique advantages, both as a stand-alone treatment and in combination with other established modalities. The current limitations are also recognized, as is the need for rigorous randomized trials of this emerging technology. The fluorescence of many photosensitizers may be useful, either for (endoscopic) diagnosis or for PDT treatment guidance and monitoring.
Brunner’s Gland Hamartoma: A Rare Cause of Gastrointestinal Bleeding – Case Report and Review of the Literature
Authors: Stolpman David R , Hunt Gordon C , Sheppard Brett , Huang Hahn , Gopal Deepak V
Published: March 2016

An unusual cause of upper gastrointestinal bleeding is described in a previously healthy 45-year-old man who was admitted to hospital with weakness and fatigue, and had experienced an episode of melena two days before admission. His medical and surgical history was unremarkable. Upon admission to hospital, he showed evidence of iron-deficiency anemia, with a hemoglobin concentration of 61 g/L (normal range 135 to 175 g/L), a mean corpuscular volume of 73 fL (normal range 85.0 to 95.0 fL) and a ferritin concentration of 1.0 µg/L (normal range in males 15 to 400 µg/L). Upper gastrointestinal endoscopy revealed a 3.5 cm ulcerated submucosal mass in the third portion of the duodenum, for which mucosal biopsies were nondiagnostic. A subsequent endoscopic ultrasound revealed a 2.7×4.0 cm hyperechoic, cystic, submucosal tumour in the third portion of the duodenum. Endoscopic ultrasound-guided fine needle aspiration revealed no malignant cells. The patient eventually underwent a resection of the third portion of his duodenum. Surgical pathology revealed that this tumour was a Brunner’s gland hamartoma, 4.5 cm in its greatest dimension.
Motion – Prophylactic Banding of Esophageal Varices Is Useful: Arguments for the Motion
Authors: Stiegmann Gregory V
Published: March 2016

Variceal hemorrhage is a frequent complication of cirrhosis and is associated with a high mortality rate, especially in patients with decompensated liver disease. Endoscopy is useful in identifying factors that predict a high likelihood of bleeding, including large varices and red colour signs. Endoscopic rubber band ligation has superseded sclerotherapy in the prevention of both recurrent hemorrhage and the first episode of bleeding, because it causes fewer complications and requires fewer sessions to eradicate varices. It has been proven to be more effective than nontreatment in the primary prophylaxis against variceal hemorrhage. There is extensive literature that has found that band ligation is more effective than beta-adrenergic receptor antagonists at preventing the first variceal hemorrhage. There is ongoing debate about the relative merits of these two approaches, but the available evidence supports the conclusion that band ligation is the treatment of choice in the primary prevention of variceal bleeding. Trials of combined medical and endoscopic therapy are eagerly awaited, and the author suspects that it may prove to be more effective than either modality alone.
Extensive Investigation of Patients with Mild Elevations of Serum Amylase and/or Lipase Is ‘Low Yield’
Authors: Byrne Michael F , Mitchell Robert M , Stiffler Helen , Jowell Paul S , Branch Malcolm S , Pappas Theodore N , Tyler Doug , Baillie John
Published: March 2016

BACKGROUND: Serum amylase and lipase levels are widely used as markers of pancreatic inflammation. However, it would seem that mild elevations of amylase and lipase rarely predict significant pancreatic pathology. Pancreatic imaging tests are expensive. The gold standard, endoscopic retrograde cholangiopancreatography, carries risk of morbidity and mortality.

OBJECTIVE: To determine whether extensive investigation of patients with mild, nonspecific abdominal symptoms and mild elevations of amylase and/or lipase results in a significant diagnostic yield.

METHODS: Outpatient evaluations were retrospectively analyzed over 12 months. Inclusion criteria were nonspecific abdominal pain, and mild elevations (less than three times the upper limit of normal) of serum amylase or lipase, or both. Exclusion criteria included a history of chronic pancreatitis, elevation of liver tests and acute pain syndromes.

