Thrombolysis as a treatment for transplant renal artery thrombosis - a report of three unsuccessful cases and an overview of reported cases.

INTRODUCTION: Thrombolysis has been suggested as a feasible method to treat arterial renal transplant thrombosis under conditions of short duration of ischemia. Data on maximal duration of ischemia that are still feasible to treat are scarce. METHODS: We retrospectively analysed our experience involving three attempts to utilize thrombolysis to treat transplant renal artery thrombosis. We searched through literature on PubMed and compared the data we found with our own experience. RESULTS: In case number 1 of our cohort, thrombolysis was initiated 12 hours after the onset of thrombosis and had to be ceased after five hours due to the formation of a haematoma. Perfusion of the graft was restored but it did not regain function, most likely due to long ischemia time. In case number 2, an attempt to use thrombolysis was unsuccessful due to failure to cross the graft artery occlusion with a guidewire. Thrombosis was most likely caused by chronic rejection of the graft. In case number 3, thrombolysis restored arterial patency but, due to an onset of ischemia, which lasted 2 to 3 days, did not lead to restoration of graft function. The prolonged ischemia period in case three occurred, at least in part, due to failure to perform an ultrasound scan when the patient was first admitted. CONCLUSION: We can confirm that thrombolysis for transplant renal artery thrombosis seems to be feasible only when the condition has a short duration. In the event of sudden deterioration of graft function, the absence of perfusion must always be ruled out by ultrasound scan.

Confocal laser endomicroscopy in diagnosing indeterminate biliary strictures and pancreatic lesions a prospective pilot study.

INTRODUCTION: An accurate histopathological diagnosis of indeterminate biliary strictures and pancreatic lesions is challenging because of insufficient quali-ty of tissue specimen taken during ERCP (brush cytology), cholangioscopy (biopsies) or endosonography (EUS, FNAB). Confocal laser endomicroscopy (CLE) allows virtual histopathological diagnosis with the potential to either replace or increase the diagnostic yield of standard histopathological diagnosis in patients presenting with biliary strictures and pancreatic lesions. The aims of our prospective pilot study were to: 1. Assess the diagnostic yield of standard histopathology compared to CLE in patients referred for cholangioscopy or for EUS of the pancreas; 2. Evaluate the cost of CLE in these indications. METHODS: CLE was performed (during cholangioscopy or EUS), followed by standard tissue sampling. CLE-based diagnosis was compared with standard histopathology/cytology. CLE probe was introduced through the working channel of the cholangioscope or through the FNAB needle. RESULTS: A total of 23 patients were enrolled (12 women, mean age 61 years); 13 patients underwent cholangioscopy and 10 patients underwent EUS. Cholangioscopy: CLE diagnosed correctly all 4 malignant strictures (histology 2 of them only as 2 patients had insufficient quality of the tissue specimen). Agreement between standard histopathology and CLE was achieved in 85 %. EUS: All 3 cases of pancreatic cancer were correctly diagnosed by both CLE and FNAB. All remaining (premalignant and benign) lesions were also correctly diagnosed by both methods. The cost of CLE examination is higher compared to FNAB but comparable with tissue sampling during digital cholangioscopy. CONCLUSION: CLE demonstrated sufficient diagnostic accuracy in patients with indeterminate biliary strictures or pancreatic lesions and, therefore, might improve diagnostic accuracy or even replace standard histopathology in these indications.

Crohns disease of the appendix - a case report.

INTRODUCTION: Crohns disease is a chronic inflammatory autoimmune disease with unknown etiology. Although the disease may involve any part of the gastrointestinal tract, the most frequently affected site is the terminal ileum. Crohns disease itself is more common in women and in younger patients. Typical symptoms of the condition are diarrhoea, abdominal pain, weight loss and fever. A part of patients may present with extraintestinal symptoms like exanthema, joint pain, conjunctivitis or less often a hepatic lesion. In our publication, we have reported a rare case of Crohns disease with isolated involvement of the appendix, in which the definitive diagnosis was established after the surgery. CASE REPORT: Our patient presented with atypical symptoms and endoscopy findings. The majority of patients with Crohns disease of the appendix present as if they had acute appendicitis. CONCLUSION: Appendiceal form of Crohns disease is a relatively rare variety of Crohns disease and is less aggressive than in the other locations. Surgical resection (appendectomy) is considered to be curative and the risk of relapse is very low. Key words: Crohns disease - appendix differential diagnosis - treatment surveillance.

