Rate and Predictors of Interval Esophageal and Gastric Cancers after Esophagogastroduodenoscopy in the United States.

BACKGROUND AND AIMS: In the United States, little is known about the rates of interval upper gastrointestinal (GI) cancer (possibly missed out) after an esophagogastroduodenoscopy (EGD) is performed. Data from non-US studies reported interval cancer rates of 7-26%. We aimed to study the rate and predictors of interval upper GI cancers in the United States. METHODS: Using the random 5% sample of Medicare beneficiaries in the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified patients diagnosed with esophageal or gastric cancer during 2000-2007. EGD performed within 36 months prior to cancer diagnosis was identified using CPT codes. Cancers diagnosed 6-36 months after EGD were defined as interval (vs. detected) cancers. The chi-square test and the multivariate logistic model were used in statistical analysis. RESULTS: Of 751 patients diagnosed with upper GI cancer, 52 patients (6.9%) were diagnosed with interval cancers 6-36 months after EGD. The rate of interval cancers was 5.5% (31/568) for gastroenterologists and 11.5% (21/183) for non-gastroenterologists (p < 0.01). In multivariate logistic regression, EGDs performed by gastroenterologists (vs. non-gastroenterologists: OR 0.46, 95% CI 0.25-0.83) and those in inpatient setting (vs. outpatient: OR 0.53, 95% CI 0.28-0.997) were associated with a lower likelihood of interval cancers. Sensitivity analyses limited to outpatient EGDs or interval cancers 6-30 months after EGDs led to similar results. CONCLUSIONS: The rate of interval cancers after EGD is the same as the rate of colonoscopy among Medicare patients in the United States. EGDs performed by gastroenterologists and in in-patient settings were associated with a lesser likelihood of interval cancers.

Mediastinal extension of pancreatic pseudocyst--a case with review of topic and management guidelines.

Pancreatic pseudocyst is a common complication of acute and chronic pancreatitis. Extension of a pancreatic pseudocyst into the mediastinum is rare. We present a case of a 43-year-old male with a history of pancreatitis, who presented with dysphagia and was found to have a pancreatic pseudocyst. The pseudocyst was extending to the mediastinum and compressing the esophagus. It was successfully drained externally by computed tomography-guided catheter intervention. Depending on the location and size, patients may present with dyspnea, chest pain, palpitations, or dysphagia; sometimes with hemoptysis, acute respiratory compromise, or cardiogenic shock. There are no recommended guidelines for management. Watchful waiting for spontaneous regression, medical therapy, or drainage internally or externally with endoscopic, percutaneous, or open surgical approach are available options. Based on our own experience and literature review of such cases, we present a management strategy that can limit both complications and recurrence rate. This case emphasizes the importance of the possibility of mediastinal extension of a pancreatic pseudocyst and provides reference guidelines to approach the same.

Suboptimal response to ferrous sulfate in iron-deficient patients taking omeprazole.

Iron deficiency anemia is commonly encountered in outpatient practice. Gastric acid is one of the important factors for optimum absorption of iron. Proton pump inhibitors are very commonly prescribed medications. One of the debated effects of proton pump inhibitors is on oral iron absorption. Their effect on absorption of oral iron supplementation in iron-deficient patients has not been studied. At the Cooper Hematology Outpatient office, we reviewed charts of iron-deficient anemic patients who were on omeprazole for the last 4 years. Fifty patients having no apparent ongoing blood loss, having other causes of anemia especially that of chronic diseases ruled out, and on omeprazole while starting ferrous sulfate therapy for iron deficiency were selected for chart review. The iron-study results at the start of oral ferrous sulfate therapy and at 3 months follow-up were compared to evaluate the response of ferrous sulfate. The mean hemoglobin change was 0.8 ± 1.2 g/L. The mean change in ferrtin values was 10.2 ± 7.8 µg/L. Only 16% of the patients had a normal response to hemoglobin levels (rise of >2 g/dL), and only 40% had a normal response to ferritin levels (rise of >20 µg/dL). The average age of patients having a suboptimal response to both hemoglobin and ferritin was significantly higher compared with that of the patients with an optimal response. Omeprazole and possibly all proton pump inhibitors decrease the absorption of oral iron supplementation. Iron-deficient patients taking proton pump inhibitors may have to be treated with high dose iron therapy for a longer duration or with intravenous iron therapy.

Risk of Hepatobiliary-Gastrointestinal Malignancies and Appropriate Cancer Surveillance in Patients With Primary Sclerosing Cholangitis.