RESULTS: Nineteen patients over the study period met the criteria. Of the nineteen patients, 58% had elevation of lipase alone, 21% amylase alone and 21% had elevations of both. In addition, 89.5% of the patients had nonspecific abdominal pain. After imaging with one or more of ultrasound, computed tomography, magnetic resonance cholangiopancreatography, endoscopic ultrasound and endoscopic retrograde cholangiopancreatography, small bowel follow through or hepatobiliary scanning, 78.9% patients were thought to have a normal pancreas. Of the remaining patients, 15.8% had mild or equivocal changes of chronic pancreatitis, and one patient was found to have a pancreatic tail pseudocyst. The average cost of investigation was US$2,255, taking only direct procedural costs into account. No patient was found to have malignancy.

CONCLUSIONS: The majority of patients with nonspecific abdominal pain and isolated elevations of amylase and/or lipase (less than three times the upper limit of normal) had no identifiable pancreatic pathology. The diagnostic yield in patients with mild elevations of lipase alone was particularly poor. The cost effectiveness and risk-benefit ratio of extensive investigation of this group of patients warrants further study.
Motion – Patients with Primary Sclerosing Cholangitis Should Undergo Early Liver Transplantation: Arguments against the Motion
Authors: Crippin Jeffrey S
Published: March 2016

Liver transplantation is an accepted form of treatment for patients with primary sclerosing cholangitis (PSC) and can provide long term survival. Cholangiocarcinoma occurs in 10% to 20% of patients with PSC, is difficult to diagnose and has a poor prognosis. It has been proposed that liver transplantation be undertaken early in the course of the PSC, before cancer develops. Such a proposal would have significant implications for the method of assigning priority to patients awaiting liver transplantation. Other patients on the waiting list would experience further delays, while there is no proven benefit for PSC patients. Few patients with this disease are removed from the waiting list because they developed cancer. If one were to state that PSC patients warrant special consideration because of the hypothetical risk of cholangiocarcinoma, the same argument could be applied to patients with hepatitis C and other causes of cirrhosis, who are at increased risk of hepatocellular carcinoma. The transplant allocation system is applied in an equitable fashion to patients with a large variety of liver diseases. Alteration of this system to benefit a small number of patients with PSC would violate the principles on which it was created, and cannot be justified.
Motion – Prophylactic Banding of Esophageal Varices Is Useful: Arguments against the Motion
Authors: Kowdley Kris V
Published: March 2016

Bleeding from esophageal varices leads to substantial morbidity and mortality. Despite advances in pharmacological and endoscopic therapy, as well as general supportive care, the mortality rate associated with acute variceal hemorrhage has not improved significantly over the past two decades. Prophylactic therapy with nonselective beta-blockers or long acting nitrates reduces the incidence of variceal bleeding in patients with cirrhosis, is cost effective and may improve survival. Surgical portosystemic shunting reduces the risk of bleeding but is associated with significant operative mortality and a high risk of portosystemic encephalopathy. Endoscopic sclerotherapy causes adverse effects in a large proportion of patients and is, therefore, not suitable for primary prophylaxis of bleeding. Although variceal band ligation is effective in reducing the rate of bleeding and is safer than sclerotherapy, it has not been shown to provide a survival advantage compared with beta-blockers. A significant reduction in the rate of variceal bleeding with band ligation, compared with beta-blockers, was shown in only one study. Beta-blockers offer several advantages, including low cost, ease of use and safety. The available data do not yet support the prophylactic use of variceal band ligation, and this procedure should be reserved for patients who are either unwilling or unable to take beta-blockers. It is hoped that additional large, multicentre trials of band ligation versus beta-blockers will examine the efficacy, cost effectiveness and impact on quality of life among patients with cirrhosis.
Tumour Necrosis Factor-Alpha and Nitric Oxide Mediate Apoptosis by D-Galactosamine in a Primary Culture of Rat Hepatocytes: Exacerbation of Cell Death by Cocultured Kupffer Cells
Authors: Abou-Elella Amira Mohamed Kamal ElSaid , Siendones Emilio , Padillo Javier , Montero José Luis , De la Mata Manuel , Relat Jordi Muntané
Published: March 2016

BACKGROUND: Prostaglandin E1(PGE1) reduces cell death in experimental and clinical liver dysfunction.