Confocal laser endomicroscopy in the diagnostics of gastrointestinal lesions literary review and personal experience.

INTRODUCTION: Confocal laser endomicroscopy (CLE) is a new method enabling real-time histopathological diagnosis. Two platforms of CLE are used standardly: the so called probe-based CLE in which an endomicroscopic probe is inserted through an endoscope, and so-called needle-based CLE inserted through a needle. METHODS: CLE enables evaluation of epithelial and subepithelial structures with 1000x magnification in any part of the gastrointestinal system. The main advantage over conventional biopsies can be immediate diagnosis and larger area evaluated. CLE might play a promising role in indeterminate biliary lesions where biopsies are often not sufficient and fail to allow for accurate diagnosis. CLE can also have a promising potential in pancreatic lesions where it is used along with the needle designed for tissue aspiration during endosonography. It is also possible to use CLE in other organ systems and medical specialties, e.g. in pneumology, neurosurgery, ENT and others. CONCLUSION: CLE is a promising diagnostic method; however, it is unlikely to replace standard biopsies currently since these are still considered a gold standard of histopathological diagnosis. High purchase price is a main disadvantage of the method, hampering its expansion in medicine. Key words: confocal laser endomicroscopy CLE biliary strictures pancreatic lesions esophageal carcinoma Rozhl Chir 2018;97:531-538.

Corrigendum for: Early Uterine Transplant Graft Loss Due to Thrombosis: Single-Center Experience With Causes, Prevention, Diagnosis, and Treatment.

On the basis of author's request the publisher of Physiological Research decided to change the license of the article to CC BY license.

Early Uterine Transplant Graft Loss Due to Thrombosis: Single-Center Experience With Causes, Prevention, Diagnosis, and Treatment.

Uterus transplantation (UTx) is a promising treatment option for women who wish to give birth but suffer from absolute uterine factor infertility. This paper presents an interim analysis of a trial focusing on the causes, prevention, diagnosis, and management of graft thrombosis. Our team analyzed 10 cases of UTx (recipients numbered 1 to 10). Early thrombosis developed in 2 of 10 (20 %) recipients, and thrombectomy and temporary viability preservation were achieved in both cases. However, re-thrombosis developed in both cases, and a graft hysterectomy was carried out. In recipient number 2, vascular changes might have contributed to graft thrombosis. The histopathological finding of the explant revealed subintimal excentric fibrosis with focal sclerotic changes. In recipient number 8, thrombosis was facilitated by external compression of the vascular pedicles by the hematoma as well as production of de novo donor-specific antibodies. Thrombosis led to graft loss in both cases despite an attempt at a thrombectomy. Therefore, the focus must be on prevention including a thorough evaluation of the donor candidate. In the postoperative course, perfusion is closely followed-up with an ultrasound, Doppler flow monitoring, and macroscopic evaluation of the cervix. In the event that findings are unclear, a relaparotomy should be promptly indicated. If thrombosis is revealed, a thrombectomy and an attempt to salvage the graft are indicated; however, the role of this strategy is questionable due to the low chance of long-term success. The indication of upfront graft removal and early re-transplantation in the treatment of uterine graft remains debatable.

Similar Microvascular Inflammation and Tubulointerstitial Injury in ABO-Incompatible and Matched ABO-Compatible Kidney Allografts.

