Number of intraepithelial lymphocytes and presence of a subepithelial band in normal colonic mucosa differs according to stainings and evaluation method.

Chronic watery diarrhea is a frequent symptom. In approximately 10% of the patients, a diagnosis of microscopic colitis (MC) is established. The diagnosis relies on specific, but sometimes subtle, histopathological findings. As the histology of normal intestinal mucosa vary, discriminating subtle features of MC from normal tissue can be challenging and therefore auxiliary stainings are increasingly used. The aim of this study was to determine the variance in number of intraepithelial lymphocytes (IELs) and presence of a subepithelial band in normal ileum and colonic mucosa, according to different stains and digital assessment. Sixty-one patients without diarrhea referred to screening colonoscopy due to a positive feacal blood test and presenting with endoscopically normal mucosa were included. Basic histological features, number of IELs, and thickness of a subepithelial band was manually evaluated and a deep learning-based algorithm was developed to digitally determine the number of IELs in each of the two compartments; surface epithelium and cryptal epithelium, and the density of lymphocytes in the lamina propria compartment. The number of IELs was significantly higher on CD3-stained slides compared with slides stained with Hematoxylin-and-Eosin (HE) (p<0.001), and even higher numbers were reached using digital analysis. No significant difference between right and left colon in IELs or density of CD3-positive lymphocytes in lamina propria was found. No subepithelial band was present in HE-stained slides while a thin band was visualized on special stains. Conclusively, in this cohort of prospectively collected ileum and colonic biopsies from asymptomatic patients, the range of IELs and detection of a subepithelial collagenous band varied depending on the stain and method used for assessment. As assessment of biopsies from patients with diarrhea constitute a considerable workload in the pathology departments digital image analysis is highly desired. Knowledge provided by the present study highlight important differences that should be considered before introducing this method in the clinic.

Vedolizumab as first-line biological therapy in elderly patients and those with contraindications for anti-TNF therapy: a real-world, nationwide cohort of patients with inflammatory bowel diseases.

BACKGROUND: Data from real-life populations about vedolizumab as first-line biological therapy for ulcerative colitis (UC) and Crohn's disease (CD) are emerging. OBJECTIVE: To investigate the efficacy and safety of vedolizumab in bio-naïve patients with UC and CD. METHODS: A Danish nationwide cohort study was conducted between November 2014 and November 2019. Primary outcomes were clinical remission, steroid-free clinical remission, and sustained clinical remission from weeks 14 through 52. RESULTS: The study included 56 patients (UC:31, CD:25) who initiated treatment with vedolizumab mainly because of contraindications to anti-TNFs, of whom 54.8 and 24.0%, respectively received systemic steroids at the initiation. Rates of clinical remission at weeks 6, 14, and 52 were 32.0, 48.0, and 40.0%, respectively, in UC, and 36.8, 36.8, and 47.4% in CD. Steroid-free clinical remission at week 52 was achieved among 36.0 and 47.4% of UC and CD patients, while sustained clinical remission was achieved in 32.0 and 36.8%. Lack of remission was associated with being female (68.8 vs. 11.1%, p = .01) in UC and non-structuring, non-penetrating behavior in CD (90.0 vs. 44.4%, p = .03); however, this was not confirmed in multivariate analysis. Discontinuation due to primary non-response occurred in 20.0 and 5.3% of UC and CD patients, respectively, while rates of secondary loss of response were 12.0 and 5.3% after 52 weeks of follow-up. Vedolizumab was well-tolerated as only one UC patient experienced a serious adverse event. CONCLUSION: Vedolizumab is effective in the achievement of short-term, long-term, and steroid-free clinical remission in bio-naïve UC and CD patients.

Course of Disease in Patients with Microscopic Colitis: A European Prospective Incident Cohort Study.

BACKGROUND AND AIMS: The disease course of microscopic colitis [MC] is considered chronic but benign. However, this assumption is based on mainly retrospective studies, reporting on incomplete follow-up of selective cohorts. Systematic, prospective and unbiased data to inform patients and healthcare professionals on the expected course of the disease and real-life response to therapy are warranted. METHODS: A prospective, pan-European, multi-centre, web-based registry was established. Incident cases of MC were included. Data on patient characteristics, symptoms, treatment and quality of life were systematically registered at baseline and during real-time follow-up. Four disease course phenotypes were discriminated and described. RESULTS: Among 381 cases with complete 1-year follow-up, 49% had a chronic active or relapsing disease course, 40% achieved sustained remission after treatment and 11% had a quiescent course. In general, symptoms and quality of life improved after 3 months of follow-up. A relapsing or chronic active disease course was associated with significantly more symptoms and impaired quality of life after 1 year. CONCLUSIONS: A minority of MC patients follow a quiescent disease course with spontaneous clinical improvement, whereas the majority suffer a chronic active or relapsing disease course during the first year after diagnosis, with persisting symptoms accompanied by a significantly impaired quality of life.

Modified percutaneous ethanol injection in the treatment of viscous cystic thyroid nodules.

