Microscopic colitis - review

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenMicroscopic colitis (MC) is an encompassing term for two diseases; collagenous colitis and lymphocytic colitis. The colon appears normal by colonoscopy and a diagnosis is only obtained with a biopsy. The histopathology of collagenous colitis is mainly characterized by a thickening of the subepithelial basement membrane of the colonic mucosa with a band of collagen. Lymphocytic colitis is mainly characterized by an intraepithelial lymphocytosis without the collagen thickening. Even though the two diseases have a distinctive pathology their clinical symptoms are characterized by chronic watery diarrhea without bleeding. Microscopic colitis is thought to cause about 4-13% of all chronic diarrhea but their relative frequency is much higher among older people. The mean annual incidence for collagenous and lymphocytic colitis has been increasing. Steroids are the most effective treatment for microscopic colitis and budesonide is the most studied and effective therapy for MC. The aim of this paper is to give a review of two relatively new diseases which are among the most common cause of chronic diarrhea, especially among older people.Hugtakið smásæ ristilbólga er samnefnari fyrir tvo sjúkdóma; bandvefsristilbólgu og eitilfrumu-ristilbólgu. Við ristilspeglun er slímhúðin eðlileg en greining fæst með sýnatöku á ristilslímhúð. Meinafræðilega einkennist bandvefsristilbólga einkum af þykknuðu kollagenlagi undir yfirborðsþekju slímhúðar ristilsins en eitilfrumuristilbólga af eitilfrumuíferð í yfirborðsþekju, kirtilþekju og eiginþynnu slímhúðar án aukningar á kollageni í ristilslímhúðinni. Þó að sjúkdómarnir tveir hafi nokkuð aðgreinanlegt meinafræðilegt mynstur er megineinkenni þeirra beggja langvinnur vatnskenndur niðurgangur án blóðs. Smásæ ristilbólga er talin orsaka um 4-13% langvinns niðurgangs en algengi hennar er mun hærra meðal eldra fólks. Nýgengi bandvefsristilbólgu og eitilfrumuristilbólgu hefur farið mjög hækkandi á síðustu árum. Steralyf eru áhrifaríkustu lyfin við smásærri ristilbólgu og búdesóníð er mest rannsakaða og best staðfesta meðferðin. Tilgangur þessarar yfirlitsgreinar er að kynna tvo tiltölulega nýja sjúkdóma sem eru ein algengasta ástæða langvinns niðurgangs, sérstaklega meðal eldra fólks

Effects of truck traffic on top-down fatigue cracking performance of flexible pavements using a new mechanics-based analysis framework

The mechanics-based analysis framework predicts top-down fatigue cracking initiation time in asphalt concrete pavements by utilising fracture mechanics and mixture morphology-based property. To reduce the level of complexity involved, traffic data were characterised and incorporated into the framework using the equivalent single axle load (ESAL) approach. There is a concern that this kind of simplistic traffic characterisation might result in erroneous performance predictions and pavement structural designs. This paper integrates axle load spectra and other traffic characterisation parameters into the mechanics-based analysis framework and studies the impact these traffic characterisation parameters have on predicted fatigue cracking performance. The traffic characterisation inputs studied are traffic growth rate, axle load spectra, lateral wheel wander and volume adjustment factors. For this purpose, a traffic integration approach which incorporates Monte Carlo simulation and representative traffic characterisation inputs was developed. The significance of these traffic characterisation parameters was established by evaluating a number of field pavement sections. It is evident from the results that all the traffic characterisation parameters except truck wheel wander have been observed to have significant influence on predicted top-down fatigue cracking performance

Validation of podocalyxin-like protein as a biomarker of poor prognosis in colorectal cancer

