Clinical Gastroenterology and Hepatology - Articles in Press

Low dose maintenance therapy with infliximab prevents postsurgical recurrence of Crohn’s disease - Accepted Manuscript

2010-02-08

Abstract: Background & Aims:: Infliximab might prevent post-surgical recurrence of Crohn’s disease. However, it is unclear whether long term therapy with this drug is necessary and whether alternative strategies could be applied, to minimize potential side effects and reduce the costs of treatment.Methods:: We performed a prospective cohort study in 12 consecutive patients, treated immediately after surgery with maintenance infliximab (5 mg/Kg), who did not have clinical or endoscopic evidence of disease recurrence after 24 months; they were followed for an additional year. Treatment with infliximab was then discontinued; patients with disease recurrence, based on endoscopy results (Rutgeerts score ≤2), were given lower doses of infliximab (starting with 1 mg/Kg) in an attempt to re-establish mucosal integrity. Surrogate markers of disease activity (fecal calprotectin [FC], CRP, and ESR) were assessed after each dose of infliximab.Results:: None of the patients had clinical or endoscopic recurrence of Crohn’s disease 3 years after surgery. However, discontinuation of infliximab therapy caused endoscopic recurrence after 4 months in 10/12 patients (83%). All these 10 patients were then treated again with infliximab which, at a dose of 3 mg/Kg every 8-week, restored and mantained mucosal integrity for 1 year. Among the surrogate markers, FC levels correlated with endoscopic scores (Wald test, p < 0.0001).Conclusions:: Long-term maintenance therapy with infliximab is required to maintain mucosal integrity in patients following surgery for Crohn’s disease. However, a dose of 3 mg/Kg (a 40% reduction from the standard dose) was sufficient to avoid disease recurrence, determined by endoscopy, in all patients at one year. FC levels correlate with mucosal status at different infliximab doses.

Sildenafil has no Effect on Portal Pressure but Lowers Arterial Pressure in Patients With Compensated Cirrhosis - Accepted Manuscript

2010-02-08

Abstract: The reduction of portal pressure in patients with early compensated cirrhosis may be more responsive to drugs increasing intrahepatic vasodilatation than those reducing portal venous inflow. The PDE-V inhibitor sildenafil can potentially reduce portal pressure by decreasing intrahepatic resistance, but its systemic vasodilatory effects may be deleterious.Aim:: Evaluate the effect of sildenafil on systemic and portal hemodynamics in an open-label pilot study.Results:: Twelve patients with compensated cirrhosis and baseline hepatic venous pressure gradient (HVPG) >5 mmHg received 25mg of oral sildenafil. Mean arterial pressure(MAP), heart rate (HR) and HVPG were repeated after 30 and 60 minutes and in 9/12 patients at 90 minutes (after an additional 25mg of sildenafil). HVPG tracings were read by 3 blinded observers.Results:: All 12 patients were Child A with median MAP 92 mm Hg(83-94) and median HVPG 10.4 mmHg(6.6-13.0). While MAP decreased significantly at all time points, sildenafil had no effect on HVPG.Conclusion:: As shown with other vasodilators, in compensated cirrhotic patients, sildenafil at therapeutic doses for erectile dysfunction reduces MAP without reducing portal pressure. The search should continue for specific intrahepatic vasodilators.

Abdominal Visceral Adipose Tissue Predicts Risk of Colorectal Adenoma in Both Sexes - Accepted Manuscript

2010-02-08

Abstract: Background & Aims:: Small studies have shown inconsistent results regarding the association between abdominal visceral adipose tissue and colorectal adenomas. We evaluated the effects of visceral adipose tissue volume on the development and growth of colorectal adenomas.Methods:: A total of 3922 participants underwent colonoscopy and computed tomography from February to November 2008. The associations between waist circumference, visceral adipose tissue volume, and colorectal adenomas were estimated with adjusted odds ratios (OR) and 95% confidence intervals (CI). In addition, the association between characteristics of colorectal adenomas and visceral adipose tissue volume were evaluated.Results:: Compared with participants who had visceral adipose tissue volume < 500 cm3, the OR for colorectal adenoma was 1.09 (95% CI, 0.87 to 1.36) for volume of 500–999 cm3, 1.33 (95% CI, 1.04 to 1.69) for volume of 1000–1499 cm3, and 1.43 (95% CI, 1.06 to 1.94) for volume ≥ 1500 cm3. The risk of colorectal adenomas increased with increasing visceral adipose tissue volume in both sexes (P trend = .004 in men and .009 in women). Waist circumference was associated with colorectal adenomas in men (P trend = .02), but not in women. High volume of visceral adipose tissue (≥1000 cm3) had a positive association with larger adenomas (≥10 mm) and multiple adenomas.Conclusions:: Abdominal visceral adipose tissue volume can contribute to the development and growth of colorectal adenomas, and it was a better predictor for risk of colorectal adenomas than body mass index or waist circumference in both sexes.

Tension Hemothorax – a Dreaded Complication of Percutaneous Liver Biopsy - Accepted Manuscript

Ka-Ho Lok, Kin-Kong Li — 2010-02-08

Pancreatic Endocrine Carcinoma Protruding from the Major Papilla - Accepted Manuscript

Junko Umeda, Takao Itoi, Nobuhito Ikeuchi — 2010-02-08

Encapsulating Peritoneal Sclerosis - Accepted Manuscript

Huan-Lun Hsu, Kao-Lang Liu, Jenq-Wen Huang, Kuan-Yu Hung — 2010-02-08

The “Hide-bound” Bowel - Accepted Manuscript

Seth Sweetser, Michael D. Leise — 2010-02-08

Exam 1: The Role of Colonoscopy and Other Procedures in the Management of Acute Lower Intestinal Bleeding - Uncorrected Proof