OBJECTIVES: Whether PGE1protects against d-galactosamine (D-GalN)-associated hepatocyte cell death by the regulation of tumour necrosis factor-alpha (TNF-alpha) and/or nitric oxide (NO) in hepatocytes or cocultured Kupffer cells was examined.

METHODS: Anti-TNF-alpha antibodies were used to evaluate the role of TNF-alpha during d-GalN cytotoxicity and its protection by PGE1in cocultured hepatocytes and Kupffer cells. Cell apoptosis and necrosis were assessed by DNA fragmentation and lactate dehydrogenase release, respectively. Nitrite+nitrate (NOx), as NO end products, and TNF-alpha concentrations were measured in the culture medium. The role of NO was determined by measuring inducible NO synthase (iNOS) expression and the effect of its inhibition during d-GalN cytotoxicity and its protection by PGE1.

RESULTS: d-GalN enhanced hepatocyte cell death associated with high TNF-alpha and NOx levels in a culture medium. Anti-TNF-alpha and iNOS inhibition suggested that TNF-alpha was mediating apoptosis, but not necrosis, through the stimulation of NO production. The antiapoptotic activity of PGE1was associated with a reduction of NO production, but was blocked by iNOS inhibition. This apparent contradiction was explained by the ability of PGE1to enhance iNOS expression shortly after its administration and inhibit it later during d-GalN treatment. Anti-TNF-alpha antibodies did not reduce the exacerbation ofD-GalN-associated cell death in hepatocytes by cocultured Kupffer cells.

CONCLUSION: TNF-alpha mediatesD-GalN-induced apoptosis via NO production in cultured hepatocytes. The protective effect of PGE1againstD-GalN-induced apoptosis is probably through the induction of low iNOS expression that was followed by a reduction of iNOS expression and NO production induced by the hepatotoxin. The exacerbation of hepatocyte cell death by Kupffer cells was not related to TNF-alpha and NO.
Transient Cholestasis in Newborn Infants with Perinatal Asphyxia
Authors: Herzog D , Chessex P , Martin S , Alvarez F
Published: March 2016

In asphyxiated newborn infants, cholestasis often leads to extensive investigations and a cause can rarely be found.

OBJECTIVE: To assess the frequency of transient neonatal cholestasis in an unselected group of asphyxiated newborn infants in a mother-child centre.

METHOD: Charts of 181 asphyxiated newborn infants born with appropriate birth weight for gestational age (AGA) or small weight for gestational age (SGA) at Sainte-Justine Hospital, Montreal, Quebec between 1989 and 1993 were reviewed.

RESULTS: Transient neonatal cholestasis was found in 8.5% of asphyxiated AGA and 33% of SGA newborn infants, compared with 3.94% cholestasis of any etiology in nonasphyxiated SGA infants. Asphyxiated neonates born before the age of 35 weeks had an increased risk for transient neonatal cholestasis (odds ratio 2.84, CI 1.0-8.1).

CONCLUSION: Transient neonatal cholestasis is associated with several contributing factors related to the severity of the neonatal distress. Asphyxia is frequently accompanied by cholestasis in this group of newborns and without symptoms other than uncomplicated cholestasis. Investigations should be focussed on conditions requiring immediate therapy.
Ischemic Colitis after Weight-Loss Medication
Authors: Comay Dan , Ramsay Jennifer , Irvine E Jan
Published: March 2016

BACKGROUND: Previous weight-loss medications have received cautious support due to their association with pulmonary hypertension and valvular heart disease. However, newer drugs are increasingly being recommended as potentially safer and more efficacious. We report a case of ischemic colitis possibly linked to the use of a weight-loss drug, and review the literature to highlight an important latent consequence of these medications.