Background: Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and adverse outcome in several cancer types. We recently demonstrated that overexpression of PODXL is an independent factor of poor prognosis in colorectal cancer (CRC). The aim of this study was to validate these results in two additional independent patient cohorts and to examine the correlation between PODXL mRNA and protein levels in a subset of tumours. Method: PODXL protein expression was analyzed by immunohistochemistry in tissue microarrays with tumour samples from a consecutive, retrospective cohort of 270 CRC patients (cohort 1) and a prospective cohort of 337 CRC patients (cohort 2). The expression of PODXL mRNA was measured by real-time quantitative PCR in a subgroup of 62 patients from cohort 2. Spearman's Rho and Chi-Square tests were used for analysis of correlations between PODXL expression and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modelling were applied to assess the relationship between PODXL expression and time to recurrence (TTR), disease free survival (DFS) and overall survival (OS). Results: High PODXL protein expression was significantly associated with unfavourable clinicopathological characteristics in both cohorts. In cohort 1, high PODXL expression was associated with a significantly shorter 5-year OS in both univariable (HR = 2.28; 95% CI 1.43-3.63, p = 0.001) and multivariable analysis (HR = 2.07; 95% CI 1.25-3.43, p = 0.005). In cohort 2, high PODXL expression was associated with a shorter TTR (HR = 2.93; 95% CI 1.26-6.82, p = 0.013) and DFS (HR = 2.44; 95% CI 1.32-4.54, p = 0.005), remaining significant in multivariable analysis, HR = 2.50; 95% CI 1.05-5.96, p = 0.038 for TTR and HR = 2.11; 95% CI 1.13-3.94, p = 0.019 for DFS. No significant correlation could be found between mRNA levels and protein expression of PODXL and there was no association between mRNA levels and clinicopathological parameters or survival. Conclusions: Here, we have validated the previously demonstrated association between immunohistochemical expression of PODXL and poor prognosis in CRC in two additional independent patient cohorts. The results further underline the potential utility of PODXL as a biomarker for more precise prognostication and treatment stratification of CRC patients

Survival trends in patients diagnosed with colon and rectal cancer in the nordic countries 1990-2016 : The NORDCAN survival studies

Background: Survival of patients with colon and rectal cancer has improved in all Nordic countries during the past decades. The aim of this study was to further assess survival trends in patients with colon and rectal cancer in the Nordic countries by age at diagnosis and to present additional survival measures. Methods: Data on colon and rectal cancer cases diagnosed in the Nordic countries between 1990 and 2016 were obtained from the NORDCAN database. Relative survival was estimated using flexible parametric models. Both age-standardized and age-specific measures for women and men were estimated from the models, as well as reference-adjusted crude probabilities of death and life-years lost. Results: The five-year age-standardized relative survival of colon and rectal cancer patients continued to improve for women and men in all Nordic countries, from around 50% in 1990 to about 70% at the end of the study period. In general, survival was similar across age and sex. The largest improvement was seen for Danish men and women with rectal cancer, from 41% to 69% and from 43% to 71%, respectively. The age-standardized and reference-adjusted five-year crude probability of death in colon cancer ranged from 30% to 36% across countries, and for rectal cancer from 20% to 33%. The average number of age-standardized and reference-adjusted life-years lost ranged between six and nine years. Conclusion: There were substantial improvements in colon and rectal cancer survival in all Nordic countries 1990-2016. Of special note is that the previously observed survival disadvantage in Denmark is no longer present. (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe

Cracking in asphalt materials

This chapter provides a comprehensive review of both laboratory characterization and modelling of bulk material fracture in asphalt mixtures. For the purpose of organization, this chapter is divided into a section on laboratory tests and a section on models. The laboratory characterization section is further subdivided on the basis of predominant loading conditions (monotonic vs. cyclic). The section on constitutive models is subdivided into two sections, the first one containing fracture mechanics based models for crack initiation and propagation that do not include material degradation due to cyclic loading conditions. The second section discusses phenomenological models that have been developed for crack growth through the use of dissipated energy and damage accumulation concepts. These latter models have the capability to simulate degradation of material capacity upon exceeding a threshold number of loading cycles.Peer ReviewedPostprint (author's final draft

2010 SSO John Wayne Clinical Research Lecture: Rectal Cancer Outcome Improvements in Europe: Population-Based Outcome Registrations will Conquer the World