ABO-incompatible (ABOi) kidney transplantation represents a viable tool to increase the donor pool for kidney transplantation, however, increased alloimmune response has been debated. The early outcomes of 25 low-risk ABOi kidney transplant recipients were compared with thoroughly matched 50 ABO-compatible (ABOc) ones. The matching process was based on gender and age of recipients and immunologic parameters, such as panel reactive antibodies, number of human leukocyte antigen mismatches, and transplantation era. Three-month protocol kidney graft biopsy Banff scores and 1-year clinical outcomes were compared. Apart from C4d positivity, no statistically significant differences were found regarding the Banff scores between the two groups. Similarly, microvascular inflammation and tubulointerstitial injury revealed no differences either. The eGFR at 3 months and 1 year was similar in both groups. In conclusion, blood group incompatibility yields no additional microvascular and tubulointerstitial graft injury if desensitization protocol was applied to low-risk kidney transplant recipients.

Sensitivity to perioperative ischemia/reperfusion injury in male and female donor myocardium.

Many functions of the cardiovascular apparatus are affected by gender. The aim of our study was find out whether markers of cell death present in the donor myocardium differ in male and female hearts. The study involved 81 patients undergoing heart transplantation from September 2010 to January 2013. Patients were divided into two groups: male allograft (n=49), and female allograft (n=32). Two types of myocardial cell death were analyzed. High-sensitive cardiac troponin T as a necrosis marker and protein bcl-2, caspase 3 and TUNEL as apoptosis markers were measured. We observed a significantly higher level of high-sensitive cardiac troponin T after correcting for predicted ventricular mass in female donors before transplantation as well as in the female allograft group after transplantation throughout the monitored period (P=0.011). There were no differences in apoptosis markers (bcl-2, caspase 3, TUNEL) between male and female hearts before transplantation. Both genders showed a significant increase of TUNEL-positive myocytes one week after transplantation without differences between the groups. Moreover, there were no differences in caspase 3 and bcl-2 expression between the two groups. Our results demonstrated the presence of necrotic and apoptotic cell death in human heart allografts. High-sensitive cardiac troponin T adjusted for predicted ventricular mass as a marker of myocardial necrosis was higher in female donors, and this gender difference was even more pronounced after transplantation.

Biomarkers of cellular apoptosis and necrosis in donor myocardium are not predictive of primary graft dysfunction.

Primary graft dysfunction (PGD) is a life-threatening complication among heart transplant recipients and a major cause of early mortality. Although the pathogenesis of PGD is still unclear, ischemia/reperfusion injury has been identified as a predominant factor. Both necrosis and apoptosis contribute to the loss of cardiomyocytes during ischemia/reperfusion injury, and this loss of cells can ultimately lead to PGD. The aim of our prospective study was to find out whether cell death, necrosis and apoptosis markers present in the donor myocardium can predict PGD. The prospective study involved 64 consecutive patients who underwent orthotopic heart transplantation at our institute between September 2010 and January 2013. High-sensitive cardiac troponin T (hs-cTnT) as a marker of minor myocardial necrosis was detected from arterial blood samples before the donor's pericardium was opened. Apoptosis (caspase-3, active + pro-caspase-3, bcl-2, TUNEL) was assessed from bioptic samples taken from the right ventricle prior graft harvesting. In our study, 14 % of transplant recipients developed PGD classified according to the standardized definition proposed by the ISHLT Working Group. We did not find differences between the groups in regard to hs-cTnT serum levels. The mean hs-cTnT value for the PGD group was 57.4+/-22.9 ng/l, compared to 68.4+/-10.8 ng/l in the group without PGD. The presence and severity of apoptosis in grafted hearts did not differ between grafts without PGD and hearts that subsequently developed PGD. In conclusion, our findings did not demonstrate any association between measured myocardial cell death, necrosis or apoptosis markers in donor myocardium and PGD in allograft recipients. More detailed investigations of cell death signaling pathways in transplanted hearts are required.

Is the amount of coronary perivascular fat related to atherosclerosis?

Interesting and stimulating data about the effect of the perivascular adipose tissue size on atherogenesis are based mainly on CT findings. We studied this topic by directly analyzing perivascular adipose tissue in explanted hearts from patients undergoing transplantation. Ninety-six consecutive patients were included, including 58 with atherosclerotic coronary heart disease (CHD) and 38 with dilation cardiomyopathy (DCMP). The area of perivascular fat, area of the coronary artery wall, and ratio of CD68-positive macrophages within the perivascular fat and within the vascular wall were quantified by immunohistochemistry. There was no significant difference in the perivascular adipose tissue size between the two groups. Nevertheless, there was a significantly higher number of macrophages in the coronary arterial wall of CHD patients. In addition, we found a close relationship between the ratio of macrophages in the arterial wall and adjacent perivascular adipose tissue in the CHD group, but not in the DCMP group. According to our data interaction between macrophages in the arterial wall and macrophages in surrounding adipose tissue could be more important mechanism of atherogenesis than the size of this tissue itself.