CASE REPORT: A 59-year-old obese woman presented to the emergency room with rectal bleeding and suprapubic abdominal pain. Her medical history was unremarkable for risk factors for bowel ischemia. An appetite suppressant, phentermine 15 mg daily, had been prescribed, and had resulted in a 12 kg weight loss over 10 weeks. Colonoscopy and biopsies both demonstrated findings typical of mild ischemia at the splenic flexure.

DISCUSSION: Phentermine, an amphetamine-derived sympathomimetic, acts centrally to suppress appetite. While there are no published reports linking the use of phentermine as a single agent to ischemic colitis, phentermine alone has been associated with ischemic neurological events and, when used in combination with fenfluramine, has been implicated in a single case of acute ischemic colitis. Other sympathomimetics, such as cocaine, have been clearly linked with ischemic colitis.

CONCLUSIONS: This report describes a temporal association with the use of phentermine and the development of ischemic colitis. Heightened awareness and appropriate surveillance is warranted to determine whether the use of weight-loss drugs, such as phentermine, can lead to ischemic colitis.
Embolization of a Duodenal Arteriovenous Malformation in Hereditary Hemorrhagic Telangiectasia: Case Report and Review of the Literature
Authors: Inouye Phil , Marcon Norman , Pugash Robin A , Hyland Robert H , Faughnan Marie E
Published: March 2016

A 68-year-old man with hereditary hemorrhagic telangiectasia presented with recurrent, intermittent gastrointestinal hemorrhage. Transfusion of a total of 27 units of red blood cells was required over the three months before admission. Upper and lower endoscopy did not reveal a source of bleeding and a technetium-labelled red blood cell scan was noncontributory. Angiography demonstrated a duodenal arteriovenous malformation originating from a superior mesenteric artery branch. Embolization of the arteriovenous malformation was performed with resolution of gastrointestinal hemorrhage and reduced requirement for blood transfusion. The utility of trans-catheter embolization in the management of duodenal arteriovenous malformations in hereditary hemorrhagic telangiectasia is discussed.
Prognostic Indicators in Acute Pancreatitis
Authors: Imrie Clement W
Published: March 2016

Several approaches have been used in an attempt to predict the severity and prognosis of attacks of acute pancreatitis. The Ranson and Glasgow criteria include a variety of simple laboratory parameters that are measured on admission and again within 48 h. They are the most widely used indices in clinical practice. The Acute Physiological and Chronic Health Evaluation II system is more complicated, but can be applied to a wide variety of conditions, especially in intensive care settings. The usefulness of this system depends on the threshold score for defining severe pancreatitis; a score of eight appears to be the most appropriate. The finding of nonperfused areas in the pancreas at contrast-enhanced computed tomography is indicative of pancreatic necrosis and portends an unfavourable prognosis. Other clinical and laboratory indices have been proposed, but the most important predictive factor of early mortality seems to be the presence and persistance of a Marshall organ failure score of two or more. This is especially true if organ dysfunction persists beyond 36 h. Radiological findings do not always correlate well with the presence of organ dysfunction, and more investigations are required.
Management of Acute Nonvariceal Upper Gastrointestinal Hemorrhage: Comparison of an American and a Canadian Medical Centre
Authors: Targownik Laura E , Gralnek Ian M , Dulai Gareth S , Spiegel Brennan MR , Oei Tommy , Bernstein Charles N
Published: March 2016

OBJECTIVES: Acute nonvariceal upper gastrointestinal hemorrhage (UGIH) remains a common indication for hospital admission. Differences in the structure, process and outcomes of care in the management of acute nonvariceal UGIH between providers in Canada and the United States have not been previously characterized. The aim of the present study was to compare the structure, process and outcomes of care between a Canadian and an American tertiary care medical centre in the management of acute nonvariceal UGIH.

METHODS: Data were collected from identified cases of acute non-variceal UGIH at the two medical centres over two years. Process measures analyzed included the level of care (intensive care unit [ICU] monitored bed versus unmonitored bed) and hospital length of stay (HLOS). Outcomes assessed included rebleeding, inhospital mortality and readmission and/or death within 30 days of admission.