Charles O. Elson — 2010-02-08

Exam 2: Reduced Hospitalization Cost for Upper Gastrointestinal Events That Occur Among Elderly Veterans who Are Gastroprotected - Uncorrected Proof

Charles O. Elson — 2010-02-08

Reply - Uncorrected Proof

George Triadafilopoulos, Gaurav Arora, Gurkirpal Singh — 2010-02-08

We very much appreciate the comments of van Oijen and colleagues regarding our article on the gastroduodenal damage of aspirin and welcome their overview and suggestions in their submitted Table. We based our suggestion in Figure 2 of our article on evidence that enteric-coated aspirin reduces acute gastric mucosal injury to placebo levels, despite its inhibition of prostaglandin synthesis. Hence our approach represents an appropriate strategy for the prevention of gastric mucosal damage and possible complications, not necessarily dyspepsia only. In a double blind study by Dammann HG et al, enteric-coated aspirin 100 mg/day caused significantly less gastro-duodenal damage over 7 days than the same dose of plain aspirin, when given to healthy subjects. In another short-term study in healthy volunteers, gastric toxicity from aspirin was largely topical, independent of inhibition of prostaglandin synthesis, and could be virtually eliminated by the use of an enteric-coated preparation. At least 5 randomized controlled trials of healthy volunteers undergoing endoscopy after a period of either enteric-coated aspirin or plain aspirin administration all demonstrated a clear reduction of gastric mucosal injury. Further studies will be undoubtedly necessary to clarify these issues while individual patient tolerability and risk will continue to play a role in our decision-making. In the meantime, the suggestion of van Oijen et al is welcome.

Uncorrected Proof

2010-02-05

The rising incidence of adenocarcinoma of the esophagus and the link between symptomatic gastroesophageal reflux and obesity with this cancer are well recognized. This nationwide case-control study of esophageal cancer from Australia sought to identify factors associated with gastroesophageal reflux symptoms and esophageal cancer, as well as any modification by nonsteroidal anti-inflammatory drugs (NSAIDs), smoking, and proton pump inhibitor use. Symptomatic reflux was associated with an increased risk of 6.4 times for esophageal cancer, 4.6 times for gastroesophageal junction cancer (adenocarcinoma), and 2.2 times for squamous cell cancer. Heavy smokers had a markedly higher risk for esophageal cancer than non-smokers (odds ratio, 12.3 vs 6.8), with similar patterns for gastroesophageal junction cancer and squamous cell cancer. Regular use of aspirin or NSAIDs was associated with two-thirds lower risk of esophageal cancer, while no difference was observed with use of acid suppressants.

Success of self-administered home fecal transplantation for chronic Clostridium difficile infection - Accepted Manuscript

Michael S. Silverman, Ian Davis, Dylan R. Pillai — 2010-02-01

Abstract: Clostridium difficile infection (CDI) can relapse in patients with significant comorbidities. A subset of these patients becomes dependent on oral vancomycin therapy for prolonged periods with only temporary clinical improvement. These patients incur significant morbidity from recurrent diarrhea and financial costs from chronic antibiotic therapy. We sought to investigate whether self- or family-administered fecal transplantation could be used to definitively treat refractory CDI. We report a case series (n=7) where 100% clinical success was achieved in treating these individuals with up to 14 months follow up.

High risk ulcer bleeding: when is second look endoscopy recommended? - Accepted Manuscript

Philip Wai Yan Chiu, Joseph Jao Yiu Sung — 2010-02-01

Langerhans cell histiocytosis of the stomach mimicking early gastric cancer - Accepted Manuscript

Yuichi Nozaki, Hisashi Oshiro, Atsushi Nakajima — 2010-02-01

Editor, Clinical Gastroenterology & Hepatology - Accepted Manuscript

Charles Maltz — 2010-02-01

What are the risks of general surgical abdominal operations in patients with cirrhosis? - Accepted Manuscript

J. Michael Henderson — 2010-02-01

Diaphragm-like stricture of the small intestine related to cytomegalovirus infection - Accepted Manuscript

Takahiro Shimizu, Hiroyuki Marusawa, Yukitaka Yamashita — 2010-02-01

Level of Fellowship Training Increases Adenoma Detection Rates - Accepted Manuscript

Stevany L. Peters, Aliya G. Hasan, Nichole B. Jacobson, Gregory L. Austin — 2010-02-01

Abstract: Background & Aims:: The adenoma detection rate (ADR) is critical to the success of colonoscopy for colorectal cancer screening. The effects of involving gastroenterology fellows in screening colonoscopies are uncertain. We assessed the effects of gastroenterology fellow participation on ADR and whether outcomes vary with year of fellowship training.Methods:: We performed a retrospective review of all average-risk screening colonoscopies performed from April 2005 to April 2007 at the University of Colorado Hospital. A gastroenterology attending physician alone performed 2895 colonoscopies; 699 were performed by a gastroenterology fellow supervised by an attending physician. Statistical analyses of polyp, adenoma, and advanced adenoma (or cancer) detection were performed using logistic regression.Results:: The ADR was significantly higher (odds ratio [OR]=1.32, 95% CI: 1.10-1.59) among colonoscopies that included a gastroenterology fellow compared to those performed by only a gastroenterology attending physician. Similarly, the polyp detection rate was higher (OR=1.28, 95% CI: 1.08-1.52) among colonoscopies involving a gastroenterology fellow. There was no difference in the detection of advanced adenomas or cancers (OR=1.05, 95% CI: 0.77-1.44) among colonoscopies involving a gastroenterology fellow. The ADR differed greatly by year of training. Compared to colonoscopies performed by an attending gastroenterologist alone, the ADR increased with each year of training: OR=0.89 (95% CI: 0.66-1.22) for first-year fellows; OR=1.31 (95% CI: 0.89-1.93) for second-year fellows; and OR=1.70 (95% CI: 1.33-2.17) for third-year fellows.Conclusion:: Involvement of fellows in screening colonoscopies increases the ADR, primarily because of the increased ADR in procedures involving third-year gastroenterology fellows.