Patients with primary sclerosing cholangitis (PSC) are at risk of hepatobiliary and gastrointestinal cancers. Increased risk of cancer is a result of the chronic, progressive fibro-inflammatory state which ultimately results in the destruction of biliary ducts. PSC is often associated with inflammatory bowel disease (IBD). Patients with PSC are at significant risk of cholangiocarcinoma (CCA), gall bladder malignancy and those with IBD are at increased risk of colorectal cancer. It is important to implement cancer surveillance protocols in these patients. The aim of these protocols is the prevention or early detection of cancerous or pre-cancerous lesions. Given that PSC is rare, large prospective studies evaluating the risk of malignancy in these patients are not available. A great deal of uncertainty exists regarding how to best implement cancer surveillance in these patients. About 50% of deaths in PSC patients are due to malignancy and many patients eventually progress to end-stage liver disease and succumb to hepatic failure. In this review, we cover cancer surveillance strategies in PSC patients based on existing literature and expert opinions.

Examining the Rate of Clostridioides (Formerly Clostridium) Difficile Infection Pre- and Post-COVID-19 Pandemic: An Institutional Review.

Background/ Rationale Clostridioides difficile infection (CDI) is transmitted via the fecal-oral route and is implicated in antibiotic-associated colitis. Similar to CDI, patients with coronavirus disease 2019 (COVID-19) require early identification and isolation, appropriate personal protective equipment, and environmental disinfection to prevent further transmission. In light of this similarity between isolation and protective requirements to prevent transmission of these diseases, we aim to investigate whether there was a decrease in the incidence of CDI during the peak periods of the COVID-19 pandemic compared to historical rates. Methods This is a single-center retrospective analysis of the rates of CDI in our institution. COVID-19 time periods were identified from March 2020 to January 2021 and peak periods (with >50 active patients per day) were defined. The non-COVID-19 periods were July 2017 to February 2020. Rates of CDI were also directly compared across the yearly time period. CDI rates were presented in a per 1000 patient days format. Rates were analyzed per year and during the COVID-19 peaks at our institution. Mann-Whitney U test was used to compare rates between two time periods, while differences across multiple time intervals were analyzed using the Kruskal-Wallis test. Results The median (interquartile range [IQR]) of CDI rates of infection per 1000 patient days for the non-COVID time period from July 2017 to February 2020 was 0.34 (0.23-0.45) while COVID time periods had higher 0.44 (0.25-0.51) rates of CDI although this was not statistically significant (p=0.224). However, there was a statistically significant difference (p=0.036) with COVID peak periods having higher rates of CDI 0.49(0.39-0.74) vs 0.34(0.23-0.44). Overall, there was no statistically significant difference in the rates of CDI across years or time periods (p=0.396). Discussion/Conclusion There was no difference in the rates of hospital-acquired CDI between COVID-19 and non-COVID-19 time periods at our institution.

A genetic database can be utilized to identify potential biomarkers for biphenotypic hepatocellular carcinoma-cholangiocarcinoma.

BACKGROUND: Biphenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC) is an uncommon primary liver neoplasm. Due to limitations in radiologic imaging for the diagnosis of this condition, biopsy is a common method for diagnosis, which is invasive and holds potential complications. To identify alternative means for obtaining the diagnosis and assessing the prognosis of this condition, we evaluated biomarkers for biphenotypic HCC-CC using a genetic database. METHODS: To evaluate the genetic associations with each variable we utilized GeneCards(®), The Human Gene Compendium (http://www.genecards.org). The results of our search were entered into the Pathway Interaction Database from the National Cancer Institute (PID-NCI) (http://pid.nci.nih.gov), to generate a biomolecule interaction map. RESULTS: The results of our query yielded 690 genes for HCC, 98 genes for CC and 50 genes for HCC-CC. Genes depicted in this analysis demonstrate the role of hormonal regulation, embryonic development, cell surface adhesion, cytokeratin stability, mucin production, metalloproteinase regulation, Ras signaling, metabolism and apoptosis. Examples of previously described markers included hepatocyte growth factor (HGF), mesenchymal epithelial transition (MET) and Kirsten rat sarcoma viral oncogene homolog (KRAS). Novel markers included phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), GPC3, choline kinase alpha (CHKA), prostaglandin-endoperoxide synthase 2 (PTGS2), telomerase reverse transcriptase (TERT), myeloid cell leukemia 1 (MCL1) and N-acetyltransferase 2 (NAT2). CONCLUSIONS: GeneCards is a useful research tool in the genetic analysis of low frequency malignancies. Utilizing this tool we identified several biomarkers are methods for diagnosing HCC-CC. Finally, utilizing these methods, HCC-CC was found to be predominantly a subtype of CC.

The Acute Physiology and Chronic Health Evaluation IV, a New Scoring System for Predicting Mortality and Complications of Severe Acute Pancreatitis.

