Renal papillary carcinoma developed in a kidney transplant recipient with late IgA-nephropathy

With improvements in immunosuppressive therapy, patient and graft survival in renal transplant recipients have been prolonged. Increasing donor age and patient survival rates have been related to an increase in the number of de novo tumors. Posttransplant malignancy in these patients is an important cause of graft loss and death in these patients. Among cancers occurring after a kidney transplant, renal cell carcinoma is the fifth most common malignancy after lymphoproliferative disorders, and skin, gastrointestinal, and lung cancers. When nonmelanoma skin cancers and in situ carcinoma of the cervix are excluded from malignancies, renal cell carcinoma accounts for 2% of all cancers in the general population, which increases to 5% in solid-organ recipients. The majority of renal cell carcinomas found in transplant recipients develop in the recipient 's native kidneys, but only 9% of tumors develop in the allograft itself. Tumors transmitted by donors represent only 0.02% to 0.2% of cases. Most de novo allograft renal cell carcinomas are single tumors. The mechanisms of development of renal cell carcinoma in renal grafts are not completely understood

Metabolic syndrome and cardiovascular risk after liver transplantation: a single-center experience.

Excessive weight gain, hypertension, hyperlipidemia, and diabetes are frequently observed among orthotopic liver transplantation (OLT) patients. These alterations, which are probably multifactorial in origin, contribute to posttransplantation metabolic syndrome (PTMS), which increases the risk of cardiovascular events. We assessed the prevalence of PTMS (diagnosed according to modified NCEP Adult Treatment Panel III criteria) in 156 OLT patients undergoing regular follow-up after transplantation (median 68 months; range, 6 to 234 months). Several pre- and post-OLT data were collected to identify the factors associated with the presence of PTMS which was found in 28% of cases. The only independent predictive factors for PTMS were diabetes mellitus and patients who were overweight or obese before-OLT. The prevalence of PTSM was lower among patients on tacrolimus immunosuppression. In our population, 21% of patients showed a high cardiovascular risk score with a 4% incidence of cardiovascular events, which was higher among subjects with PTMS. Close follow-up is mandatory to prevent the development of PTMS mainly among overweight and diabetic patients before transplantation

Laparoscopy in liver transplantation: The future has arrived

In the last two decades, laparoscopy has revolutionized the field of surgery. Many procedures previously performed with an open access are now routinely carried out with the laparoscopic approach. Several advantages are associated with laparoscopic surgery compared to open procedures: reduced pain due to smaller incisions and hemorrhaging, shorter hospital length of stay, and a lower incidence of wound infections. Liver transplantation (LT) brought a radical change in life expectancy of patients with hepatic endstage disease. Today, LT represents the standard of care for more than fifty hepatic pathologies, with excellent results in terms of survival. Surely, with laparoscopy and LT being one of the most continuously evolving challenges in medicine, their recent combination has represented an astonishing scientific progress. The intent of the present paper is to underline the current role of diagnostic and therapeutic laparoscopy in patients waiting for LT, in the living donor LT and in LT recipients

Peribiliary glands as a niche of extra-pancreatic precursors yielding insulin-producing cells in experimental and human diabetes

Peribiliary glands (PBGs) are niches in the biliary tree and containing heterogeneous endodermal stem/progenitors cells that can differentiate, in vitro and in vivo, towards pancreatic islets. The aim of this study was to evaluate, in experimental and human diabetes, proliferation of cells in PBGs and differentiation of the biliary tree stem/progenitor cells (BTSCs) towards insulin-producing cells. Diabetes was generated in mice by intraperitoneal injection of a single dose of 200 mg/kg (N=12) or 120 mg/kg (N=12) of streptozotocin. Liver, pancreas and extrahepatic biliary trees were en bloc dissected and examined. Cells in PBGs proliferated in experimental diabetes, and their proliferation was greatest in the PBGs of the hepato-pancreatic ampulla, and inversely correlated with the pancreatic islet area. In rodents, the cell proliferation in PBGs was characterized by the expansion of Sox9-positive stem/progenitor cells that gave rise to insulin-producing cells. Insulin-producing cells were located mostly in PBGs in the portion of the biliary tree closest to the duodenum, and their appearance was associated with up-regulation of MafA and Gli1 gene expression. In patients with type 2 diabetes, PBGs at the level of the hepato-pancreatic ampulla contained cells showing signs of proliferation and pancreatic fate commitment. In vitro, high glucose concentrations induced the differentiation of human BTSCs cultures towards pancreatic beta cell fates. The cells in PBGs respond to diabetes with proliferation and differentiation towards insulin-producing cells indicating that PBG niches may rescue pancreatic islet impairment in diabetes. These findings offer important implications for the patho-physiology and complications of this disease. This article is protected by copyright. All rights reserved

