Physician adherence to societal guidelines following colonoscopy with polypectomy.

BACKGROUND: Colorectal cancer is a significant cause of mortality and morbidity in western countries. Polypectomy reduces the incidence and mortality of colorectal cancer. Following polypectomy, recommendations regarding the frequency and duration of surveillance rely mostly on features of the resected polyps and are summarized in various gastroenterological societal guidelines. In this study, we aimed to delineate the accuracy of current post-polypectomy surveillance recommendations and to check whether active intervention would lead to an improvement in accuracy and consistency with societal guidelines. METHODS: We prospectively collected polypectomy reports over a 3-month period in 2 tertiary medical centers. We then performed an intervention that included: 1) presentation of results from 1st phase; 2) re-affirming the guidelines in a departmental meeting; 3) addition of a dedicated reporting form for post-polypectomy surveillance recommendations in the patients' electronic medical file. Finally, we conducted a second prospective collection of post-polypectomy recommendations, over a second 3-month period. RESULTS: Prior to the intervention, 76% of the colonoscopies with polypectomy had a recommendation for surveillance, compared to 85% after the intervention (P=0.003). Prior to the intervention, 65% of patients received a recommendation consistent with societal guidelines, compared with 78% after the intervention (P=0.001). CONCLUSION: Intervention, including re-affirmation of the current guidelines and creation of a dedicated reporting platform, significantly increases the number of follow-up recommendations after polypectomy and their consistency with societal guidelines.

Histomorphometric Findings May Help Predicting Response in Patients with Chronic Liver Disease.

BACKGROUND: Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Several viral and host factors related to viral response have been reported in the era of treatment with pegylated (PEG)-interferon and ribavirin. OBJECTIVES: To quantify histological findings from patients with chronic HCV using computerized morphometry and to investigate whether the results can predict response to medical treatment with peg-interferon and ribavirin. METHODS: We followed 58 patients with chronic HCV infection with METAVIR score F1 and F2 in our liver unit who were grouped according to treatment response sustained viral response (SVR) and non-SVR. Liver needle biopsies from these patients were evaluated and histological variables, such as inflammatory cells, collagen fibers and liver architecture, were quantified using computerized morphometrics. The pathologist who performed the histomorphometric analysis was blinded to previous patient clinical and histological information. RESULTS: Histomorphometric variables including the density of collagen fibers were collected. The number of inflammatory cells in the portal space and textural variable were found to be statistically significant and could be used together in a formula to predict response to treatment, with a sensitivity of 93% and a 100% specificity. CONCLUSIONS: Histomorphometry may help to predict a patient's response to treatment at an early stage.

Eosinophilic Esophagitis in Adults: A Concise Overview of an Evolving Disease.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease that encompasses esophageal symptoms along with eosinophilic infiltration of the esophageal epithelium. EoE is an evolving disease that has been a subject of interest to many researchers since the first studies recognized this condition as a new and distinct clinicopathological entity 25 years ago. Clinical presentation in adult patients may include dysphagia, food impaction, vomiting, and reflux symptoms. The diagnosis of EoE is based on the combination of clinical history suggestive of esophageal dysfunction, endoscopic features indicative of the disease, and histology revealing eosinophilic infiltration of the esophageal epithelium that persists after a trial of proton pump inhibitor therapy along with the exclusion of other disorders that may be associated with esophageal tissue eosinophilia. The interplay between EoE and gastroesophageal reflux disease (GERD) is complex, and differentiating these two conditions continues to be difficult and challenging in clinical practice. The mainstay treatment includes dietary modification, topical steroids, and/or endoscopic dilation. The primary care physician (PCP) plays an important role in improving patient care and quality of life by ensuring early referral and participating in management and follow-up. This article provides an overview of the current knowledge base regarding the disease including epidemiology, genetics, pathogenesis, common clinical presentations, the interplay between EoE and GERD, diagnostic approaches, and therapeutic options available to the PCP.

Chronic Constipation in the Elderly Patient: Updates in Evaluation and Management.

Chronic constipation (CC) is a common disorder in the elderly population globally and is associated with comorbidities and negative implications on the quality of life. Constipation prevalence varies in different studies, primarily owing to the nonuniformity of the diagnostic criteria. However, 15%-30% of individuals aged >60 years are diagnosed with CC. Primary care physicians are the main healthcare providers that manage constipation in elderly patients in parallel with increased population aging and increased prevalence of constipation. Physical inactivity, polypharmacy, chronic medical conditions, rectal hyposensitivity, and defecatory disorders all play a role in the pathogenesis of CC in elderly patients. Detailed anamnesis, particularly history related to chronic medication use, with digital rectal examination may assist in identifying constipation causes. Additionally, blood tests and colonoscopy may identify organic causes of CC. Physiologic tests (i.e., anorectal manometry, colonic transit time with radiopaque markers, and defecography) can evaluate the physiologic function of the colon, rectum, and anus. However, generally, there are several causes of constipation in older patients, and an individualized approach is recommended. Treatment of chronic idiopathic constipation is empiric, based on the stepwise approach. Lifestyle advice, adjustment of chronic medications, and prescription of laxatives are the first steps of management. Several laxatives are available, and the treatment is evolving in the last decade. Biofeedback is an effective therapy especially for defecatory disorders. This review aimed to summarize the most updated knowledge for primary care physicians in the approach and management of CC in elderly patients.