During the past two decades, rectal cancer treatment has improved considerably in Europe. Clinical trials played a crucial role in improving surgical techniques, (neo)adjuvant treatment schedules, imaging, and pathology. However, there is still a wide variation in outcome after rectal cancer. In most western health care systems, efforts are made to reduce hospital variation by focusing on selective referral and encouraging patients to seek care in high-volume hospitals. On the other hand, the expertise for diagnosis and treatment of common types of cancer should be preferably widespread and easily accessible for all patients. As an alternative to volume-based referral, hospitals and surgeons can improve their results by learning from their own outcome statistics and those from colleagues treating a similar patient group. Several European surgical (colo)rectal audits have led to improvements with a greater impact than any of the adjuvant therapies currently under study. However, differences remain between European countries, which cannot be easily explained. To generate the best care for colorectal cancer in the whole of Europe and to meet political and public demands for transparency, the European CanCer Organisation (ECCO) initiated an international, multidisciplinary, outcome-based quality improvement program: European Registration of Cancer Care (EURECCA). The goal is to create a multidisciplinary European registration structure for patient, tumor, and treatment characteristics linked to outcome registration. Clinical trials will always play a major role in improving rectal cancer treatment. To further improve outcomes and diminish variation, EURECCA will establish the basis for a strong, multidisciplinary, international audit structure that can be used as a template for similar projects worldwide

High expression of tumour-associated trypsin inhibitor correlates with liver metastasis and poor prognosis in colorectal cancer

Increased expression of tumour-associated trypsin inhibitor (TATI) in tumour tissue and/or serum has been associated with poor survival in various cancer forms. Moreover, a proinvasive function of TATI has been shown in colon cancer cell lines. In this study, we have examined the prognostic significance of tumour-specific TATI expression in colorectal cancer, assessed by immunohistochemistry (IHC) on tissue microarrays (TMAs) with tumour specimens from two independent patient cohorts. Kaplan–Meier analysis and Cox proportional hazards modelling were used to estimate time to recurrence, disease-free survival and overall survival. In both cohorts, a high (>50% of tumour cells) TATI expression was an independent predictor of a significantly shorter overall survival. In cohort II, in multivariate analysis including age, gender, disease stage, differentiation grade, vascular invasion and carcinoembryonal antigen (CEA), high TATI expression was associated with a significantly decreased overall survival (HR=1.82; 95% CI=1.19–2.79) and disease-free survival (HR=1.56; 95% CI=1.05–2.32) in curatively treated patients. Moreover, there was an increased risk for liver metastasis in both cohorts that remained significant in multivariate analysis in cohort II (HR=2.85; 95% CI=1.43–5.66). In conclusion, high TATI expression is associated with liver metastasis and is an independent predictor of poor prognosis in patients with colorectal cancer

A Controversy That Has Been Tough to Swallow: Is the Treatment of Achalasia Now Digested?

Esophageal achalasia is a rare neurodegenerative disease of the esophagus and the lower esophageal sphincter that presents within a spectrum of disease severity related to progressive pathological changes, most commonly resulting in dysphagia. The pathophysiology of achalasia is still incompletely understood, but recent evidence suggests that degeneration of the postganglionic inhibitory nerves of the myenteric plexus could be due to an infectious or autoimmune mechanism, and nitric oxide is the neurotransmitter affected. Current treatment of achalasia is directed at palliation of symptoms. Therapies include pharmacological therapy, endoscopic injection of botulinum toxin, endoscopic dilation, and surgery. Until the late 1980s, endoscopic dilation was the first line of therapy. The advent of safe and effective minimally invasive surgical techniques in the early 1990s paved the way for the introduction of laparoscopic myotomy. This review will discuss the most up-to-date information regarding the pathophysiology, diagnosis, and treatment of achalasia, including a historical perspective. The laparoscopic Heller myotomy with partial fundoplication performed at an experienced center is currently the first line of therapy because it offers a low complication rate, the most durable symptom relief, and the lowest incidence of postoperative gastroesophageal reflux