original articleT h e ne w e ngl a nd jou r na l o f m e dic i ne n engl j med 355;13 www.nejm

OBJECTIVEIt is generally admitted that the endocrine cell organization in human islets is different from that of rodent islets. However, a clear description of human islet architecture has not yet been reported. The aim of this work was to describe our observations on the arrangement of human islet cells.RESEARCH DESIGN AND METHODSHuman pancreas specimens and isolated islets were processed for histology. Sections were analyzed by fluorescence microscopy after immunostaining for islet hormones and endothelial cells.RESULTSIn small human islets (40–60 μm in diameter), β-cells had a core position, α-cells had a mantle position, and vessels laid at their periphery. In bigger islets, α-cells had a similar mantle position but were found also along vessels that penetrate and branch inside the islets. As a consequence of this organization, the ratio of β-cells to α-cells was constantly higher in the core than in the mantle part of the islets, and decreased with increasing islet diameter. This core-mantle segregation of islet cells was also observed in type 2 diabetic donors but not in cultured isolated islets. Three-dimensional analysis revealed that islet cells were in fact organized into trilaminar epithelial plates, folded with different degrees of complexity and bordered by vessels on both sides. In epithelial plates, most β-cells were located in a central position but frequently showed cytoplasmic extensions between outlying non–β-cells.CONCLUSIONSHuman islets have a unique architecture allowing all endocrine cells to be adjacent to blood vessels and favoring heterologous contacts between β- and α-cells, while permitting homologous contacts between β-cells.

There is a crucial need for noninvasive assessment tools after cell transplantation. This study investigates whether a magnetic resonance imaging (MRI) strategy could be clinically applied to islet transplantation. The purest fractions of seven human islet preparations were labeled with superparamagnetic iron oxide particles (SPIO, 280 lg/mL) and transplanted into four patients with type 1 diabetes. MRI studies (T2 * ) were performed prior to and at various time points after transplantation. Viability and in vitro and in vivo functions of labeled islets were similar to those of control islets. All patients could stop insulin after transplantation. The first patient had diffuse hypointense images on her baseline liver MRI, typical for spontaneous high iron content, and transplant-related modifications could not be observed. The other three patients had normal intensity on pretransplant images, and iron-loaded islets could be identified after transplantation as hypointense spots within the liver. In one of them, i.v. iron therapy prevented subsequent visualization of the spots because of diffuse hypointense liver background. Altogether, this study demonstrates the feasibility and safety of MRI-based islet graft monitoring in clinical practice. Iron overload (spontaneous or induced) represents the major obstacle to the technique.

A complementary DNA for a glucagon-like peptide-1 receptor was isolated from a human pancreatic islet cDNA library. The isolated clone encoded a protein with 90% identity to the rat receptor. In stably transfected fibroblasts, the receptor bound I n normal individuals, oral glucose absorption induces a greater insulin secretory response than an isoglycemic intravenous glucose infusion. This greater effect of oral glucose results from the secretion of intestinal hormones, which, at the level of the pancreatic p-cells, potentiate glucose-induced insulin secretion (1,2). These

Elective left-sided colorectal surgery without MBP is safe and is associated with reduced postoperative morbidity.

We exploited the ability of lentiviral vectors to govern the stable transduction of cells irrespective of their cycling status to induce the reversible immortalization of human primary cells. First, bicistronic HIV-derived lentiviral vectors expressing GFP- and the HSV1 thymidine kinase and containing the LoxP sequence in their LTR (HLox) were used to transduce HeLa cells. Cre expression led to efficient proviral deletion, and unexcised cells could be eliminated by ganciclovir treatment. A human liver biopsy was then exposed to a combination of HLox vectors that harbored either the SV40 large T (TAg) or the human telomerase (hTERT) DNAs in place of GFP. This led to the isolation of liver sinusoidal endothelial cell (LSEC) clones that exhibited an immortalized phenotype while retaining most of the features of primary hLSEC. Complete growth arrest of these cells was observed in 2 days of Cre expression, and the resulting stationary culture could be kept for at least 2 weeks. Transduction of human adult pancreatic islets with HLox vectors coding for Tag and Bmi-1 also induced the proliferation of insulin-positive cells. These results indicate that lentivectors can be used to mediate the reversible immortalization of primary nondividing cells and should allow for the production of large supplies of a wide variety of human cells for both therapeutic and research purposes.

The aim of the present study was to describe the current situation of donation after circulatory death (DCD) in the Council of Europe, through a dedicated survey. Of 27 participating countries, only 10 confirmed any DCD activity, the highest one being described in Belgium, the Netherlands and the United Kingdom (mainly controlled) and France and Spain (mainly uncontrolled). During 2000-2009, as DCD increased, donation after brain death (DBD) decreased about 20% in the three countries with a predominant controlled DCD activity, while DBD had increased in the majority of European countries. The number of organs recovered and transplanted per DCD increased along time, although it remained substantially lower compared with DBD. During 2000-2008, 5004 organs were transplanted from DCD (4261 kidneys, 505 livers, 157 lungs and 81 pancreas). Short-term outcomes of 2343 kidney recipients from controlled versus 649 from uncontrolled DCD were analyzed: primary non function occurred in 5% vs. 6.4% (P = NS) and delayed graft function in 50.2% vs. 75.7% (P < 0.001). In spite of this, 1 year graft survival was 85.9% vs. 88.9% (P = 0.04), respectively. DCD is increasingly accepted in Europe but still limited to a few countries. Controlled DCD might negatively impact DBD activity. The degree of utilization of DCD is lower compared with DBD. Short-term results of DCD are promising with differences between kidney recipients transplanted from controlled versus uncontrolled DCD, an observation to be further analyzed

BackgroundDecreasing anastomotic leak rates remain a major goal in colorectal surgery. Assessing intraoperative perfusion by indocyanine green (ICG) with near‐infrared (NIR) visualization may assist in selection of intestinal transection level and subsequent anastomotic vascular sufficiency. This study examined the use of NIR‐ICG imaging in colorectal surgery.MethodsThis was a prospective phase II study (NCT02459405) of non‐selected patients undergoing any elective colorectal operation with anastomosis over a 3‐year interval in three tertiary hospitals. A standard protocol was followed to assess NIR‐ICG perfusion before and after anastomosis construction in comparison with standard operator visual assessment alone.ResultsFive hundred and four patients (median age 64 years, 279 men) having surgery for neoplastic (330) and benign (174) pathology were studied. Some 425 operations (85·3 per cent) were started laparoscopically, with a conversion rate of 5·9 per cent. In all, 220 patients (43·7 per cent) underwent high anterior resection or reversal of Hartmann's operation, and 90 (17·9 per cent) low anterior resection. ICG angiography was achieved in every patient, with a median interval of 29 s to visualization of the signal after injection. NIR‐ICG assessment resulted in a change in the site of bowel division in 29 patients (5·8 per cent) with no subsequent leaks in these patients. Leak rates were 2·4 per cent overall (12 of 504), 2·6 per cent for colorectal anastomoses and 3 per cent for low anterior resection. When NIR‐ICG imaging was used, the anastomotic leak rates were lower than those in the participating centres from over 1000 similar operations performed with identical technique but without NIR‐ICG technology.ConclusionRoutine NIR‐ICG assessment in patients undergoing elective colorectal surgery is feasible. NIR‐ICG use may change intraoperative decisions, which may lead to a reduction in anastomotic leak rates.