Practical clinical approach to the evaluation of hepatobiliary disorders in inflammatory bowel disease.

Hepatobiliary disorders are frequent extraintestinal manifestations in inflammatory bowel disease (IBD) and may appear at any time point during the natural course of the disease. Conceptually, these manifestations can be categorised as: (1) disorders that have an association with IBD; (2) diseases directly and structurally related to intestinal inflammation; (3) diseases related to the adverse effects of IBD treatment; and (4) disorders stemming from the metabolic derangements caused by IBD. The clinical presentations of these disorders range from a mild transient elevation of liver enzymes to liver failure and death. Given this wide differential diagnosis and spectrum of severity, it is understandable that the evaluation of patients with IBD with a hepatobiliary abnormality is often challenging. In this review, we present a concise summary of the common hepatic manifestations seen in patients with IBD and focus on the relevant practical issues encountered by gastroenterologists caring for patients with IBD. A practical clinical approach to the evaluation of liver enzyme abnormalities in patients with IBD is provided based on the predominant enzyme elevation pattern (hepatocellular vs cholestatic), before presenting a working scheme for the prevention of hepatitis B virus (HBV) reactivation in patients with IBD receiving immunosuppressive medications. Finally, we specify several laboratory alterations seen in patients with IBD that can potentially interfere with the interpretation of liver function tests, before defining the specific circumstances when a referral for a hepatological consultation is required for further assessment.

Long-term Follow-up of Severe Eosinophilic Hepatitis: A Rare Presentation of Hypereosinophilic Syndrome.

Idiopathic hypereosinophilic syndrome (HES) is a rare, heterogeneous disorder characterized by a strikingly high eosinophil count (>1,500 cells/µL), over a long period of time (>6 months), with end organ damage. We present a 60-year-old patient with idiopathic HES with isolated liver involvement, a rare systemic disease and a rare solid organ involvement. The patient had a thorough investigational work up until HES was established, including liver biopsy. He needed intensive immunosuppressive treatment at first with steroids, then with azathioprine in conjunction with a low dose of steroids. After 16 years of follow-up, the patient showed no evidence of liver dysfunction. To the best of our knowledge, this is the longest follow-up for a patient with HES-associated chronic hepatitis. Our observation suggests that, with appropriate treatment, liver involvement in HES may be well controlled without deterioration to advanced liver failure.

Eplerenone potentiates the antiproteinuric effects of enalapril in experimental nephrotic syndrome.

Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria and edema. It is believed that nephrin and podocin are involved in the development of proteinuria. The proteinuria and effects of eplerenone alone or combined with enalapril on nephrin/podocin abundance in rats with NS have not yet been studied. Therefore, the present study was designed to examine the early (beginning 2 days before NS induction) and late (beginning 2 wk after NS induction) effects of eplerenone and enalapril, alone or combined, on proteinuria and nephrin/podocin abundance in rats with adriamycin-induced NS. Adriamycin caused a significant increase in daily protein excretion (U(pr)V; from 26.96 +/- 3.43 to 958.57 +/- 56.7 mg/day, P < 0.001) and cumulative proteinuria [from 900.33 +/- 135.5 to 22,490.62 +/- 931.26 mg (P < 0.001)] during 6 wk. Early treatment with enalapril significantly decreased U(pr)V from 958.6 +/- 56.7 to 600.31 +/- 65.13 mg/day (P < 0.001) and cumulative proteinuria to 12,842.37 +/- 1,798.17 mg/6 wk (P < 0.001). Similarly, early treatment with eplerenone produced a profound antiproteinuric effect: U(pr)V decreased from 958.57 +/- 56.7 to 593.38 +/- 21.83 mg/day, P < 0.001, and cumulative proteinuria to 16,601.84 +/- 1,334.31 mg/6 wk; P < 0.001. An additive effect was obtained when enalapril and eplerenone were combined: U(pr)V decreased from 958.57 +/- 56.69 to 424.17 +/- 38.54 mg/day, P < 0.001, and cumulative protein excretion declined to 10,252.88 +/- 1,011.3 mg/6 wk, P < 0.001. These antiproteinuric effects were associated with substantial preservation of glomerular nephrin and podocin. In contrast, late treatment with either enalapril or eplerenone alone or combined mildly decreased U(pr)V and cumulative proteinuria. Thus pretreatment with eplerenone or enalapril is effective in reducing daily and cumulative protein excretion and preservation of nephrin/podocin. More profound antiproteinuric effects were obtained when enalapril and eplerenone were combined.