Continuous Therapy With Certolizumab Pegol Maintains Remission of Patients With Crohn’s Disease for up to 18 Months - Accepted Manuscript

2010-02-01

Abstract: Background & Aims:: The safety and efficacy of maintenance therapy with the anti-tumor necrosis factor antibody fragment certolizumab pegol has not been reported beyond 6 months. We assessed the long-term efficacy, safety, and immunogenicity of continuous vs interrupted maintenance therapy with subcutaneous certolizumab pegol in patients with Crohn’s disease.Methods:: Patients who responded to induction therapy at week 6 of the PRECiSE 2 trial were randomly assigned to groups given certolizumab pegol (continuous) or placebo (drug-interruption) during weeks 6–26. Patients who completed PRECiSE 2 were eligible to enter PRECiSE 3, an ongoing, open-label extension trial where patients have received certolizumab pegol (400 mg) every 4 weeks for 54 weeks to date (total of 80 weeks). Disease activity was measured by the Harvey-Bradshaw Index. PRECiSE 3 is the first prospective trial in which patients received continuous or interrupted anti–TNF-α therapy >12 months and were not offered the option to increase their dose.Results:: Harvey-Bradshaw Index responses at week 26 for the continuous and drug-interruption groups were 56.3% and 37.6%, respectively; corresponding remission rates were 47.9% and 32.4%, respectively. Of patients responding at week 26, response rates at week 80 in the continuous and drug-interruption groups were 66.1% and 63.3%, respectively; among patients in remission at week 26, week 80 remission rates were 62.1% and 63.2%, respectively. More patients in the drug-interruption group developed antibodies against certolizumab pegol (and had lower plasma concentrations of certolizumab pegol) than the continuously treated group.Conclusions:: Certolizumab pegol effectively maintains remission of Crohn’s disease for up to 18 months. Continuous therapy is more effective than interrupted therapy.

Exam 1: Risk of Esophageal Adenocarcinoma and Mortality in Patients With Barrett's Esophagus: A Systematic Review and Meta-analysis - Uncorrected Proof

C. Mel Wilcox — 2010-01-22

Correlation Between the Crohn's Disease Activity and Harvey-Bradshaw Indices In Assessing Crohn's Disease Severity - Uncorrected Proof

2010-01-21

Background & Aims: Clinical trials of Crohn's disease generally use the Crohn's Disease Activity Index to assess disease activity; these calculations are complex, time-consuming, and impracticable. We investigated whether a simpler tool, the Harvey-Bradshaw Index, was equally effective in assessing disease severity.Methods: Crohn's Disease Activity and Harvey-Bradshaw Index scores were collected from 2 large multicenter Crohn's disease studies. The PEGylated antibody fragment evaluation in Crohn's disease: safety and efficacy (PRECiSE) 1 and 2 trials assessed efficacy and tolerability of certolizumab pegol (PEGylated, humanized, Fab' fragment of an antitumor necrosis factor α antibody). PRECiSE 1 and 2 data were analyzed to determine if results from the Crohn's Disease Activity Index correlated with those from the Harvey-Bradshaw Index criteria for defining response and remission.Results: Analysis of almost 1000 data pairs showed a positive correlation between scores. The correlation between the indices for pooled data from PRECiSE 1 and PRECiSE 2 was 0.800 (Spearman correlation coefficient). The correlations between indices for the PRECiSE 1 or PRECiSE 2 were 20.698 and 0.716, respectively (Kronecker product variance). A 3-point change in the Harvey-Bradshaw Index score corresponded to a 100-point change in the Crohn's Disease Activity Index (clinical response); scores ≤4 points corresponded to a Crohn's Disease Activity Index score ≤150 points (clinical remission).Conclusions: Results from the Crohn's Disease Activity Index correlate with those from the Harvey-Bradshaw Index; use of the Harvey-Bradshaw Index might permit simpler Crohn's disease activity assessment in long term clinical trials, and facilitate standardized disease activity measurements and cross-center comparisons.

Reduced Hospitalization Cost For Upper Gastrointestinal Events That Occur Among Elderly Veterans Who Are Gastroprotected - Uncorrected Proof

Neena S. Abraham, Christine Hartman, Jennifer Hasche — 2010-01-21

Background & Aims: Despite prescription of gastroprotection among elderly nonsteroidal anti-inflammatory drug (NSAID) users, residual bleeding can still occur. We sought to determine the effect of proton pump inhibitors (PPI) on hospitalization and resource use among veterans in whom an upper gastrointestinal event (UGIE) occurred.Methods: We identified from national pharmacy records veterans ≥65 years prescribed an NSAID, cyclooxygenase-2 selective NSAID (coxib), or salicylate (>325 mg/day) at any Veterans Affairs (VA) facility (01/01/00–12/31/04). Prescription fill data were linked longitudinally to a Veterans Affairs-Medicare dataset of inpatient, outpatient, and death files, and demographic and provider data. Among veterans in whom a UGIE occurred, we assessed the effect of prescription strategy on hospitalization, using a multivariate logistic regression model.Results: A total of 3566 UGIEs occurred among a cohort that was predominantly male (97.5%), white (77%), with a mean age of 73.5 (SD, 5.7). Hospitalization occurred in 47.5%, and gastroprotection was associated with a 30% reduction in hospitalization compared with no PPI. Five-year pharmacy costs associated with the PPI strategy exceeded the no-PPI strategy ($742,406 vs $184,282); however, a substantial reduction in medical costs was observed with PPI ($9,948,738 vs $18, 686,081).Conclusions: Even if an NSAID-UGIE occurs in the PPI-protected older veteran, the reduction in need for hospitalization results in a cost saving to the Department of Veterans Affairs.

