Gyanprakash A. Ketwaroo

The risks of thromboembolism vs. recurrent gastrointestinal bleeding after interruption of systemic anticoagulation in hospitalized inpatients with gastrointestinal bleeding: a prospective study

OBJECTIVES:Anticoagulants carry a significant risk of gastrointestinal bleeding (GIB). Data regarding the safety of anticoagulation continuation/cessation after GIB are limited. We sought to determine the safety and risk of continuation of anticoagulation after GIB.METHODS:We conducted a prospective observational cohort study on consecutive patients admitted to the hospital who had GIB while on systemic anticoagulation. Patients were classified into two groups at hospital discharge after GIB: those who resumed anticoagulation and those who had anticoagulation discontinued. Patients in both groups were contacted by phone 90 days after discharge to determine the following outcomes: (i) thromboembolic events, (ii) hospital readmissions related to GIB, and (iii) mortality. Univariate and multivariate Cox proportional hazards were used to determine factors associated with thrombotic events, rebleeding, and death.RESULTS:We identified 197 patients who developed GIB while on systemic anticoagulation (n=145, 74% on warfarin). Following index GIB, anticoagulation was discontinued in 76 patients (39%) at discharge. In-hospital transfusion requirements, need for intensive care unit care, and etiology of GIB were similar between the two groups. During the follow-up period, 7 (4%) patients suffered a thrombotic event and 27 (14%) patients were readmitted for GIB. Anticoagulation continuation was independently associated on multivariate regression with a lower risk of major thrombotic episodes within 90 days (hazard ratio (HR)=0.121, 95% confidence interval (CI)=0.006–0.812, P=0.03). Patients with any malignancy at time of GIB had an increased risk of thromboembolism in follow-up (HR=6.1, 95% CI=1.18–28.3, P=0.03). Anticoagulation continuation at discharge was not significantly associated with an increased risk of recurrent GIB at 90 days (HR=2.17, 95% CI=0.861–6.67, P=0.10) or death within 90 days (HR=0.632, 95% CI=0.216–1.89, P=0.40).CONCLUSIONS:Restarting anticoagulation at discharge after GIB was associated with fewer thromboembolic events without a significantly increased risk of recurrent GIB at 90 days. The benefits of continuing anticoagulation at discharge may outweigh the risks of recurrent GIB.

Opioid-Induced Bowel Dysfunction

Opioid-induced bowel dysfunction (OIBD) is a potentially debilitating side effect of chronic opioid use. It refers to a collection of primarily gastrointestinal motility disorders induced by opioids, of which opioid-induced constipation (OIC) is the most common. Management of OIBD is difficult, and affected patients will often limit their opioid intake at the expense of experiencing more pain, to reduce the negative impact of OIBD on their quality of life. Effective pharmacologic therapy for OIC is considered an unmet need and several agents have recently been given priority review and approval for OIC. Furthermore, multiple agents currently in development show promise in treating OIC without significant impact on analgesia or precipitation of withdrawal symptoms. The approval and availability of such medications would represent a significant improvement in the management of OIC and OIBD in patients with chronic pain.

Defining the Accuracy of Secretin Pancreatic Function Testing in Patients With Suspected Early Chronic Pancreatitis

OBJECTIVES:The diagnosis of chronic pancreatitis in patients with characteristic symptoms but normal pancreatic imaging is challenging. Assessment of pancreatic function through secretin pancreatic function testing (SPFT) has been advocated in this setting, but its diagnostic accuracy is not fully known.METHODS:This was a retrospective review of patients who received SPFT at our tertiary care institution between January 1995 and December 2008 for suspected chronic pancreatitis. For all patients, medical records were reviewed for evidence of subsequent development of chronic pancreatitis by imaging and/or pathology. Patients were then categorized as “true positive” or “true negative” for chronic pancreatitis based on follow-up imaging or histologic evidence.RESULTS:In all, 116 patients underwent SPFT. Of the 27 patients who tested positive, 7 were lost to follow-up. Of the remaining 20 SPFT-positive patients, 9 (45%) developed radiologic or histologic evidence of chronic pancreatitis after a median of 4 years (1–11 years). Of the 89 patients who had negative SPFT testing, 19 were lost to follow-up. Of the remaining 70 patients, 2 were eventually diagnosed with chronic pancreatitis based on subsequent imaging/histology after a median follow-up period of 7 years (3–11 years). The sensitivity of the SPFT in diagnosing chronic pancreatitis was 82% with a specificity of 86%. The positive predictive value (PPV) of chronic pancreatitis was 45% with a negative predictive value (NPV) of 97%.CONCLUSIONS:In patients with suspected early chronic pancreatitis and normal pancreatic imaging, SPFT is highly accurate at ruling out early chronic pancreatitis with a NPV of 97%.

