Are ulcers a marker for invasive carcinoma in barrett's esophagus? data from a diagnostic variability study with clinical follow-up

We correlated follow-up information from 138 patients with Barrett's esophagus and varying degrees of dysplasia with the presence of ulcers. Methods A group of pathologist participants were asked to contribute patients’ initial biopsy slides showing Barrett's esophagus (BE) without dysplasia and with epithelial changes indefinite for dysplasia, low grade dysplasia (LGD), high grade dysplasia (HGD), and adenocarcinoma. From the initial 250 cases used for a diagnostic reproducibility study, follow-up information was available for 138 patients. Results There were 44 cases submitted as BE, 22 as BE with epithelial changes indefinite for dysplasia, 26 as BE with LGD, 33 as BE with HGD, and 13 as BE with adenocarcinoma. Ulcers were present in 35/138 cases (25%), including 3/44 cases of BE without dysplasia (7%), 2/22 cases of BE with epithelial changes indefinite for dysplasia (9%), 0/26 cases of BE with LGD (0%), 10/33 cases of BE with HGD (30%), and 7/13 cases of BE with adenocarcinoma (54%). On follow-up, there were no invasive carcinomas detected among the BE without dysplasia group (median follow-up = 38.5 months). Adenocarcinomas were detected in 4/22 cases (18%) submitted as BE with epithelial changes indefinite for dysplasia at 19, 55, 60, and 62 months and in 4/26 cases (15%) of BE with LGD at 9, 9, 11, and 60 months. None of these carcinomas occurred in cases in which an ulcer was present in the initial biopsy specimen. Among the 33 HGD cases, 20 (60%) were found to have adenocarcinoma on subsequent resection specimens. The presence of an ulcer with HGD increased the likelihood of finding carcinoma in the resection specimen, as 8/10 biopsies (80%) of HGD patients with ulcers had carcinoma, compared to 12/23 biopsies (52%) of HGD patients without ulcers. All of the cases interpreted as adenocarcinomas on biopsy were found either to have invasive carcinoma on esophageal resection or to have metastases that were demonstrated in unresectable patients. Conclusion If an ulcer accompanies HGD in a biopsy specimen from a patient with BE, it is likely that invasive carcinoma is also present at that time.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75186/1/j.1572-0241.2002.05420.x.pd

Proteomics analysis reveals a Th17-prone cell population in presymptomatic graft-versus-host disease

Gastrointestinal graft-versus-host-disease (GI-GVHD) is a life-threatening complication occurring after allogeneic hematopoietic cell transplantation (HCT), and a blood biomarker that permits stratification of HCT patients according to their risk of developing GI-GVHD would greatly aid treatment planning. Through in-depth, large-scale proteomic profiling of presymptomatic samples, we identified a T cell population expressing both CD146, a cell adhesion molecule, and CCR5, a chemokine receptor that is upregulated as early as 14 days after transplantation in patients who develop GI-GVHD. The CD4+CD146+CCR5+ T cell population is Th17 prone and increased by ICOS stimulation. shRNA knockdown of CD146 in T cells reduced their transmigration through endothelial cells, and maraviroc, a CCR5 inhibitor, reduced chemotaxis of the CD4+CD146+CCR5+ T cell population toward CCL14. Mice that received CD146 shRNA-transduced human T cells did not lose weight, showed better survival, and had fewer CD4+CD146+CCR5+ T cells and less pathogenic Th17 infiltration in the intestine, even compared with mice receiving maraviroc with control shRNA- transduced human T cells. Furthermore, the frequency of CD4+CD146+CCR5+ Tregs was increased in GI-GVHD patients, and these cells showed increased plasticity toward Th17 upon ICOS stimulation. Our findings can be applied to early risk stratification, as well as specific preventative therapeutic strategies following HCT

Never the twain shall meet: a critical appraisal of the combination of discourse and psychoanalytic theory in studies of men and masculinity