OBJECTIVES: Severe acute pancreatitis is associated with significant morbidity/mortality; thus, the ability to predict hospital course is imperative. An updated version of the Acute Physiology and Chronic Health Evaluation II (APACHE), APACHE IV, has recently been validated. Unlike other versions, APACHE IV uses hepatobiliary parameters and accounts for multiple comorbid conditions and sedation. The intention of this study was to examine APACHE IV for predicting mortality and secondary outcomes for pancreatitis in a prospective cohort. In addition, we compared APACHE IV to APACHE II, Bedside Index for Severity in Acute Pancreatitis, and Ranson criterion. METHODS: We prospectively collected physiologic parameters for each scoring system in 266 patients with severe acute pancreatitis from August 2011 to April 2014. Prognostic value of each score was determined using the area under the receiver operating characteristic curve. RESULTS: Among 266 patients, 59% were men, 52% were white, and 36.5% had alcohol-induced pancreatitis. Mortality occurred in 15 (5.6%), and an APACHE IV of 44 or greater predicted mortality in 100% of cases. The receiver operating characteristic curve for APACHE IV was 0.93 (confidence interval [CI], 0.88-0.97); APACHE II, 0.87 (CI, 0.80-0.94); Bedside Index for Severity in Acute Pancreatitis, 0.86 (CI, 0.78-0.94); and Ranson criterion, 0.90 (CI, 0.94-0.96). CONCLUSION: The APACHE IV is a valid means for predicting mortality and disease-related complications in acute pancreatitis.

Evaluation of polypoid lesions in inflammatory bowel disease.

This article discusses patients with inflammatory bowel disease (IBD), a group which is at increased risk for colorectal carcinoma based on extent and duration of their disease. Patients with chronic IBD (at least 8-10 years duration) should be screened with colonoscopy every 1 to 2 years with multiple jumbo biopsies every 10 cm through the entire colon. Patients with sporadic adenomas can be followed after complete polypectomy, whereas patients with adenoma-like dysplasia-associated lesion or mass (DALMs) need increased surveillance. Patients with flat dysplasia or non adenoma-like DALMs are at high risk for progression and should undergo colectomy. The patients who have indeterminate lesions can be differentiated based on the endoscopic, histologic, and molecular features of the lesion. Long-term follow-up is necessary to determine the natural history of these lesions.

Colonic dysplasia and cancer in inflammatory bowel disease.

Extracolonic malignancies are a relatively rare complication of inflammatory bowel disease. In contrast, colorectal cancer remains a major concern for patients with long-standing UC. The best available evidence suggests that patients with long-standing Crohn's colitis are at similar risk for colorectal cancer as those patients with long-standing UC. In patients with UC, the magnitude of this increased risk appears to be greater in patients with more extensive colonic involvement. It appears that the magnitude of this risk increases with increasing duration of disease, at least in UC. Whether this reflects the increased risk of cancer that occurs with the aging process or a separate phenomena distinct to UC is unclear. To date, the methods available to reduce the risk of cancer are less than optimal. Although surgical procedures eliminate the risk, the mental and physical sequelae of these procedures can be substantial. Surveillance with colonoscopic biopsies is likely effective in reducing although not eliminating the risk of colorectal cancer. Efforts to develop chemopreventative agents and improved surveillance methods remain areas of active investigation.

Does the urgency of endoscopic retrograde cholangiopancreatography (ercp)/percutaneous biliary drainage (pbd) impact mortality and disease related complications in ascending cholangitis? (deim-i study).

BACKGROUND: The Tokyo Guidelines have greatly impacted the management of ascending cholangitis. Though ERCP is the favored modality for biliary decompression, no evidence exists for the timing of ERCP. The DEIM-I study set out to determine if the time from patient presentation to biliary decompression impacted in hospital all cause mortality in ascending cholangitis. METHOD: DEIM-I cohort study was a single-blinded and consisted of 250 subjects with moderate to severe ascending cholangitis who underwent ERCP/PBD. Subjects were randomized into quartiles based upon time from presentation until ERCP/PBD. The primary outcome utilized logistic regression to estimate relative risk (RR) of all cause, in hospital mortality with time to procedure as the predictive covariate. Secondary outcomes were analyzed using multivariate logistic regression and included; multiple organ failure (MOF), sepsis, systemic inflammatory response syndrome (SIRS), surgical incidence, hospital readmission and length of stay (LOS). RESULTS: The risk for hospital mortality was significantly less when biliary drainage was performed within 11 h, compared to >42 h (RR 0.34, 95%CI 0.12 to 0.99, p=0.049). Hospital readmission was lower in subjects who underwent biliary decompression less than 11 h, when compared to those greater than 22 h. Subjects who underwent biliary decompression within 21 h had significant higher risk for surgery compared to those 22-42 h. CONCLUSION: The relative risk of all cause in hospital mortality was lower in subjects who underwent biliary decompression in under 11 h compared to greater than 42 h.

