Histomorphological Diagnosis of Ulcerative Colitis and Associated Conditions

Ulcerative colitis (UC) is a chronic, idiopathic inflammatory disease that affects mainly young adults. The histologic examination of endoscopic biopsies or resection specimens plays an important part in the diagnosis and follow up of patients with inflammatory bowel disease, including UC. In this chapter, we discuss on main histological features that can be used when analyzing endoscopic biopsies, as well as features that can be evaluated in surgical samples of patients with UC. The differential diagnosis toward Crohn’s disease and other mimickers is emphasized. In addition, the main complications associated with treatment and long-standing diseases, such as infection colitis and dysplasia are presented

Long-term survival of a patient with liver metastases from clear cell gastric adenocarcinoma after multimodality treatment including interventional oncology techniques

Background: Gastric cancer (GC) is the fourth most common cancer and the third leading cancer-related cause of death worldwide since most patients are diagnosed at an advanced stage. The majority of GCs are adenocarcinomas (ACs), and the poorly characterized clear cell AC represents a unique subgroup of GCs and is an independent marker of poor prognosis. Even though the prognosis for patients with advanced GC is poor we present a report of a patient with long-term survival despite having liver metastases from clear cell gastric AC. Case presentation: A 45-year-old male with clear cell gastric AC underwent subtotal gastrectomy and postoperative chemoradiation. Only a year and a half after his initial treatment the disease spread to his liver. He received two lines of chemotherapy treatment within the next two years before a right hepatectomy was suggested. Due to an initially insufficient future liver remnant (FLR), transarterial chemoembolization (TACE) and portal vein embolization (PVE) were performed, which made the surgical procedure possible. Shortly after a disease progression in the remaining liver was detected. In the following three years the patient was treated with a carefully planned combination of systemic therapy and different interventional oncology techniques including selective internal radiation therapy (SIRT) and TACE. And as illustrated, an attentive, patient-tailored, multimodality treatment approach can sometimes greatly benefit our patients as he had an overall survival of 88 months despite the poor prognosis of his disease. Conclusion: To the best of our knowledge, this report is the first to describe a patient with liver metastases from clear cell gastric AC treated with interventional oncology techniques (PVE, TACE, and SIRT) in combination with other locoregional and systemic therapies thereby presenting that these interventional oncology techniques can be successfully integrated into long-term management of non-conventional liver tumors

Histomorphological Assessment of Phlebitis in Renal Allografts

Cilj. Odrediti histomorfološka svojstva vena u normalnim i resađenim bubrezima. Postupci. Između 1992. i 1997. na Institutu za Patologiju u Ljubljani semikvantitativno smo određivali histomorfološke promjene u venama u 29 alogeničkih presadaka bubrega nakon odbacivanja i 31 kontrolnog bubrega. Dodatno smo analizirali i građu različitih odjeljaka bubrežnih vena. Rezultati. Male interlobularne vene satojale su se endotela i bazalne membrane, slično kapilarama, dok su stijenke velikih interloburalnih i arkuatnih vena imale snopove glatkih mišićnih stanica koji, su tvorili središnji sloj, slično velikim izvanbubrežnim venama. U kontrolnoj skupini, nađena je samo mononuklearna infiltracija oko malih interlobularnih vena (8/31). U odbačenim alogeničkim presadcima, bilo je mnoštvo vena infiltriranih upalnim stanicama, uglavnom limfocitima T i akrofagima (29/29). Ostale promjene su uključivale trombozu (16/29), fibroidnu nekrozu (7/29), i sklerozu (9/29), dok je u jednom slučaju zabilježeno taloženje lipida u intimi. Zaključak. Ovo istraživanje, provedeno na izvađenim uzorcima bubrega, otkrilo je da je vaskulitis koji nastaje zbog reakcije odbacivanja alogeničkoga presadka zahvatio izvanbubrežne i unutarbubrežne vene, koje su pokazale niz promjena sličnih onima u arterijama. S obzirom da velike trarenalne vene imaju mišićnu stijenku, vjerujemo da se izraz flebitis može opravdano rabiti u patologiji bubrežnih presadaka.Aim To evaluate the histomorphological features of veins in normal and transplanted kidneys. Methods Between 1992 and 1997, we semiquantitatively evaluated histomorphological changes in veins in nephrectomy specimens of 29 renal allografts with rejection and in 31 control kidneys. The structure of different segments of renal veins was additionally analyzed. Results Small interlobular veins were composed of endothelium and basement membrane, similar to capillaries, while the walls of large interlobular and arcuate veins had smooth muscle cell bundles forming the medial layer, similar to large extrarenal veins. In the control group, only focal mononuclear infiltration around small interlobular veins was found (8/31). In rejected kidney allografts, the veins were frequently infiltrated with inflammatory cells, predominantly T lymphocytes and macrophages (29/29). Other changes included thrombosis (16/29), fibrinoid necrosis (7/29), and sclerosis (9/29), and in one case an intimal lipid deposition. Conclusion This study, performed on whole explanted kidney specimens, revealed that rejection vasculitis often involved extrarenal and intrarenal veins, showing a whole spectrum of histopathological changes similar to those in arteries. Since large intrarenal veins have a muscle wall, we believe that the term “rejection phlebitis” could be used in renal transplant pathology

