Cyclosporine A, FK-506, 40-O-[2-hydroxyethyl]rapamycin and mycophenolate mofetil inhibit proliferation of human intrahepatic biliary epithelial cells in vitro

AIM: To investigate the effect of cyclosporine A (CsA),FK-506, and mycophenolate mofetil (MMF) and 40-0-[2-hydroxyethyl]rapamycin (RAD) on proliferation of human intrahepatic biliary epithelial cells (BECs)in vitro.METHODS: BECs were isolated from six human liver tissuespecimens with the immunomagnetic separation method and treated with different concentrations of CsA, FK-506, RAD, and MMF in vitro. Proliferation of the cells was measured by MTT assay at 24 and 48 h after treatment, respectively. One-way analysis of variance was used to analyze the results. Expression of CK 19in BECs was monitored by flow cytometry and Western blot.RESULTS: Six lines of BECs were established. They survived for 4-18 wk in vitro. Flow cytometry analysis showed that these cells always expressed CK19. CsA,FK-506, RAD, and MMF inhibited proliferation of BECs in a dose-dependent manner. The lowest concentration of CsA, FK-506, RAD, and MMF to inhibit proliferation of BECs (P＜0.05) was 500, 100, 0.25, and 100 μg/L,respectively. However, the expression of CK19 by BECs was not changed.CONCLUSION: CsA, FK-506, RAD, and MMF have an antiproliferative effect on human intrahepatic BECs in vitro, while RAD has the strongest growth-inhibitory effect. Their possible effects on liver regeneration and bile duct injury in transplant patients should be further investigated.     

Cardiovascular magnetic resonance in myocardial infarction with non-obstructive coronary arteries patients: A review

The diagnosis of myocardial infarction with non-obstructive coronary arteries(MINOCA) necessitates documentation of an acute myocardial infarction(AMI),non-obstructive coronary arteries, using invasive coronary angiography or coronary computed tomography angiography and no clinically overt cause for AMI. Historically patients with MINOCA represent a clinical dilemma with subsequent uncertain clinical management. Differential diagnosis is crucial to choose the best therapeutic option for ischemic and non-ischemic MINOCA patients. Cardiovascular magnetic resonance(CMR) is able to analyze cardiac structure and function simultaneously and provides tissue characterization.Moreover, CMR could identify the cause of MINOCA in nearly two-third of patients providing valuable information for clinical decision making. Finally, it allows stratification of patients with worse outcomes which resulted in therapeutic changes in almost half of the patients. In this review we discuss the features of CMR in MINOCA; from exam protocols to imaging findings.     

Use of artificial intelligence in improving adenoma detection rate during colonoscopy: Might both endoscopists and pathologists be further helped

Colonoscopy remains the standard strategy for screening for colorectal cancer around the world due to its efficacy in both detecting adenomatous or precancerous lesions and the capacity to remove them intra-procedurally. Computeraided detection and diagnosis(CAD), thanks to the brand new developed innovations of artificial intelligence, and especially deep-learning techniques, leads to a promising solution to human biases in performance by guarantying decision support during colonoscopy. The application of CAD on real-time colonoscopy helps increasing the adenoma detection rate, and therefore contributes to reduce the incidence of interval cancers improving the effectiveness of colonoscopy screening on critical outcome such as colorectal cancer related mortality. Furthermore, a significant reduction in costs is also expected. In addition, the assistance of the machine will lead to a reduction of the examination time and therefore an optimization of the endoscopic schedule. The aim of this opinion review is to analyze the clinical applications of CAD and artificial intelligence in colonoscopy, as it is reported in literature, addressing evidence, limitations, and future prospects.     