Comparison of the relative telomere length measured in leukocytes and eleven different human tissues.

The relative length of telomeres measured in peripheral blood leukocytes is a commonly used system marker for biological aging and can also be used as a biomarker of cardiovascular aging. However, to what extent the telomere length in peripheral leukocytes reflects telomere length in different organ tissues is still unclear. Therefore, we have measured relative telomere length (rTL) in twelve different human tissues (peripheral blood leukocytes, liver, kidney, heart, spleen, brain, skin, triceps, tongue mucosa, intercostal skeletal muscle, subcutaneous fat, and abdominal fat) from twelve cadavers (age range of 29 week of gestation to 88 years old). The highest rTL variability was observed in peripheral leukocytes, and the lowest variability was found in brain. We found a significant linear correlation between leukocyte rTL and both intercostal muscle (R=0.68, P<0.02) and liver rTL (R=0.60, P<0.05) only. High rTL variability was observed between different organs from one individual. Furthermore, we have shown that even slight DNA degradation (modeled by sonication of genomic DNA) leads to false rTL shortening. We conclude that the rTL in peripheral leukocytes is not strongly correlated with the rTL in different organs.

Co-cultivation of human aortic smooth muscle cells with epicardial adipocytes affects their proliferation rate.

The abnormal proliferation of vascular smooth muscle cells (VSMC) is thought to play a role in the pathogenesis of atherosclerosis. Adipocytes produce several bioactive paracrine substances that can affect the growth and migration of VSMCs. Our study focuses on the direct effect of the bioactive substances in conditioned media (CM) that was obtained by incubation with primary adipocyte-derived cell lines, including cell lines derived from both preadipocytes and from more mature cells, on the proliferation rate of human aortic smooth muscle cells (HAoSMCs). We used a Luminex assay to measure the adipokine content of the CM and showed that there was a higher concentration of monocyte chemoattractant protein-1 in renal preadipocyte-CM compared with the HAoSMC control (p<0.5). The addition of both renal preadipocyte- and epicardial adipocyte- CM resulted in the elevated production of vascular endothelial growth factor compared with the control HASoSMC CM (p<0.001). The adiponectin content in renal adipocyte-CM was increased compared to all the remaining adipocyte-CM (p<0.01). Moreover, the results showed a higher proliferation rate of HAoSMCs after co-culture with epicardial adipocyte-CM compared to the HAoSMC control (p<0.05). These results suggest that bioactive substances produced by adipocytes have a stimulatory effect on the proliferation of VSMCs.

A periadventitial sirolimus-releasing mesh decreased intimal hyperplasia in a rabbit model.

Autologous vein grafts used as aortocoronary bypasses are often prone to intimal hyperplasia, which results in stenosis and occlusion of the vein. The aim of this study was to prevent intimal hyperplasia using a newly developed perivascular system with sustained release of sirolimus. This system of controlled drug release consists of a polyester mesh coated with a copolymer of L-lactic acid and epsilon-caprolactone that releases sirolimus. The mesh is intended for wrapping around the vein graft during surgery. The mesh releasing sirolimus was implanted in periadventitial position onto arteria carotis communis of rabbits, and neointimal hyperplasia was then assessed. We found that implanted sirolimus-releasing meshes reduced intima thickness by 47+/-10 % compared to a vein graft after 3 weeks. The pure polyester mesh decreased vein intima thickness by 35+/-9 %. Thus, our periadventitial system for controlled release of sirolimus prevented the development of intimal hyperplasia in autologous vein grafts in vivo in rabbits. A perivascularly applied mesh releasing sirolimus is a promising device for preventing stenosis of autologous vein grafts.