Reply - Uncorrected Proof

Peter Bacchetti, Uri Ladabaum — 2010-01-21

We thank Drs Ford and Moayyedi for their comment on our paper. This provides us with an opportunity to emphasize a principle that is important both for our paper and more generally: power is not relevant for interpreting completed studies. This has been discussed in several articles, and the explanation document for the Consolidated Standards of Reporting Trials (CONSORT) guidelines states, “There is little merit in calculating the statistical power once the results of the trial are known.”

Exam 2: Acute Pancreatitis: Computed Tomography Utilization and Radiation Exposure Are Related to Severity but Not Patient Age - Uncorrected Proof

Charles O. Elson — 2010-01-21

Duodenal Ulceration Following Variceal Embolization with Coils and Vascular Plugs - Accepted Manuscript

Anshu Mahajan, Sean C. Kumer, Andrew Y. Wang — 2010-01-07

Gastric Anisakiasis - Accepted Manuscript

Mamatha Bhat, Paul Cleland — 2010-01-07

Necrolytic migratory erythema due to glucagonoma - Accepted Manuscript

Guido Michels, Dirk Nierhoff, Hans-Michael Steffen — 2010-01-07

Increased incidence of small intestinal bacterial overgrowth during Proton Pump Inhibitor therapy - Accepted Manuscript

Lucio Lombardo, Monica Foti, Olga Ruggia, Andrea Chiecchio — 2010-01-07

Abstract: Background & Aims:: Proton pump inhibitors (PPIs) can cause diarrhea and enteric infections and alter the gastrointestinal bacterial population by suppressing the gastric acid barrier. Among patients that received long-term PPI treatment, we evaluated the incidence of small intestinal bacterial overgrowth (SIBO; assessed by glucose hydrogen breath test [GHBT]), the risk factors for development of PPI-related SIBO and its clinical manifestations, and the eradication rate of SIBO after treatment with rifaximin.Methods:: GHBTs were given to 450 consecutive patients (200 with gastroesophageal reflux disease that received PPIs for a median of 36 months; 200 with irritable bowel syndrome, in absence of PPI treatment, for at least 3 years; and 50 healthy controls that had not received PPI for at least 10 years). Each subject was given a symptoms questionnaire.Results:: SIBO was detected in 50% of patients on PPIs, 24.5% of patients with IBS, and 6% of healthy controls; there was a statistically significant difference between patients on PPIs and those with IBS or healthy controls (p<0.001). The prevalence of SIBO increased after 1 year of treatment with PPI. Bloating and weight loss were more frequent among patients with PPI-related SIBO than those with IBS-related SIBO. The eradication rate of SIBO was 87% in the PPI group and 91% in the IBS group.Conclusions:: SIBO, assessed by GHBT, occurs significantly more frequently among long-term PPI users than patients with IBS or controls. High-dose therapy with rifaximin eradicated 87%–91% cases of SIBO in patients that continued PPI therapy.

Gluten-Free Diet and Steroid Treatment Are Effective Therapy for Most Patients With Collagenous Sprue - Uncorrected Proof

2010-01-07

Background & aims: Collagenous sprue (CS) is characterized by the presence of a distinctive band of subepithelial collagen deposition in the small bowel. We evaluated the clinical characteristics, treatments, and outcomes of patients with CS.Methods: Thirty patients with CS were identified at the 3 Mayo Clinic sites between 1993 and 2009. Clinical data from medical records were reviewed.Results: The study cohort was 70% female (age range, 53–91 years). Most patients had severe diarrhea and weight loss. Hospitalization to treat dehydration was necessary in 16 (53%) patients. Associated immune-mediated diseases were noted in 70% of the patients; celiac disease was the most frequent. Other associated diseases were microscopic colitis, hypothyroidism, and autoimmune enteropathy. The median thickness of the layer of subepithelial collagen deposition in the small bowel was 29 μm (20–56.5 μm). Subepithelial collagen deposition in the colon or stomach was noted in 8 patients. A clinical response was observed in 24 (80%) patients after treatment with a combination of a gluten-free diet and immunosuppressive drugs. Histologic improvement was confirmed in 9 patients, with complete remission in 5. Two patients died (1 of complications of CS and 1 of another illness).Conclusions: Most patients with CS are treated effectively with a combination of gluten-free diet and steroids. CS is often associated with collagen deposition or chronic inflammation in other segments of the gastrointestinal tract as well as other immune-mediated disorders.

Systematic Review of the Quality of Patient Information on the Internet Regarding Inflammatory Bowel Disease Treatments - Uncorrected Proof

2010-01-07

Background & aims: Patients use the Internet as a resource for information about their diseases. A systematic review evaluating the quality of information available for inflammatory bowel disease patients on the Internet regarding treatment options was performed.Methods: Google was used to identify 50 websites on 3 occasions. A data quality score (DQS) (potential score, 0–76) was developed to evaluate the content of websites that scores patient information on indications, efficacy, and side effects of treatment. Other outcome measures were a 5-point global quality score, a drug category quality score, the DISCERN instrument, a reading grade level score, and information about integrity.Results: The median DQS was 22, range 0–74, median global quality score was 2.0, and median Flesch-Kincaid reading grade level was 12.0, range 6.9–13.7. Eight websites achieved a global quality score of 4 or 5. The DQS was highly associated with the global quality score (r = 0.82) and the DISCERN instrument (r = 0.89). There was poor association between the DQS and the rank order in all 3 Google searches. Information on funding source (54%) and date of last update (56%) were often lacking.Conclusions: There is marked variation in the quality of available patient information on websites about the treatment options for Crohn's disease and ulcerative colitis. Few websites provided high quality information. There is a need for high quality accredited websites that provide patient-oriented information on treatment options, and these sites need to be updated regularly.