Secondary haematological neoplasm after treatment of adult acute lymphoblastic leukaemia: analysis of 1170 adult ALL patients enrolled in the GIMEMA trials

Between 1983 and 1994 the incidence of secondary haematological neoplasms (SHM) was evaluated in 1170 new cases of ALL enrolled in the GIMEMA trials. Of the 942 patients who achieved complete remission (CR); seven developed a SHM: four AMLs and three NHLs.
The median latency from onset of ALL and of secondary haematological neoplasm was 69 months for AML and 61 months for NHL. Three out of four patients with secondary AML were unresponsive to the new chemotherapy and died, whereas the fourth patient achieved a new CR. Among the three NHL cases, two patients are presently alive in CR, whereas the third patient was refractory to chemotherapy and died.
The relative risk of haematological malignancy among the GIMEMA trials population, as compared to that of the Italian Cancer Registries, was 15.25-fold higher, and the actuarial estimated cumulative proportion of ALL patients with a secondary haematological neoplasm at 5 and 10 years were 0.59% and 3.63% respectively.
The incidence of adult ALL who developed a SHM, although apparently lower than in the paediatric ALL series, was higher when compared to the normal population. The difference between paediatric and adult ALL is probably due to the lack of craniospinal radiotherapy and to the lower doses of epipodoxiphyllotoxins used in adult trials. The higher percentage of childhood ALL with a prolonged event-free survival could result in an increase of secondary neoplasms in these cases, which suggests that secondary haematological neoplasms in adult ALL patients are real, although rare, events.     

Report: workshop on mediastinal grey zone lymphoma

Abstract:  There are several indications that classical Hodgkin lymphoma (cHL) and at least a proportion of cases of Primary Mediastinal B cell Lymphoma (PMBL) are derived from B cells at similar stages of differentiation and share common pathogenic mechanisms. The first indication was the existence of mediastinal grey zone lymphomas as identified in the 4th International Symposium on HL, with clinical, histological and immunohistochemical features intermediate between cHL and PMBL. Second, both tumor types resemble a cell that is developmentally situated in-between the germinal center reaction and a plasma cell. Third, cHL and PMBL were found to have similar gene expression profiles, including the lack of immunoglobulin expression and low levels of B cell receptor signalling molecules, and the secretion of molecules like the chemokine TARC and the prominent expression of IL-13 receptors. Fourth, both entities were found to have common genomic aberrancies, notably in 2p15 and 9p24, the sites of the REL oncogene and the tyrosine kinase gene JAK2, respectively. Further comparison of both lymphoma types may provide further insight in the pathogenic mechanisms and allow the design of diagnostic algorithms to sort out the small number of so-called mediastinal grey zone lymphomas, that appear to be intermediate between PMBL and cHL.     

Complete mesocolic excision and central vascular ligation in colorectal cancer in the era of minimally invasive surgery

Since the 19^th century, appropriate lymphadenectomy has been considered a cornerstone of oncologic surgery and one of the most important prognostic factors. This approach can be applied to any surgery for gastrointestinal cancer. During surgery for colon and rectal cancer, an adequate portion of the mesentery is removed together with the segment of bowel affected by the disease. The adequate number of lymph nodes to be removed is standardized and reported by several guidelines. It is mandatory to determine the appropriate extent of lymphadenectomy and to balance its oncological benefits with the increased morbidity associated with its execution in cancer patients. Our review focuses on the concept of “complete mesenteric excision (CME) with central vascular ligation (CVL),” a radical lymphadenectomy for colorectal cancer that has gained increasing interest in recent years. The aim of this study was to evaluate the evolution of this approach over the years, its potential oncologic benefits and potential risks, and the improvements offered by laparoscopic techniques. Theoretical advantages of CME are improved local-relapse rates due to complete removal of the intact mesocolic fascia and improved distance recurrence rates due to ligation of vessels at their origin (CVL) which guarantees removal of a larger number of lymph nodes. The development and worldwide diffusion of laparoscopic techniques minimized postoperative trauma in oncologic surgery, providing the same oncologic results as open surgery. This has been widely applied to colorectal cancer surgery; however, CME entails a technical complexity that can limit its wide minimally-invasive application. This review analyzes results of these procedures in terms of oncological outcomes, technical feasibility and complexity, especially within the context of minimally invasive surgery.