Fluctuations of estimated glomerular filtration rate outside kidney disease improving global outcomes diagnostic criteria for acute kidney injury in end-stage liver disease outpatients and outcome postliver transplantation

Background. Renal dysfunction in end-stage liver disease (ESLD) results fromsystemic conditions that affect both liver and kidney with activation of vasoconstrictor systems. In this setting, estimated glomerular filtration rate (eGFR) may undergo variations often outside Kidney Disease Improving Global Outcomes criteria for acute kidney injury (AKI) diagnosis, whose meaning is not clear. The aim of this study was to evaluate eGFR variations in ESLD outpatients listed for liver transplant (liver Tx) and the association with post-Tx outcome. Methods. Fifty-one patients with ESLD were retrospectively evaluated from listing to transplant (L-Tx time), intraoperatively (Tx time), and up to 5 years post-Tx time. Variations between the highest and the lowest eGFR occurring in more than 48 hours, not satisfying Kidney Disease Improving Global Outcomes guideline, were considered as fluctuations (eGFR-F). Fluctuations of eGFR greater than 50%were defined as eGFR drops (DeGFR). Early graft dysfunction, AKI within 7 days, chronic kidney disease, and short- and long-term patient survivals were considered as outcomes. Results. All patients presented eGFR-F, whereas DeGFR were observed in 18 (35.3%) of 51 (DeGFR+ group). These patients presented higher levels of Model for End-stage Liver Disease score, pre-Tx bilirubin and significantly greater incidence of post-Tx AKI stages 2 to 3 compared with patients without drops (DeGFR−). DeGFR was the only independent predictive factor of the occurrence of post-Tx AKI. The occurrence of AKI post-Tx was associated with the development of chronic kidney disease at 3 months and 5 years post-Tx. Conclusions. Drops of eGFR are more frequently observed in patients with a worse degree of ESLD and are associated with a worse post-Tx kidney outcome

MULTIPLE ORGAN HARVESTING: EVOLUTION OF SURGICAL TECHNIQUE. PERSONAL EXPERIENCE

SINCE 1950, kidney, liver, heart, and lung transplantations have dramatically improved, emerging as the elective treatment modality for organ failure. Nevertheless, the indications to pancreas and bowel grafting are stili controversial. Several factors have contributed such results, namely the introduction of cyclosporine (CyA) in 1981, the use of new solutions for solid organ preservation (eg, the University of Wisconsin solution), the improvement in donor selection criteria, intensive care, as well as improvement management of transplant operation and harvesting surgical technique

Effects of probiotic bacteria (VSL#3) on the polyamine biosynthesis and cell proliferation of normal colonic mucosa of rats

Abstract. Background: Probiotics seem to possess tumour inhibitory properties, but few studies have investigated their actions on the cell proliferation of normal colonic mucosa. The effects of a probiotic mixture (VSL#3) on polyamine biosynthesis, Ki-67 levels and apoptosis in the normal colon of rats were studied. Materials and Methods: For a 4-week period, 20 rats were fed a VSL#3 solution and 20 rats a saline solution. Samples from the colonic mucosa were collected at the end of treatment. Polyamines were detected by HPLC, ornithine decarboxylase activity by a radiometric technique, and apoptosis and Ki-67 by histochemical and immunohistochemical methods. Results: VSL#3 caused a significant decrease in colonic polyamine levels, ornithine decarboxylase activity and Ki-67 compared to controls. A significant increase in the apoptotic index was also observed. Conclusion: Probiotics could also reduce proliferation rates in a condition not affected by hyperproliferative or neoplastic growth, when the normal control mechanisms are still completely effective

Simulated microgravity promotes the formation of tridimensional cultures and stimulates pluripotency and a glycolytic metabolism in human hepatic and biliary tree stem/progenitor cells