Refractory Inflammatory Bowel Disease.

Therapeutic options for refractory colonic inflammation in patients with ulcerative colitis or Crohn's disease have recently been augmented by the introduction of biologic therapies. Intravenous corticosteroids and cyclosporin A remain the standard therapies for severe ulcerative colitis. Monoclonal antibodies directed at tumor necrosis factor alfa (TNF-alpha) have proven to be most efficacious in patients with severe or refractory Crohn's disease. Immunomodulatory therapy with azathioprine, 6-mercaptopurine, or methotrexate has demonstrated efficacy for maintenance of remission in patients with refractory ulcerative colitis or Crohn's disease. The use of experimental biologic agents may be considered for those patients who fail to respond to or remain dependent on corticosteroids. Surgical intervention is indicated for patients with severe colitis who fail to respond to medical therapy or develop life-threatening complications such as perforation or toxic megacolon.

Treatment of fistulizing Crohn's disease.

The primary goals of the clinician in the treatment of fistulizing Crohn's disease (CD) include (1) defining the anatomy of the fistula, (2) draining any associated infectious material, (3) eradicating the fistulous tract through medical or surgical therapies, and (4) preventing recurrence of fistulas. Evaluation and therapeutic decisions require close collaboration between the gastroenterologist and surgeon. Appropriate evaluation should include identification of septic complications, delineation of the fistulous tract including the origin and terminus of the fistula, and determination of the extent of bowel involvement with active CD. Drainage of abscesses and control of septic complications through the placement of drains or setons is essential. Conservative therapy with avoidance of sphincter muscle-cutting procedures is the standard approach. The appropriate approach to asymptomatic patients is uncertain because there are little data to indicate if treatment alters the natural course of disease.

The role of biological therapy in inflammatory bowel disease.

Substantial evidence suggests a central role for TNF-alpha in the pathogenesis of IBD. This molecular observation has been supported by clinical trials with anti-TNF therapies. The most extensively investigated among the various anti-TNF agents is infliximab. Clinical trials to date have demonstrated its efficacy in inducing remission in patients with moderately active, refractory Crohn's disease (CD) and in managing patients with CD complicated by fistulas. One advantage of infliximab is its rapid onset of action. However, as expected with most medications used to treat patients with IBD, the effect of infliximab is of limited duration, with the response lasting 2-3 months in most patients. The efficacy of repeated infusions of infliximab in maintaining remission in patients with inflammatory CD has been demonstrated in one trial to date. The results from the ACCENT I trial should soon be available. Many other important questions regarding the use of infliximab remain unanswered. These include the optimal schedules of infusions, the effect of concomitant therapy with aminosalicylates, immunomodulators and antibiotics, and the timing and indication of using infliximab in the general management algorithm of a patient with CD. Certainly, the efficacy of infliximab in the treatment of ulcerative colitis (UC) remains to be further explored in a controlled fashion, though preliminary uncontrolled data suggests efficacy. As experience with infliximab use accumulates, more data will become available regarding its safety with either short-term or long-term use. A large body of evidence exists regarding the short-term safety of infliximab. The concern of increased risk of hypersensitivity-like reactions with longer interval between treatments will also need to be addressed. The currently available data supports that infliximab is safe and well tolerated. Other anti-TNF therapies will also need to be investigated with the same rigor before widespread use can be advocated. In addition to these agents, advances in molecular engineering techniques have further expanded the array of biologic therapies available to treat IBD. These newer therapies hold promise in targeting specific pathways of the pathogenesis of IBD that may be different from all prior therapies. Certainly, the anti-TNF therapies and others aforementioned have taken the field of IBD into a new and exciting generation, the biological era. (c) 2001 Prous Science. All rights reserved.

Extraintestinal manifestations of inflammatory bowel disease.

Numerous extraintestinal diseases have been associated with IBD. The role of the gastrointestinal tract in host response to the foreign antigens present in the gut makes the enteric immune system highly susceptible to any external perturbation to the system. Dysregulation of the enteric immune response results in pathology in various organs outside of the gut. The site-specific manifestations of this immune response are not understood fully. Better understanding of the pathogenesis of IBD and the complex interactions between the gut immune system and the extraintestinal systems would provide insights into the development of many of these extraintestinal manifestations. Much is unknown about the presence of cardiac, pulmonary, and hematologic diseases in patients with IBD. True association or coincidental presence of the diseases in these organ systems with IBD requires better delineation. An important consideration in all patients with IBD presenting with extraintestinal manifestations should be a careful search for medication-related complications.