Reflux Is Unlikely to Occur During Stable Sleep - Uncorrected Proof

John Dent — 2010-01-07

Dear Editor: Regrettably, the article by Gagliardi et al in the September 2009 issue of Clinical Gastroenterology and Hepatology inappropriately reinforces, both in its title and in its contents, the unproven assertion that reflux occurs during stable sleep. Also regrettably, the accompanying editorial by Harding endorses the concept that nocturnal reflux occurs predominantly during stable sleep, even though the important interaction of sleep with transient lower esophageal relaxations is recognized in this editorial.

Osteonecrosis and Panniculitis as Life-Threatening Signs - Uncorrected Proof

Masaki Kuwatani, Hiroshi Kawakami, Yosuke Yamada — 2010-01-07

A 58-year-old male presented with polyarthritis in the bilateral wrists and ankles, and elevated serum pancreatic enzymes (amylase, 4292 IU/L; lipase, 6000 IU/L). He previously had several episodes of acute pancreatitis, and had undergone cholangiojejunostomy for alcoholic chronic pancreatitis with a pseudocyst and stricture of the lower bile duct 6 years ago. Although pancreatic enzymes were temporarily normalized, roentgenograms exhibited osteonecrosis in 4 extremities 1 year after the development of polyarthritis (). Examination of a biopsy specimen of the left femur revealed intraosseous fat necrosis. A computerized tomography scan performed just before admission to our department revealed slight dilatation of the main pancreatic duct and a cystic lesion adjacent to the superior mesenteric vein (SMV) in the pancreas head (). On admission, serological examinations indicated liver and renal dysfunction (elevated serum levels of aspartate aminotransferase [238 IU/L], alanine aminotransferase [167 IU/L], γ-GT [101 IU/L], blood urea nitrogen [49 mg/dL], and creatinine [1.9 mg/dL]), and elevated levels of pancreatic enzymes (amylase, 7966 IU/L; lipase, 12,904 IU/L). Physical findings were erythema in the abdomen () and purpura in bilateral lower extremities. Renal dysfunction rapidly exacerbated and he died 5 days after admission to our department. After informed consent from his family, autopsy was done. Gross findings of specimens of the pancreas head and the peripancreatic tissue showed a fistula between the cystic lesion in the pancreas head and SMV, and exposure of debris from the cystic lesion. Microscopically, the cystic lesion was a pseudocyst connecting to the SMV, and the debris was protein plaque. The pancreas tissue surrounding the lower bile duct showed fibrous change and atrophy of the acini. In the kidneys, glomerular crescent formation was diffusely found, and a part of basement membrane was necrotic. In the skin, fibrinoid changes and infiltration of inflammatory cells were found in the walls of small arteries, and there was nodular fat necrosis with calcification (), which was also found in other organs including gastric subserosa and bone marrow. Finally, we made a diagnosis of PPP syndrome caused by pancreatic pseudocyst-portal vein fistula.

Positive Response To Steroid Therapy For Autoimmune Pancreatitis Evaluated With Fluorodeoxyglucose Positron Emission Tomography - Uncorrected Proof

Kensuke Takuma, Terumi Kamisawa, Takao Itoi — 2010-01-07

A 45-year-old man with a history of excessive alcohol consumption visited a general practitioner due to sudden severe abdominal and back pain. Moderately elevated serum amylase indicated acute pancreatitis. Although the symptoms were relieved by conservative medical management within a few days, he was referred to our hospital because a computerized tomography (CT) scan revealed a mass in the pancreatic tail. A detailed CT scan showed an enlarged pancreas with encasement of the splenic artery, obstruction of the splenic vein, a growth that had invaded the retroperitoneum (), a hepatic mass of 2 cm and parabronchial lymphadenopathy. The main pancreatic duct was not detected in the pancreatic tail on magnetic resonance cholangiopancreatography (MRCP), and endoscopic retrograde cholangiopancreatography (ERCP) failed. The pancreatic and hepatic lesions appeared as high-intensity areas on diffusion-weighted magnetic resonance imaging (MRI). Positron emission tomography (PET) scans also revealed intense fluorodeoxyglucose (FDG) uptake in the pancreatic (, panel 1, and , panel 1, long arrow) and hepatic lesions (, panel 1, short arrow), as well as in the parabronchial and mediastinal lymph nodes (, panel 1, arrow heads). The imaging findings indicated advanced pancreatic cancer with hepatic and extensive lymph node metastases, but laboratory findings, including tumor markers such as CA19.9 and CEA, and serum IgG4 levels were normal. However, because the enhancement was delayed in the enlarged pancreas, we performed endoscopic ultrasonography (EUS)-guided fine needle aspiration before administrating chemotherapy. Histological examination of the obtained pancreatic tissue revealed dense fibrosis with abundant infiltration of lymphocytes and IgG4-positive cells, but no cancer cells (). Steroid therapy with oral prednisolone (30 mg/day) was started considering a diagnosis of autoimmune pancreatitis with extensive extrapancreatic lesions. Two months later, FDG uptake had vanished on FDG-PET scan (, panel 2, and , panel 2).

An Unusual Presentation of Hematemesis: Maxillary Metastasis from Hepatocellular Carcinoma - Uncorrected Proof

Ming-Jong Bair, Wei-Yi Lei, Chien-Lin Chen — 2010-01-07

A 52 year-old man with a past medical history of alcoholic liver cirrhosis presented with production of increasing volume of blood-stained sputum and hematemesis. Physical examination disclosed pale conjunctiva, jaundice, and a 2.0 cm, firm, protruding mass with surrounding erythema on his upper anterior maxilla ().