RESULTS: One hundred seventy-five and 83 cases of acute non-variceal UGIH were identified at the American and Canadian centres, respectively. Cases at the American centre had a lower median HLOS, (2.6 versus 3.9 days, P<0.001) but were significantly more likely to be treated in an ICU or monitored setting (67% versus 16%, P<0.001). There were no significant differences in rates of rebleeding or death in hospital or within 30 days of discharge.

CONCLUSIONS: Marked differences exist in the process of care between the Canadian and American medical centres in the management of acute nonvariceal UGIH, despite similar patient severity. Outcomes between the two centres were similar. Minimizing disparity in the process of care of acute UGIH between the two centres may reduce excessive use of resources in the management of acute UGIH without promoting adverse outcomes.
Nonalcoholic Fatty Liver Disease in Patients Investigated for Elevated Liver Enzymes
Authors: Kichian Krikor , Mclean Ross , Gramlich Leah M , Bailey Robert J , G Bain Vincent
Published: March 2016

Nonalcoholic fatty liver disease (NAFLD) is a common diagnosis among patients referred to gastroenterology and hepatology clinics for the evaluation of elevated liver enzymes. The diagnosis of NAFLD is supported by blood work to exclude other liver diseases, and by ultrasound evidence of fat in the liver in patients without a significant history of alcohol intake. The gold standard, however, is a liver biopsy to show the typical histological features of NAFLD, which are almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. A variety of retrospective series have linked NAFLD to obesity, diabetes, hyperlipidemia, total parenteral nutrition, jejunoileal bypass surgery and certain medications. A subset of patients with NAFLD that had an initial presentation of elevated liver enzymes was studied. Two hundred and two patients were reviewed, of whom 49 met the inclusion criteria including a liver biopsy. Patients were excluded if insufficient data were available, if the patients had a significant history of ethanol intake or if they had other coexisting liver disease. These patients were seen between 1996 and 2000 in gastroenterology and hepatology clinics in two community hospitals and one regional liver transplant centre in Edmonton, Alberta. NAFLD was associated with a spectrum of changes in the liver ranging from mild steatosis to more significant steatosis with inflammation and fibrosis. Cases of NAFLD with steatosis and mixed inflammatory infiltration but lacking ballooning degeneration or fibrosis were prevalent in young (20 to 40 years of age) patients with no other significant medical history except for obesity. NAFLD with biopsies showing significant fibrosis and ballooning cell degeneration was associated with obesity, diabetes and older age. It was concluded that, in this predominantly outpatient setting, age over 40 years and diabetes at any age are risk factors for both nonalcoholic steatohepatitis and nonalcoholic steatohepatitis with cirrhosis. It is therefore recommended that patients with raised liver enzymes and suspected NAFLD be targeted for liver biopsy in their evaluation.
Motion-Genetic Testing is Useful in the Diagnosis of Nonhereditary Pancreatic Conditions: Arguments for the Motion
Authors: Whitcomb David C
Published: March 2016

Mutations of three major genes are associated with an increased risk of acute and chronic pancreatitis: the cationic trypsinogen (PRSS1) gene, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and the pancreatic secretory trypsin inhibitor (PSTI) or serine protease inhibitor, Kazal type 1 (SPINK1) gene. Some autosomal dominant forms of hereditary pancreatitis are associated with mutations of thePRSS1gene, which can be readily identified by genetic testing. Mutations of theCFTRgene can lead either to cystic fibrosis or to idiopathic chronic pancreatitis, and to a variety of cystic fibrosis-associated disorders, including congenital bilateral absence of the vas deferens and sinusitis. These mutations, as with those of theSPINK1(orPSTI) gene, are prevalent in North America; thus, the presence of such a mutation in an asymptomatic person does not confer a high risk of developing pancreatitis. Combinations of mutations of thePRSS1andSPINK1genes lead to more severe disease, as indicated by an earlier onset of symptoms, which suggests thatSPINK1is a disease modifier. The major fear expressed by potential candidates for genetic testing is that the results could lead to insurance discrimination. Studies of the positive predictive value of genetic tests are hampered by recruitment bias and lack of knowledge of family history of pancreatitis. Genetic testing is most useful for persons for whom family members have already been found to exhibit a particular pancreatitis-associated mutation. In the future, increased knowledge of the myriad genetic causes of pancreatitis, as well as advances in the diagnosis and treatment of early chronic pancreatitis, should enhance the utility of genetic testing.
Resolution of Multiple Severe Nonsteroidal Anti-Inflammatory Drug-Induced Colonic Strictures with Prednisone Therapy: A Case Report and Review of the Literature
Authors: Penner Robert M , Williams C Noel
Published: March 2016