In recent years there has been a number of attempts by different researchers to study men and masculinity using a combination of discourse theory and psychoanalysis. The main reason for this development is the sense that, on its own, discourse theory provides an incomplete account of masculine subjectivity. Psychoanalysis is thought to be able to fill those gaps. In this paper I want to begin by reviewing these arguments. I will provide an outline of the alleged deficiencies in discursive approaches to men and masculinity before going on to examine some of the work that has attempted the above synthesis. What I aim to show is that, for a number of reasons, such attempts are bound to fail. Instead, I will argue that better progress can be made in studies of masculinity by remaining within the theoretical boundaries of Discursive Psychology

A multi‐institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99090/1/cncr28117.pd

A theory led narrative review of one-to-one health interventions:the influence of attachment style and client-provider relationship on client adherence

A theory-led narrative approach was used to unpack the complexities of the factors that enable successful client adherence following one-to-one health interventions. Understanding this could prepare the provider to anticipate different adherence behaviours by clients, allowing them to tailor their interventions to increase the likelihood of adherence. The review was done in two stages. A theoretical formulation was proposed to explore factors which influence the effectiveness of one-to-one interventions to result in client adherence. The second stage tested this theory using a narrative synthesis approach. Eleven studies across the health care arena were included in the synthesis and explored the interplay between client attachment style, client–provider interaction and client adherence with health interventions. It emerged that adherence results substantially because of the relationship that the client has with the provider, which is amplified or diminished by the client’s own attachment style. This occurs because the client’s attachment style shapes how they perceive and behave in relationships with the health-care providers, who become the ‘secure base’ from which the client accepts, assimilates and adheres with the recommended health intervention. The pathway from one-to-one interventions to adherence is explained using moderated mediation and mediated moderation models

Negative expectations of treatment: Some ideas about the source and management of two types

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44352/1/10615_2005_Article_BF01786039.pd

An Application of the Concept of the Therapeutic Alliance To Sadomasochistic Pathology

This paper traces the history of the therapeutic alliance concept, examining how it has been used and misused, at times elevated to a central position and at others rejected altogether. The loss of this concept created a vacuum in classical psychoanalysis that has been filled by rival theories. The continuing usefulness of looking at the treatment process through the lens of the therapeutic alliance, particularly in relation to the manifold difficulties of working with sadomasochistic pathology, is suggested. To this end, revisions of the theory of the therapeutic alliance are suggested to address some of the difficulties that have arisen in conceptualizing this aspect of the therapeutic relationship, and to provide an integrated dynamic model for working with patients at each phase of treatment. This revised model acknowledges the complexity of the domain and encompasses the multiple tasks, functions, partners, and treatment phases involved. The utility of the revised theory is illustrated in application to understanding the sadomasochistic, omnipotent resistances of a female patient through the phases of her analysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66889/2/10.1177_00030651980460031301.pd

The frequency of microscopic and focal active colitis in patients with irritable bowel syndrome

<p>Abstract</p> <p>Background</p> <p>Irritable bowel syndrome (IBS) is a chronic functional bowel disorder. The frequency of microscopic colitis and focal active colitis in the colonic mucosa has been investigated in IBS patients.</p> <p>Methods</p> <p>Between June 2007 and September 2010, 378 patients (between 16 and 84 years) were recruited prospectively. Of these 378 patients, 226 patients were diagnosed with IBS using the Rome III criteria. 152 control patients were also enrolled who were undergoing colonoscopy for colorectal cancer screening or investigation of anemia. Histopathological abnormalities identified during colonoscopy were compared between the IBS and control groups.</p> <p>Results</p> <p>The average age of the IBS group was 46.13 ± 14.16 years and and the average age of the control group was 57.01 ± 13.07 years. The prevalence of microscopic colitis (MC) in the diarrhea predominant and the mixed subgroup of IBS patients was 4.32% (7/162) whereas in all IBS patients, the prevalence was 3.09% (7/226). MC was not found in the 152 control cases, (p = 0.045). Lymphocytic colitis was seen in 7 IBS patients, with 1 case in the mixed group and 6 cases in the diarrhea group and there was a significant difference in the frequency of lymphocytic colitis between the IBS subgroups (p < 0.01). Focal active colitis was found in 6.6% (15/226) of the IBS patients and in none of the controls (p < 0.01), and there was no differences between IBS subtypes.</p> <p>Conclusion</p> <p>Microscopic colitis was more often found in the diarrhea predominant/mixed subgroups of IBS patients and in patients who were older women. In patients who are older woman with non-constipated IBS, it may be reasonable to perform a biopsy to screen for microscopic colitis. Focal active colitis was significantly increased in patients with IBS compared to controls.</p

Artificial intelligence for detection of microsatellite instability in colorectal cancer-a multicentric analysis of a pre-screening tool for clinical application.