Many pivotal biological cell processes are affected by gravity. The aim of our study was to evaluate biological and functional effects, differentiation potential and exo-metabolome profile of simulated microgravity (SMG) on human hepatic cell line (HepG2) and human biliary tree stem/progenitor cells (hBTSCs). Both hBTSCs and HepG2 were cultured in a weightless and protected environment SGM produced by the Rotary Cell Culture System (Synthecon) and control condition in normal gravity (NG). Self-replication and differentiation toward mature cells were determined by culturing hBTSCs in Kubota's Medium (KM) and in hormonally defined medium (HDM) tailored for hepatocyte differentiation. The effects on the expression and cell exo-metabolome profiles of SMG versus NG cultures were analyzed. SMG promotes tridimensional (3D) cultures of hBTSCs and HepG2. Significative increase of stemness gene expression (p < 0.05) has been observed in hBTSCs cultured in SMG when compared to NG condition. At the same time, the expression of hepatocyte lineage markers in hBTSCs differentiated by HDM was significantly lower (p < 0.05) in SMG compared to NG, demonstrating an impaired capability of hBTSCs to differentiate in vitro toward mature hepatocytes when cultured in SMG condition. Furthermore, in HepG2 cells the SMG caused a lower (p < 0.05 vs controls) transcription of CYP3A4, a marker of late-stage (i.e. Zone 3) hepatocytes. Exo-metabolome NMR-analysis showed that both cell cultures consumed a higher amount of glucose and lower glutamate in SMG respect to NG (p < 0.05). Moreover, hBTSCs media cultures resulted richer of released fermentation (lactate, acetate) and ketogenesis products (B-hydroxybutyrate) in SGM (p < 0.05) than NG. While, HepG2 cells showed higher consumption of amino acids and release of ketoacids (3-Methyl-2-oxovalerate, 2-oxo-4-methyl-valerate) and formiate with respect to normogravity condition (p < 0.05). Based on our results, SMG could be helpful for developing hBTSCs-derived liver devices. In conclusion, SMG favored the formation of hBTSCs and HepG2 3D cultures and the maintenance of stemness contrasting cell differentiation; these effects being associated with stimulation of glycolytic metabolism. Interestingly, the impact of SMG on stem cell biology should be taken into consideration for workers involved in space medicine programs

Gallbladder stem/progenitor cells are able to repopulate and rescue the damaged liver in a experimental mouse model of liver cirrhosis

[No abstract available]The human biliary tree contains stem cells within peribiliary glands (Cardinale et al., 2011). Human Gallbladder contains stem/progenitors (hGSCs) located in mucosal crypts (Carpino et al., 2012). Our aim was to evaluate the capability of hGSCs to repopulate and rescue the damaged liver in a model of liver cirrhosis. hGSCs were selected for Epithelial Cell Adhesion Molecule. Cirrhosis was induced by intraperitoneal injection, twice a week, of carbon tetrachloride for 7 weeks. hGSCs were injected into the liver via the spleen of normal or cirrhotic SCID mice. As controls, cirrhotic SCID mice were injected only with the medium or with mature human hepatocytes. 2 months after the injection, the necrotic areas were lower in mice treated with hGSCs in comparison with controls. In hGSCs-injected cirrhotic mice, the expression of the human antigens indicated that ≈10% of the host hepatocyte mass was represented by in vivo differentiated human hepatocytes derived from injected hGSCs. This value was significantly higher with respect to mice injected with human adult hepatocytes. The presence of human cells in murine livers was confirmed by in situ hybridization for human chromosomes. hGSCs injection dictated an improvement of serum liver biochemistry with a significant reduction of transaminases and an improvement of synthetic functions. In this model, hGSC engraftment and differentiation determinate the improvement of histological liver damage and serum liver biochemistry. These data could open future perspectives for a role of gallbladder as a source of stem cells for liver regenerative medicine

Progenitor cell niches in the human pancreatic duct system and associated pancreatic duct glands: an anatomical and immunophenotyping study

Abstract Pancreatic duct glands (PDGs) are tubule‐alveolar glands associated with the pancreatic duct system and can be considered the anatomical counterpart of peribiliary glands (PBGs) found within the biliary tree. Recently, we demonstrated that endodermal precursor niches exist fetally and postnatally and are composed functionally of stem cells and progenitors within PBGs and of committed progenitors within PDGs. Here we have characterized more extensively the anatomy of human PDGs as novel niches containing cells with multiple phenotypes of committed progenitors. Human pancreata (n = 15) were obtained from cadaveric adult donors. Specimens were processed for histology, immunohistochemistry and immunofluorescence. PDGs were found in the walls of larger pancreatic ducts (diameters > 300 μm) and constituted nearly 4% of the duct wall area. All of the cells identified were negative for nuclear expression of Oct4, a pluripotency gene, and so are presumably committed progenitors and not stem cells. In the main pancreatic duct and in large interlobular ducts, Sox9+ cells represented 5–30% of the cells within PDGs and were located primarily at the bottom of PDGs, whereas rare and scattered Sox9+ cells were present within the surface epithelium. The expression of PCNA, a marker of cell proliferation, paralleled the distribution of Sox9 expression. Sox9+PDG cells proved to be Pdx1+/Ngn3+/–/Oct4A−. Nearly 10% of PDG cells were positive for insulin or glucagon. Intercalated ducts contained Sox9+/Pdx1+/Ngn3+ cells, a phenotype that is presumptive of committed endocrine progenitors. Some intercalated ducts appeared in continuity with clusters of insulin‐positive cells organized in small pancreatic islet‐like structures. In summary, PDGs represent niches of a population of Sox9+ cells exhibiting a pattern of phenotypic traits implicating a radial axis of maturation from the bottoms of the PDGs to the surface of pancreatic ducts. Our results complete the anatomical background that links biliary and pancreatic tracts and could have important implications for the common patho‐physiology of biliary tract and pancreas