A 69-year-old woman on nonsteroidal anti-inflammatory drugs (NSAIDs) was admitted to a university hospital with abdominal pain, profound anemia and melena stools. Duodenal ulceration and subsequent healing were documented. Colonoscopy revealed haustral ulceration and NSAID-induced colonic diaphragm disease. Discontinuation of NSAID therapy did not result in endoscopic change, but a 20-week course of prednisone was followed by complete resolution. This is the first case describing prednisone monotherapy for such strictures, and only the second in which endoscopic resolution has been documented. With further supporting experience, prednisone may be considered in addition to NSAID discontinuation for patients with this rare but serious complication.
A New Method of Enteroscopy–The Double-Balloon Method
Authors: Yamamoto Hironori , Sugano Kentaro
Published: March 2016

The diagnosis and treatment of diseases of the small intestine have been impeded by difficult technical challenges. Traditionally, endoscopic evaluation of this organ has required open laparotomy with the surgically assisted passage of the scope through the intestine. Nonsurgical endoscopic techniques have been developed, including push enteroscopy, passage of a scope over a guide-string, and a method that depends on peristalsis to advance the instrument, but each of these is subject to severe limitations. A novel procedure has been devised, whereby an endoscope and a soft flexible overtube, each of which has an inflatable balloon attached to its distal end, are employed together. The technique is described in detail in the present article. Double-balloon enteroscopy allows visualization of the entire small intestine, to and fro examination of an area of interest, and the taking of biopsy specimens in a manner that is safer, quicker and less painful than previous techniques. It constitutes an important advance in the diagnosis and management of bleeding and other small intestinal disorders.
Viral Hepatitis in the Canadian Inuit and First Nations Populations
Authors: Minuk Gerald Y , Uhanova J
Published: March 2016

OBJECTIVE: To review published prevalence data regarding hepatitis A (HAV), B (HBV) and C (HCV) in Canadian Inuit and First Nations populations.

METHODS: PubMed database search and review of all papers describing data derived from seroepidemiological surveys.

RESULTS: The prevalence of anti-HAV positivity in Canadian Inuit and First Nations populations reported to date is high (range 75% to 95%) and approximately three times that of non-Aboriginal Canadians residing in the same communities. Among the Canadian Inuit, the prevalence of HBV infection is approximately 5%, or 20 times that of non-Aboriginal Canadians, while the risk of exposure to HBV is 25%, or five times higher. Regarding the First Nations population, preliminary data suggest the prevalences of HBV infection (0.3% to 3%) and exposure (10% to 22%) are similar to rates in non-Aboriginals residing in the same regions and participating in similar high risk activities. Serological evidence of HCV infection (anti-HCV) is more common in the Canadian Inuit and First Nations (1% to 18%) than the remainder of the Canadian population (0.5% to 2%); however, viremia (HCV-RNA positivity) is less common (less than 5% versus 75% of anti-HCV positive individuals, respectively).

CONCLUSIONS: Viral hepatitis is common in the Canadian Inuit and First Nations populations. In the absence of coexisting human immunodeficiency virus infection and alcohol abuse, the outcomes of HBV and HCV appear to be more benign than in non-Aboriginal Canadians.