Here we describe a prospective 2-year evaluation of the efficiency of a new procedure of percutaneous ethanol injection (PEI) treatment of viscous thyroid cystic nodules (VTCN). Three patients with VCTN were selected from a group of 22 patients with solitary thyroid cystic nodules. A modified two-stage ethanol injection procedure was planned for these patients. Stage 1 was performed through the injection of a small dose of ethanol into the nodule. The viscosity of the content was reduced within 2 weeks after the injection. In the second stage the nodule was decompressed and an established dose of sterile 95% ethanol was injected. Patients were followed up for 2 years. In all cases a reduction in nodule volume was found. In the following 18 months further reduction was observed, with an average of 91.7%. The effect was stable throughout the follow-up period. No complications were observed. Therefore, our new two-stage PEI procedure appears all efficient alternative approach for the treatment of VCTNs even if further investigations on a larger series are required.

Fluorescent diagnosis of urinary bladder cancer-a comparison of two diagnostic modalities.

UNLABELLED: White light cystoscopy (WLC) is considered to be a standard examination for localisation and surveillance of transitional cell cancer of urinary bladder. However, in patients who have undergone transurethral resection of bladder tumour (TUR-BT) sensitivity of this method is too low for early detection of cancer recurrence. In order to improve this unsatisfactory situation new diagnostic procedures are still under investigation. Fluorescent diagnosis is a modern diagnostic option based on the detection of distinctive fluorescence of normal and pathological tissue. Currently two techniques are in clinical use: autofluorescent diagnosis, also termed laser-induced fluorescence (LIF) and photodynamic diagnosis (PDD). In this study we have analysed sensitivity and specificity of the fluorescent diagnosis to validate the best mode of bladder cancer diagnosis. A total of 281 patients, after electroresection of bladder tumour due to transitional cell carcinoma, without any signs of tumour recurrence in white-light cystoscopy, were divided in two groups: 52 patients underwent PDD and in 229 patients autofluorescent diagnosis was performed. Bladder washings and excisions from suspicious red fluorescent spots were taken for histopathological and cytological analyses. Sensitivity and specificity of PDD equalled to 90.91 and 66.60%, respectively. In case of autofluorescence diagnosis these values amounted to: 97.83 and 70.07%, respectively. The overall sensitivity and specificity of fluorescent examination equalled to 96.49 and 69.46%, respectively. CONCLUSION: Autofluorescence diagnosis (LIF) of pathological lesions within urinary bladder has been proven to be more sensitive than PDD as evaluated by a non-parametrical test for structure indicators comparison (LIF versus PDD, P=0.0056).

Combined treatment of urinary bladder cancer with the use of photodynamic therapy (PDT) and subsequent BCG-therapy: a pilot study.

INTRODUCTION: Transitional cell carcinoma (TCC) of the urinary bladder is nowadays one of the most common cancers in young men. Similarly to other cancers TCC can be treated with curative intent when it is diagnosed very early. In recent years there has been an intensive development of treatment methods of urological diseases based on modern scientific discoveries, one of which is photodynamic therapy (PDT). This treatment in urology may be used either for pre-cancerous lesions, carcinoma in situ or for superficial tumours. PATIENTS AND METHODS: In this study, patients were subjected to PDT with subsequent BCG-therapy. In our study we demonstrate cases of 14 patients, who were under observation for minimum 24 months. All patients were diagnosed as having TCC in pathological stage pT1N0M0 (clinical: T1NxM0). They had previously undergone transurethral resection of bladder tumour (TUR-BT) and no exophytic tumours were observed. Patients were instillated intravesically with 4.5g of ALA (aminolevulinic acid) in buffered solution in the bladder for 2h. Afterwards, within 2h the bladder was irradiated with 635nm an argon-pumped dye laser light. Light power on the tip of the fibre was 1.0W. The total energy dose was 2000J equally divided into two to three sessions. RESULTS: After 24-month observation total response was observed in eight patients (in histopathological examination urocystitis was diagnosed), partial response (low- or high-grade dysplasia in microscopic examination) in two patients and no response in four patients (cancer cells in excised specimens). CONCLUSIONS: :

Autofluorescence endoscopy for detection of high-grade dysplasia in short-segment Barrett's esophagus.

BACKGROUND: The occurrence of precancerous lesions, such as high-grade dysplasia, in patients with short-segment Barrett's esophagus is controversial. This study assessed the efficacy of autofluorescence endoscopy for detection of high-grade dysplasia in short-segment Barrett's esophagus. METHODS: A total of 34 patients (28 men, 6 women; age range 40-77 years) with histopathologically proven short-segment Barrett's esophagus were studied. Autofluorescence endoscopy was performed by using monochromatized blue light (425-455 nm) filtered from a conventional xenon light source. A total of 136 and 109 biopsy specimens were taken from Barrett's mucosa under control, respectively, white light endoscopy and autofluorescence endoscopy. RESULTS: High-grade dysplasia was found in 9 (8.3%) autofluorescence-guided biopsy specimens, which was significantly greater than the number of white light endoscopy-guided biopsy specimens with this finding (one positive biopsy specimen, 0.7% of total biopsy specimens obtained). Autofluorescence endoscopy detected high-grade dysplasia in 7 patients, 6 more than were identified with white light endoscopy. In the one patient with high-grade dysplasia detected by white light endoscopy-guided biopsy specimens, autofluorescence-guided biopsy specimens revealed only low-grade dysplasia. CONCLUSION: Autofluorescence endoscopy in patients with short-segment Barrett's esophagus increases the detection rate of high-grade dysplasia.