BACKGROUND Microsatellite instability (MSI)/mismatch repair deficiency (dMMR) is a key genetic feature which should be tested in every patient with colorectal cancer (CRC) according to medical guidelines. Artificial intelligence (AI) methods can detect MSI/dMMR directly in routine pathology slides, but the test performance has not been systematically investigated with predefined test thresholds. METHOD We trained and validated AI-based MSI/dMMR detectors and evaluated predefined performance metrics using nine patient cohorts of 8343 patients across different countries and ethnicities. RESULTS Classifiers achieved clinical-grade performance, yielding an area under the receiver operating curve (AUROC) of up to 0.96 without using any manual annotations. Subsequently, we show that the AI system can be applied as a rule-out test: by using cohort-specific thresholds, on average 52.73% of tumors in each surgical cohort [total number of MSI/dMMR = 1020, microsatellite stable (MSS)/ proficient mismatch repair (pMMR) = 7323 patients] could be identified as MSS/pMMR with a fixed sensitivity at 95%. In an additional cohort of N = 1530 (MSI/dMMR = 211, MSS/pMMR = 1319) endoscopy biopsy samples, the system achieved an AUROC of 0.89, and the cohort-specific threshold ruled out 44.12% of tumors with a fixed sensitivity at 95%. As a more robust alternative to cohort-specific thresholds, we showed that with a fixed threshold of 0.25 for all the cohorts, we can rule-out 25.51% in surgical specimens and 6.10% in biopsies. INTERPRETATION When applied in a clinical setting, this means that the AI system can rule out MSI/dMMR in a quarter (with global thresholds) or half of all CRC patients (with local fine-tuning), thereby reducing cost and turnaround time for molecular profiling

Microsatellite instability in colorectal cancer is associated with local lymphocyte infiltration and low frequency of distant metastases

Colorectal carcinomas (CRCs) with high microsatellite instability (MSI-H) share clinicopathological features distinctly different from their microsatellite stable (MSS) counterparts. Unlike MSS cancers, MSI-H CRCs occur predominantly in the right-sided colon and are often characterised by a strong lymphocyte infiltration. A poor differentiation pattern is found in most MSI-H CRCs, even though patients with MSI-H carcinomas seem to have a significantly longer survival after surgical resection. To clarify which factors contribute to the obvious paradoxon of a more favourable prognosis of MSI tumours, several clinical and histopathological features as well as the microsatellite status were evaluated in 120 colorectal cancer cases fulfilling clinical criteria (Bethesda) indicative for familial colorectal cancer. Microsatellite instablity status and lymphocyte infiltration were related to tumour stage and patients' follow-up. Statistical analysis confirmed well-known relations, such as enhanced lymphocyte infiltration accompanied by Crohn's like reaction (CLR) in MSI-H cancers (CLR+ in 27 out of 47 MSI-H vs 14 out of 71 MSS CRCs, P<0.001). However, after stratification for depth of local invasion and penetration of the primary tumour, T3 tumours displaying MSI had a significantly lower rate of distant metastases (M1 in four out of 35 MSI-H vs 20 out of 41 MSS CRCs, P<0.001). A similar tendency was observed for CLR-positive CRCs (M1 in six out of 29 CLR+ vs 17 out of 45 CLR− CRCs, P=0.13). In a logistic regression model, the MSI-H phenotype and the presence of CLR were independent predictors of a low UICC stage (P=0.006 and 0.04, respectively). These data, together with the recent definition of highly immunogenic neo-antigens expressed in MSI-H tumour cells, suggest that MSI-H CRCs elicit a protective host response that may prevent metastasis formation