Glomerular abundance of nephrin and podocin in experimental nephrotic syndrome: different effects of antiproteinuric therapies.

Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria, hypoalbuminemia, and eventual edema formation. Although the mechanisms underlying this phenomenon are not yet fully clarified, it is well accepted that nephrin and podocin are involved in the development of proteinuria. The effects of early treatment with various antiproteinuric therapies on proteinuria and glomerular staining of nephrin and podocin in rats with experimental NS have not been previously studied. Proteinuria and glomerular nephrin and podocin immunofluorescence were examined in rat kidneys with adriamycin-induced NS and the effects of antiproteinuric drug therapies during 5 wk with enalapril, losartan, alone or in combination, omapatrilat, and mycophenolate mofetil on these parameters were assessed. Injection of adriamycin caused a significant increase in daily (from 21.8 +/- 1.4 to 983.1 +/- 45.8 mg/day, P < 0.01) and cumulative protein excretion (from negligible values to 22,490 +/- 931 mg, P < 0.001) during 5 wk. Early treatment with enalapril significantly decreased the daily (641.7 +/- 82.4 mg/day, P < 0.0023) and cumulative proteinuria (15,727 +/- 2,204 mg, P < 0.001). A similar effect, although to a lesser extent, was obtained after omapatrilat treatment: cumulative proteinuria was reduced to 18,706 +/- 1,042 mg, P < 0.001. In contrast, losartan treatment did not significantly influence the cumulative proteinuria that remained comparable (20,351 +/- 1,360 mg, P > 0.05) to that observed in untreated NS rats. Unexpectedly, when losartan was given in combination with enalapril, it abolished the beneficial effects of the latter. Pretreatment with mycophenolate mofetil exerted a moderate antiproteinuric effect, which appeared only during the last week of the experimental treatment. Nephrotic rats exhibited severe disruption of slit diaphragm structure as seen by rapid and profound loss of nephrin and podocin. Beneficial effects of enalapril, omapatrilat, and mycophenolate mofetil paralleled the preservation of nephrin, as determined immunohistochemically, and enabled prediction of significant antiproteinuric responses. Enalapril alone or in combination with losartan resulted in significant preservation of podocin. Pretreatment with enalapril, and to a lesser extent omapatrilat, is superior to losartan in reducing proteinuria in NS rats. A combination of ACE inhibitors with ANG II receptor blockers does not provide any advantageous antiproteinuric therapy in these animals. Nephrin loss is an indication of proteinuria in NS and the antiproteinuric effects of ACE inhibitors, vasopeptidase inhibitors, and mycophenolate mofetil attenuate this reduction. Not all the drugs which restore podocin reduce urinary protein in NS.

[Vasopressin V2 receptor antagonists: pharmacological properties and clinical implications].

Vasopressin, or anti-diuretic hormone, is a peptide hormone that plays an important role in the regulation of extracellular volume and its osmolarity. Increased plasma osmolarity and hypovolemia are the principal physiological stimuli for vasopressin release. The biological effects of vasopressin on its target organs are mediated by two receptors: V1 and V2. V2 is localized to renal tissue and its activation leads to upregulation of aquaporin-2 in the collecting duct allowing the reabsorption of large volumes of water. In contrast, V1 is expressed mainly in blood vessel walls, and its activation results in vascoconstriction. Besides the physiological importance of the vasopressin system, it also plays a crucial role in the pathogenesis of various diseases, including congestive heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone secretion. These clinical syndromes are characterized by enhanced plasma levels of vasopressin, which correlate with the severity of the disease and largely contribute to the development of edema and hyponatremia. Great efforts have been invested in attempting to develop selective and long lasting vasopressin antagonists. However, general medicine and particularly nephrology, suffered from the absence of non-peptide vasopressin blockers that could be taken orally. The last few years have witnessed the development of numerous selective vasopressin antagonists with high bioavailability and long half-lives. Administration of these antagonists to patients with congestive heart failure, cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion substantially enhanced free water excretion and moderately increased serum sodium concentrations. No side effects, except for mild increased thirst sensation, were observed. The present review focuses on the recent developments in vasopressin research, with special emphasize on the development of selective non-peptide antagonists and their clinical use.