Refractory Lymphocytic Enterocolitis and Tumor Necrosis Factor Antagonist Therapy - Uncorrected Proof

2009-12-28

Background & Aims: Lymphocytic enterocolitis is a malabsorptive syndrome characterized by severe small-bowel villous abnormality and crypt hyperplasia and dense infiltrate of lymphocytes throughout the gastrointestinal tract.Methods: We present 2 patients with lymphocytic enterocolitis refractory to usual medical therapy who were treated with tumor necrosis factor antagonists.Results: Both patients had clinical improvement in diarrheal symptoms and intestinal histologic abnormalities.Conclusions: Tumor necrosis factor-α antagonists such as infliximab or adalimumab may be a new treatment option for patients with severe refractory lymphocytic enterocolitis not responding to corticosteroids.

Title - Uncorrected Proof

2009-12-28

Dear Editor: We have read the editorial by Triadafilopoulus with interest. It covers the important results of the EURO-I study using radiofrequency for treatment of neoplastic Barrett's esophagus. To our surprise, the author quotes the German general Heinz Wilhelm Guderian several times. Heinz Wilhelm Guderian was responsible for the severe attacks on the Polish and Russian civilian population during World War II and was appointed by Hitler to the position of Chief of General Staff of the German Wehrmacht after the failed assassination attempt on Hitler June 20th 1944 (Operation Walküre). After the war, he was a prisoner of war until 1948 and thereafter supposed to be a member of the “Bruderschaft” (fraternity), an organization of elder Nazis founded to sabotage the newly formed Federal Republic of Germany (West Germany).

Cardiac Dysphagia - Uncorrected Proof

Klaus Mönkemüller, Klaus Feldmann, Ludger J. Ulbricht — 2009-12-28

An 82-year-old woman was admitted because of failure to thrive and dysphagia to solids. The patient complained of decreased appetite and a 15-lb weight loss over a 10-month period. In addition, she complained of hoarseness for about 2 years. Her past medical history was significant for chronic atrial fibrillation and mitral regurgitation grade II caused by a mitral valve prolapse of the anterior leaflet. The atrial fibrillation was treated medically and with a VVI-R pacemaker, after a failed electric cardioversion 12 years previously. Clinical examination revealed an elderly woman in no apparent distress. The heart showed a paced regular rhythm at the cut-off rate of the implanted pacemaker. A radiograph of the chest showed cardiomegaly and moderate pulmonary edema. Echocardiography showed a giant left atrium measuring 7.5 × 9.0 cm and the underlying mitral valve prolapse with regurgitation II ( A). An esophagogastroduodenoscopy disclosed a partially paralyzed left vocal cord and esophageal stenosis caused by extrinsic compression located from 28 to 33 cm from the incisors ( B). The esophageal lumen could be expanded partially by giving constant air insufflation and the stenosis could be passed easily by gently pushing and advancing the scope distally. The distal 5 cm of esophagus were normal. A computed tomography of the chest excluded mediastinal tumors and confirmed the giant left atrium. The giant left atrium sandwiched the esophagus against the aorta and the spine, completely compressing the esophageal lumen for a segment of about 5 to 6 cm ( C). The patient was treated for heart failure with gradual improvement of her symptoms. However, the vocal cord paralysis persisted.

Factors That Predict Outcome of Abdominal Operations in Patients With Advanced Cirrhosis - Corrected Proof

2009-12-28

Background & Aims: Patients with cirrhosis have an increased risk of complications during surgery that is relative to the severity of liver disease; it is a challenge to determine which patients are the best candidates for surgery. We performed a hospital-based study to identify factors that might facilitate selection of operative candidates and guide their management.Methods: A retrospective review was performed of 100 cirrhotic patients (50 classified as Child–Turcotte–Pugh [CTP] A, 33 as CTP B, and 17 as CTP C) who underwent abdominal surgery at an institution specializing in liver medicine and transplant from 2002–2008. Significant univariate variables were evaluated by multivariate logistic regression models to identify factors that correlate with outcome.Results: The overall, 30-day postoperative mortality rate was 7%. The mortality for patients who were CTP A was 2%, CTP B was 12%, and CTP C was 12%; 33 patients had a Model for End-Stage Liver Disease (MELD) score ≥15, with 29% mortality. On the basis of multivariate analyses, risk factors for adverse outcome were American Society of Anesthesiologists (ASA) score >3; procedures being emergent; intraoperative blood transfusion; intraoperative blood loss >150 mL; presence of ascites; total bilirubin level >1.5 mg/dL; and albumin level <3 mg/dL. Addition of serum albumin to MELD score showed that patients with MELD score ≥15 and albumin ≤2.5 mg/dL (vs >2.5 mg/dL) had significantly increased mortality (60% vs 14%, P < .01) and independently increased probability of adverse outcome (odds ratio, 8.4; P = .015).Conclusions: For patients with MELD scores ≥15, the preoperative albumin level correlates with outcome and could guide operative decisions. Intraoperative packed red blood cell transfusion correlates with adverse outcome and should be limited.