Salvage cryotherapy after failed radiofrequency ablation for Barrett’s esophagus–related dysplasia is safe and effective

BACKGROUND Radiofrequency ablation (RFA) is an effective treatment for Barretts esophagus (BE) dysplasia. For patients with dysplasia refractory to RFA, data are limited regarding efficacy of endoscopic therapy. OBJECTIVE To assess the efficacy and safety of cryotherapy in patients with BE dysplasia who failed RFA. DESIGN Single-center, retrospective, cohort study. SETTING Tertiary-care center between 2006 and 2013. PATIENTS Patients with BE and low-grade dysplasia (LGD), high-grade dysplasia (HGD), or intramucosal carcinoma (IMC) were referred for RFA every 2 to 3 months. Response was determined by complete eradication of dysplasia (CE-D). INTERVENTIONS Patients without CE-D or those with recurrent dysplasia after initial eradication were offered cryotherapy. MAIN OUTCOME MEASUREMENTS Eradication of dysplasia and/or cancer. Secondary outcome, eradication of intestinal metaplasia. RESULTS A total of 121 patients underwent RFA for BE dysplasia (55% HGD, 26% LGD, 17% IMC, 2% indefinite dysplasia). After a median of 3 RFA sessions, 75% (n = 91) had CE-D. Patients without CE-D were more likely to have a longer BE length (7 cm vs 4 cm; P = .004) and a hiatal hernia (83% vs 55%; P = .005). Sixteen patients (14 with failed CE-D and 2 with recurrent dysplasia) were offered cryotherapy and had endoscopic follow-up. Seven (57%) had HGD before cryotherapy (6 with LGD, 2 with IMC, and 1 with indefinite dysplasia). After cryotherapy, 12 (75%) had CE-D, and 5 (31%) had eradication of intestinal metaplasia. Of patients with IMC, 100% had CE-D. Three patients developed strictures that responded to dilation. LIMITATIONS Single center, retrospective nature of study. CONCLUSION For patients with refractory dysplasia or recurrent dysplasia after RFA, salvage cryotherapy is a safe and effective endoscopic therapy.

Approach to patients with suspected chronic pancreatitis: a comprehensive review.

Chronic pancreatitis (CP) represents a significant health care burden in the United States. Diagnosing it early and accurately is important for the efficient management of these patients. However, the early diagnosis of CP, when structural and functional pancreatic changes are subtle, remains difficult. Complicating this is the large cohort of patients with nonspecific abdominal pain who are often suspected of having early CP and who utilize significant health care resources in attempts at diagnosis and management. We present a review of the current diagnostic tests available for making an early diagnosis of CP. We further report our approach to patients suspected of having CP based on the available literature.

Risk Factors for Adverse Outcomes in Patients Hospitalized With Lower Gastrointestinal Bleeding

OBJECTIVE To determine which risk factors and subtypes of lower gastrointestinal bleeding (LGIB) are associated with adverse outcomes after hospital discharge (30-day readmissions, recurrent LGIB, and death). PATIENTS AND METHODS We conducted a prospective observational study of consecutive patients admitted with LGIB to Beth Israel Deaconess Medical Center from April 1, 2013, through March 30, 2014. Patients were contacted 30 days after discharge to determine hospital readmissions, recurrent LGIB, and death. Multivariable Cox proportional hazards regression models were used to describe associations of variables with 30-day readmissions or recurrent LGIB. Logistic regression was used to determine association with mortality. RESULTS There were 277 patients hospitalized with LGIB. Of the 271 patients surviving to discharge, 21% (n=57) were readmitted within 30 days, 21 of whom were admitted for recurrent LGIB. The following factors were associated with 30-day readmissions: developing in-hospital LGIB (hazard ratio [HR], 2.26; 95% CI, 1.08-4.28), anticoagulation (HR, 1.82; 95% CI, 1.05-3.10), and active malignancy (HR, 2.33; 95% CI, 1.11-4.42). Patients discharged while taking anticoagulants had higher rates of recurrent bleeding (HR, 2.93; 95% CI, 1.15-6.95). Patients with higher Charlson Comorbidity Index scores (odds ratio [OR], 1.57; 95% CI, 1.25-2.08), active malignancy (OR, 6.57; 95% CI, 1.28-28.7), and in-hospital LGIB (OR, 11.5; 95% CI, 2.56-52.0) had increased 30-day mortality risk. CONCLUSION In-hospital LGIB, anticoagulation, and active malignancy are risk factors for 30-day readmissions in patients hospitalized with LGIB. In-hospital LGIB, Charlson Comorbidity Index scores, and active malignancy are risk factors for 30-day mortality.