Vitamin A and retinoids in bladder cancer chemoprevention and treatment

Bladder cancer (BC) is the tenth most common cancer worldwide with a high recurrence rate, morbidity and mortality. Therefore, chemoprevention and improved treatment of BC are of paramount importance. Epidemiological studies suggest that adequate vitamin A intake may be associated with reduced BC risk. In addition, retinoids, natural and synthetic derivatives of vitamin A, are intensively studied in cancer research due to their antioxidant properties and their ability to regulate cell growth, differentiation, and apoptosis. Findings from in vivo and in vitro models of BC show great potential for the use of retinoids in the chemoprevention and treatment of BC. However, translation to the clinical practice is limited. In this narrative review we discuss: (i) vitamin A and retinoid metabolism and retinoic acid signalling, (ii) the pathobiology of BC and the need for chemoprevention, (iii) the epidemiological evidence for the role of dietary vitamin A in BC, (iv) mechanistic insights obtained from in vivo and in vitro models, (v) clinical trials of retinoids and the limitations of retinoid use, (vi) novel systems of retinoid delivery, and (vii) components of retinoid signalling pathways as potential novel therapeutic targets

Lectins as Biomarkers of IC/BPS Disease: A Comparative Study of Glycosylation Patterns in Human Pathologic Urothelium and IC/BPS Experimental Models

Pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) remains poorly understood, as well as its effective diagnosis and therapy. Studying changes in tissue glycosylation patterns under pathological conditions is a promising way of discovering novel biomarkers and therapeutic targets. The glycobiology of IC/BPS is largely understudied, therefore we compared glycosylation patterns of normal human urothelium with the urothelium of IC/BPS patients using a selection of 10 plant-based lectins with different monosaccharide preferences. We also compared lectin binding to human urothelium with the two most cited experimental models of IC/BPS, specifically, TNFα-treated human urothelial cell line RT4 and cyclophosphamide-induced chronic cystitis in C57BL6/J mice. Furthermore, binding of four of the selected lectins (ConA, DSL, Jacalin and WGA) was evaluated qualitatively by means of fluorescence microscopy, and quantitatively by fluorescence intensity (F.I.) measurements. Our results reveal a significant reduction in F.I. of Jacalin, as well as a prominent change in the WGA labeling pattern in the urothelium of IC/BPS patients, suggesting their potential use as promising additional biomarkers for histopathological diagnosis of IC/BPS. We have also shown that urothelial glycosylation patterns between selected experimental models and patients with IC/BPS are similar enough to offer an adequate platform for preclinical study of IC/BPS glycobiology

miR-200b, ZEB2 and PTPN13 Are Downregulated in Colorectal Carcinoma with Serosal Invasion

Serosal invasion is an independent negative prognostic factor in certain cancers, including CRC. However, the mechanisms behind serosal invasion are poorly understood. We therefore assumed that epithelial-mesenchymal transition (EMT) might be involved. Our study included 34 patients with CRC, 3 stage pT2, 14 stage pT3 and 17 showing serosal invasion (stage pT4a according to TNM staging system). RNA isolated from formalin-fixed paraffin-embedded tissue samples was analysed for expression of the miR-200 family and their target genes CDKN1B, ONECUT2, PTPN13, RND3, SOX2, TGFB2 and ZEB2 using real-time PCR. We found upregulation of miR-200b and ONECUT2 in CRC pT3 and pT4a compared to normal mucosa, and downregulation of CDKN1B in CRC pT3. Moreover, we observed, downregulation of miR-200b, PTPN13 and ZEB2 in CRC with serosal invasion (pT4a) compared to pT3. Our results suggest the involvement of partial EMT in serosal invasion of CRC. In addition, PTPN13 seems to be one of the important regulators involved in serosal invasion, and ONECUT2 in tumour growth