Danish Patients With Chronic Pancreatitis Have a Four-Fold Higher Mortality Rate Than the Population - Uncorrected Proof

2009-12-28

Background & Aims: We investigated mortality of patients with chronic pancreatitis (CP), compared with the population and sought to determine whether clinical presentations of CP can be used in prognosis. We also investigated clinical factors associated with mortality and causes of death among these patients.Methods: The Copenhagen Pancreatitis Study is a prospective study of patients admitted from 1977 to 1982 to the 5 main hospitals in Copenhagen with a diagnosis of acute pancreatitis or CP. In 2008, follow-up data were collected from these patients from the Danish Registries; this subcohort comprised 290 patients with probable (n = 41) or definite CP (n = 249).Results: The mortality of patients with definite CP was 4-fold that of the Danish population and significantly higher than that of patients with probable CP (P = .003; 95% confidence interval [CI], 1.21–2.57); patients with probable CP had a 2- to 3-fold higher mortality rate than the population. In patients with definite CP, factors significantly associated with mortality included unemployment (P = .015; 95% CI, 0.53–0.93), and being underweight (P = .020; 95% CI, 0.52–0.95). Sex, alcohol use, smoking, single versus co-living, exocrine insufficiency, diabetes, pancreatic calcification, CP inheritance, painless CP, acute exacerbation of CP, or surgery for CP had no impact on survival. The most frequent causes of death were digestive diseases (19.5%), malignancies (19.5%), and cardiovascular diseases (11.3%).Conclusions: Danish patients with definite CP had a 4-fold higher mortality rate compared with the background population and a higher mortality rate than patients with probable CP. Being unemployed or underweight had significant impact on survival.

The Role of Colonoscopy and Radiological Procedures in the Management of Acute Lower Intestinal Bleeding - Corrected Proof

Lisa L. Strate, Christopher R. Naumann — 2009-12-28

There are multiple strategies for evaluating and treating lower intestinal bleeding (LIB). Colonoscopy has become the preferred initial test for most patients with LIB because of its diagnostic and therapeutic capabilities and its safety. However, few studies have directly compared colonoscopy with other techniques and there are controversies regarding the optimal timing of colonoscopy, the importance of colon preparation, the prevalence of stigmata of hemorrhage, and the efficacy of endoscopic hemostasis. Angiography, radionuclide scintigraphy, and multidetector computed tomography scanning are complementary modalities, but the requirement of active bleeding at the time of the examination limits their routine use. In addition, angiography can result in serious complications. This review summarizes the available evidence regarding colonoscopy and radiographic studies in the management of acute LIB.

Gastrojejunocolic Fistula Overlooked as an Ulcer in Endoscopy - Accepted Manuscript

Pin-Chao Wang, Chih-Hsin Lee, Chia-Chi Wang — 2009-12-25

Esophageal Intramural Pseudodiverticulosis: A Rare Cause of Esophageal Stricture - Accepted Manuscript

Shunsuke Yamamoto, Shusaku Tsutsui, Norio Hayashi — 2009-12-25

Update on Colonoscopic Imaging and Projections for the Future - Uncorrected Proof

Douglas K. Rex — 2009-12-21

Recently, a large number of articles on new colonoscopic imaging technologies has appeared, and this issue of Clinical Gastroenterology and Hepatology has 3 more such articles. This editorial reviews the current state of the art on colonoscopic imaging technologies and their clinical potential.

Risk and Reason in Barrett's Esophagus - Uncorrected Proof

Nicholas J. Shaheen — 2009-12-18

Most gastroenterologists have had the experience. The recently endoscoped patient meets with you for the postendoscopy debriefing. It is your duty to inform the patient of the presence of Barrett's esophagus (BE), a change in the lining of the esophagus that is associated with an increased risk of esophageal cancer. “But the good news is, the risk of cancer is low,” you report in an encouraging tone. The patient leaves with refills of the proton pump inhibitor prescription, and a plan for follow-up endoscopy.

Disconnected Pancreatic Duct With Pancreas Necrosis, Treated With Transgastric Debridement and Pancreatic Duct Stent - Corrected Proof

Kapil Gupta, Martin L. Freeman — 2009-12-14

A 75-year-old man presented 6 weeks after onset of severe acute biliary pancreatitis with low grade fever and malaise. Computerized tomography scan demonstrated infected organized necrosis of the central portion of the pancreas demonstrated by a circumscribed area of heterogeneous nonenhanced pancreas containing pockets of air (). Due to poor medical condition, he was treated with endoscopic ultrasound-guided cyst gastrostomy with placement of double pigtail stents extending from the stomach lumen into the cyst cavity, with drainage of purulent material. One week later this was followed by repeated direct endoscopic debridement of white necrotic material using a forward viewing endoscope passed per oral route through the cystgastrostomy into the cavity. Endoscopic retrograde cholangiopancreatography (ERCP) was also performed with placement of a transpapillary pancreatic stent through a disrupted pancreatic duct into the cavity in the middle of the pancreas ( B). After 3 endoscopic sessions of debridement (), healthy granulation tissue and the end of the transpapillary stent protruding through the disconnected pancreatic duct into the cavity are visualized in the cyst cavity (). A small pinpoint opening of the upstream disconnected duct is seen (), which is confirmed by injecting contrast as representing the upstream end of the disconnected duct (). Follow-up computerized tomography scan after removal of cystgastrostomy stents shows complete resolution of the cavity, months after the initial procedure ().

Adenosquamous Carcinoma of the Pancreas - Corrected Proof

Kunihiko Izuishi, Ryusuke Takebayashi, Yasuyuki Suzuki — 2009-12-14

A 70-year-old man was admitted to the hospital because of general fatigue. His serum tumor marker levels for carbohydrate antigen 19-9 was significantly elevated to 2975 U/mL (the normal range is <38 U/mL). A computerized tomography scan imaging of the abdomen showed a low density huge solid mass, approximately 10 cm in diameter in the tail of the pancreas ( A). Fluorodeoxyglucose positron emission tomography (FDG-PET) showed a strong FDG uptake, with maximum standardized uptake value (SUV) of 15.8 ( B). In a staging laparoscopy, we did not find any inoperable factors, such as peritoneal dissemination or liver deposits. Therefore, 7 days after the staging laparoscopy, we performed an extended pancreatectomy, which included resection of the spleen, the stomach, and the left kidney. The patient died 7 months after the operation because of liver metastasis. The histological diagnosis was adenosquamous carcinoma which had 2 components: a poorly differentiated adenocarcinoma with mucin production ( C) and squamous cell carcinoma with keratinization ( D).