Quality Improvement in Gastroenterology Clinical Practice

An emphasis on quality improvement (QI) is vital to the cost-effective provision of evidence-based health care. QI projects in gastroenterology have typically focused on endoscopy to minimize or eliminate procedure-related complications or errors. However, a significant component of gastroenterology care is based on the management of chronic disease. Patients with chronic diseases are seen in many different outpatient practices in the community and academia. In an attempt to ensure that every patient receives high-quality care, major gastrointestinal societies have published guidelines on the management of common gastrointestinal complaints. However, adherence to these guidelines varies. We discuss common outpatient gastrointestinal illnesses with established guidelines for management that could benefit from active QI projects; these would ensure a consistently high standard of care for every patient.

CFTR dysfunction predisposes to fibrotic liver disease in a murine model

Cystic fibrosis liver disease (CFLD) is a rapidly progressive biliary fibrosis, resembling primary sclerosing cholangitis that develops in 5-10% of patients with cystic fibrosis. Further research and evaluation of therapies are hampered by the lack of a mouse model for CFLD. Although primary sclerosing cholangitis is linked to both ulcerative colitis and loss of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel function, induction of colitis with dextran sodium sulfate (DSS) in cftr(-/-) mice causes bile duct injury but no fibrosis. Since profibrogenic modifier genes are linked to CFLD, we examined whether subthreshhold doses of the profibrogenic xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), along with DSS-induced colitis, lead to bile duct injury and liver fibrosis in mice that harbor loss of CFTR function. Exon 10 heterozygous (cftr(+/-)) and homozygous (cftr(-/-)) mice treated with DDC demonstrated extensive mononuclear cell inflammation, bile duct proliferation, and periductular fibrosis. In contrast, wild-type (cftr(+/+)) littermates did not develop bile duct injury or fibrosis. Histological changes corresponded to increased levels of alkaline phosphatase, hydroxyproline, and expression of profibrogenic transcripts for transforming growth factor-β(1), transforming growth factor-β(2), procollagen α(1)(I), and tissue inhibitor of matrix metaloproteinase-1. Immunohistochemistry demonstrated fibrosis and activation of periductal fibrogenic cells based on positive staining for lysyl oxidase-like-2, α-smooth muscle actin, and collagen I. These data demonstrate that subthreshold doses of DDC, in conjunction with DSS-induced colitis, results in bile duct injury and periductal fibrosis in mice with partial or complete loss of CFTR function and may represent a useful model to study the pathogenic mechanisms by which CFTR dysfunction predisposes to fibrotic liver disease and potential therapies.

Pancreatic Cystic Neoplasms : An Update

The incidence of pancreatic cystic neoplasms is rising, in part from detection through the increasing use of high-resolution cross-sectional imaging techniques. Initial diagnosis is generally based on imaging characteristics identified on computed tomography and/or MRI. Endoscopic ultrasound provides further imaging characterization and also enables fluid aspiration and analysis to additionally aid differentiation. The general approach to these lesions includes surgical intervention and/or surveillance imaging. Taking into account diverse presentations, varying malignant potential, and the uncertain natural history of some of these lesions, an evidence-based approach is limited. This article discusses recent updates in the diagnosis and management of cystic neoplasms of the pancreas.

Localizing Acute Lower Gastrointestinal Hemorrhage: CT Angiography Versus Tagged RBC Scintigraphy

OBJECTIVE Lower gastrointestinal hemorrhage is a common cause of hospitalization and has substantial associated morbidity and financial cost. CT angiography (CTA) is emerging as an alternative to (99m)Tc-labeled RBC scintigraphy (RBC scintigraphy) for the localization of acute lower gastrointestinal bleeding (LGIB); however, data on comparative efficacy are scant. The aim of this study was to assess the utility of CTA compared with RBC scintigraphy in the overall evaluation and management of acute LGIB. MATERIALS AND METHODS We retrospectively reviewed images from all CTA examinations performed for suspected acute LGIB at our tertiary care hospital from January 2010 through November 2011. The comparison group was determined by retrospective review of twice the number of RBC scintigraphic scans consecutively obtained from June 2008 to November 2011 for the same indication. All CTA and RBC scintigraphic scans were reviewed for accurate localization of the site and source of suspected active LGIB. RESULTS In total, 45 CTA and 90 RBC scintigraphic examinations were performed during the study period. Seventeen (38%) CTA scans showed active gastrointestinal bleeding compared with 34 (38%) RBC scintigraphic scans (p = 1.000). However, the site of bleeding was accurately localized on 24 (53%) CTA scans. This proportion was significantly greater than the proportion localized on RBC scintigraphic scans (27 [30%]) (p = 0.008). There were no significant differences between the two groups in average hospital length of stay, blood transfusion requirement, incidence of acute kidney injury, or in-hospital mortality. CONCLUSION Both CTA and RBC scintigraphy can be used to identify active bleeding in 38% of cases. However, the site of bleeding is localized with CTA in a significantly higher proportion of studies.