Personalized Dose Reduction for Computed Tomography Scanning: Size Matters, so Does Prior Radiation Exposures - Corrected Proof

Mannudeep K. Kalra, Isaac R. Francis — 2009-12-14

The article, “Acute Pancreatitis: Computed Tomography Utilization and Radiation Exposure Are Related to Severity but Not Patient Age” by Morgan et al1 is timely and a valuable addition to the existing literature written on the subject of radiation dose in patients undergoing repetitive computed tomography (CT) scans. We agree with the points made by the authors and several other investigators who recently have written and commented on the subject of excessive radiation dose caused by imaging and its reduction. In this clinical setting, the referring physicians, gastroenterologists, surgeons, and radiologists should work together as a team to eliminate unnecessary routine CT scanning and utilize ultrasound or magnetic resonance imaging (MRI) if the needed information can be obtained with these nonionizing imaging modalities. However, if the desired information can be obtained only with CT, dose reduction techniques should be used that effectively reduce radiation dose to the patient without sacrificing diagnostic information.

Acute Pancreatitis Part II: Approach to Follow-up - Uncorrected Proof

Bechien U. Wu, Darwin L. Conwell — 2009-12-14

A 51-year-old man is preparing for discharge following his first episode of acute pancreatitis. He presented to the emergency ward with abdominal pain, nausea, and vomiting. Acute pancreatitis was confirmed by elevations in the amylase and lipase greater than 3 times the upper limit of normal (amylase 9000 U/L and lipase 10,700 U/L). Gallstones were the suspected etiology of pancreatitis based on elevations in the liver biochemical profile (aspartate transaminase, 84; alanine transaminase, 147; alkaline phosphatase, 356; total bilirubin, 5.5). This was confirmed by findings of choledocholithiasis on abdominal ultrasound.

Medical Economies 2009 - Corrected Proof

Barry Kisloff — 2009-12-14

Dear Editor: Congratulations on the publication of an overview of the current state of medical economics as it relates to gastroenterology. Several items raised in this review merit further comment. First, when a nation's wealth increases, so does its spending on health care. Although the United States does spend more per capita on health care than any other nation, other newly prosperous countries are increasing the proportion of their spending for health services at a rate that exceeds the United States. Second, the “successful” health care systems of the Common Market are under severe duress as costs vastly outpace the ability to finance these systems. Third, comparative effectiveness research will never alter current practice without tort reform. As long as litigation can proceed without dollar limits and adherence to published guidelines does not offer absolute or near-absolute protection from wanton litigation, no practitioner will adhere to guidelines when a bad outcome can result in tort misery. Fourth, mixed payment models are a sophist's euphemism for decreased payment to all physicians, but particularly medical specialists. When monies are supplied in a bulk payment to a large medical organization, the inevitable scenario involves the highly centralized administration of the organization distributing payments to the unorganized/poorly organized physicians in a manner that best meets the needs of the proverbial “overall organization.” We already have been witness to this financial chicanery as large groups having a common tax identification number distribute Medicare's Physician Quality Reporting Initiative (PQRI) dollars for “special” projects rather than to the physicians who earned the money. Fifth, let us be clear, when it comes to the verbiage of payment for health care services, bundling equals chiseling on payments to the provider. Sixth, Centers for Medicare and Medicaid Services (CMS) “never events” include such items as the ludicrous nonpayment for events subsequent to falls and nonpayment for post–knee replacement deep venous thrombosis. Thus, CMS cavalierly has repealed the law of gravity and made our efforts at antithrombosis completely effective. Making postpolypectomy bleeding a “never event” will lead most fiscally savvy gastroenterologists to avoid those patients with even a whiff of risk for postpolypectomy hemorrhage. Seventh, dividing the Sustainable Growth Rate (SGR) into evaluation and management (E&M) and non-E&M segments ignores the fact that new technology is a prime driving force in the upward cost curve for health care. Such a division of the SGR would effectively end subspecialty medicine because even the most venal practitioner who mercilessly churns his/her practice to enhance income would be unable to maintain an adequate revenue stream in the face of mandated decreases in procedure relative value unit value. Eighth, not mentioned in the article is CMS's decision to eliminate the consult codes, which further meaningfully compromises subspecialty payment. Finally, practicing physicians have not been at the table of health care reform but rather they have been on the menu. There is a considerable difference between the 2 positions in terms of who orders from the menu and who is consumed.

Adalimumab Drug Level in Breast Milk - Uncorrected Proof

2009-12-14

The safety of the anti tumor necrosis factor (TNF)-α antibody adalimumab in nursing mothers is unknown, and studies of its excretion into breast milk are lacking. We report a 26-year-old woman with Cohn's ileitis of 7 years duration. The patient conceived while in remission induced by adalimumab which was started 8 months earlier. Adalimumab was discontinued at week 30 of gestation, and she gave birth to a healthy infant by vaginal delivery on the thirty-eighth week. Four weeks after delivery, the patient experienced a flare-up of disease. Following consultation, she expressed her wish to continue breast feeding after testing for adalimumab presence in the milk. Thereafter, blood and breast milk samples were obtained before, and every 2 days for 8 days after initiation of adalimumab at 40 mg subcutaneously. Sample collection was stopped on day 8, as the patient and her husband then decided not to resume breast feeding of the infant regardless of the results. Breast milk samples were also obtained from 8 healthy nursing mothers as negative controls. Adalimumab levels in serum and breast milk were measured by a specifically developed enzyme-linked immunosorbent assay (ELISA) using plated TNF-α to capture adalimumab, and horseradish peroxidase (HRP) goat anti-human fetal calf (FC) fragment antibody as the detection antibody. The study was approved by the institutional ethics committee of the Sheba Medical Center and all donors provided written informed consent.