Morbidity associated with intraportal islet transplantation
Pascal BucherZ. MáthéDomenico BoscoChristoph R. BeckerL. KesslerM. GregetPierre‐Yves BenhamouAxel AndrèsJosé OberholzerLéo H. BühlerP. MorelThierry Berney
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Many factors influence the outcome of islet transplantation. As islets in the early posttransplant setting are supplied with oxygen by diffusion only and are in a hypoxic state in the portal system, we tested whether small human islets are superior to large islets both in vitro and in vivo. We assessed insulin secretion of large and small islets and quantified cell death during hypoxic conditions simulating the intraportal transplant environment. In the clinical setting, we analyzed the influence of transplanted islet size on insulin production in patients with type 1 diabetes. Our results provide evidence that small islets are superior to large islets with regard to in vitro insulin secretion and show a higher survival rate during both normoxic and hypoxic culture. Islet volume after 48 h of hypoxic culture decreased to 25% compared with normoxic culture at 24 h due to a preferential loss of large islets. In human islet transplantation, the isolation index (islet volume as expressed in islet equivalents/islet number), or more simply the islet number, proved to be more reliable to predict stimulated C-peptide response compared with islet volume. Thus, islet size seems to be a key factor determining human islet transplantation outcome.
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Surgical stress
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Introduction: The challenging process of obtaining pure islet fractions from donor pancreata hampers the widespread use of allogenic islet transplantation for patients with complicated diabetes mellitus. Limited evidence suggests that transplantation of islet products with a higher percentage of non-islet cells is associated with improved long-term metabolic outcomes. However, conclusive evidence is lacking due to indirect metabolic outcome measurements, the small number of islet recipients, and the lack of an objective and reproducible assessment of islet purity. We aimed to retrospectively evaluate the effect of islet purity on long-term graft function using robust measurement methods to determine islet purity and graft function. Method: In a cohort of islet recipients that underwent an allogenic islet transplantation procedure at Leiden University Medical Center, digitalized microscopic images of the dithizone-stained transplanted islet graft were analyzed using a reproducible computerized deep learning method (IsletNet, version 2020-01-20) to calculate islet purity (expressed as %), islet size index (estimate of the average islet size, index <1 indicates an average islet size <150 μm) and the percentage of embedded islets. The cohort was divided into tertiles based on the purity: low purity (0–38%), intermediate purity (39–58%) and high purity (59–100%). Short- and long-term graft function was evaluated by calculating the area-under-the-curve (AUC) of C-peptide measurements that were obtained with mixed meal tests three months after transplantation, and subsequently yearly up to 5 years. Results: Forty-one islet transplantation patients were included. Twenty-eight grafts consisted of islets derived from 1 donor pancreas and 13 grafts from 2 donor pancreata. The purity (mean±sd) in the low, intermediate and high group was 26±10, 46±6 and 67±7%, respectively. A higher islet purity was positively associated with islet size index (R2=0.47, p<0.0001) and negatively associated with the percentage of embedded islets (R2=0.56, p<0.0001). The C-peptide AUC (mean±sd) at three months after transplantation was 125.4±74.0 (low purity), 107.7±57.1 (intermediate purity), and 172.4±73.0 nmol/L (high purity; high vs low purity p=0.11). Also at 5 years there was no clear difference in C-peptide AUC (mean±sd): 55.5± 65.7 (low purity), 115.2±62.3 (intermediate purity) and 96.0±84.2 nmol/L (high purity). Conclusion: The use of higher purity islet grafts for transplant is not associated with better long-term graft function. Further investigations are required to elucidate the mechanisms underlying the effect of non-islet cells on long-term islet function.
Allotransplantation
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Clinical islet allotransplantation is dependent on the ability to achieve a high yield and purity of islets isolated from human cadaver pancreas donors. The aim of this study was to determine the factors influencing the pancreas prior to islet isolation that may alter yield and purity. The results of 50 consecutive islet isolations from cadaver donor human pancreati at the University of Chicago Medical Center from December 1991 to April 1993 were analyzed. All pancreati were first offered for whole pancreas transplantation before being considered for islet isolation. Human pancreatic islet isolation was accomplished by a modified automated method. Some islet isolations resulted in a high islet yield but low islet purity. Other resulted in well-purified islets, but a low yield. Arbitrarily, successful islet isolation is defined as that yielding over 250,000 islet equivalents (EQN) with a purity of at least 80%. The success rate of human pancreatic islet isolation was 70%. The mean final islet yield obtained from these 50 pancreati was 300,000±131,000 islet EQN. The mean purity of the final preparation was 73%±25%. By univariate analysis, five factors were found to affect significantly the yield, purity, or overall success rate of islet isolation: organ cold ischemic time, donor age, donor plasma glucose levels, donor body weight, and cause of donor death. Even when islet isolation was successful, the function of islets from hyperglycemic and older donors appear to be impaired both in vitro and in vivo. These results suggest that islet yield and purity are affected by multiple donor-related factors. Even when adequate yield and purity are obtained, islet function is also dependent on donor variables.
Allotransplantation
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Mini laparotomy is technical for the resection of colorectal cancer (CRC) in selected patients. The aim was to compare clinical outcomes of mini laparotomy with conventional laparotomy in CRC patients.Between january 2007 and june 2010, 138 patients and 117 patients underwent elective resection using either mini laparotomy or conventional laparotomy respectively. Mini laparotomy involved a colorectal resection performed through a skin incision ≤8 cm in length. Clinicopathological factors, operative procedure and postoperative course were retrospectively analyzed to compare clinical outcomes between the two groups.Mini laparotomy seems to be an attractive alternative for resection of CRC in selected patients. Clinicopathological and histopathological features were similar between both groups, whereas intraoperative blood loss, operative time and harvested lymph-node numbers in conventional laparotomy were significantly greater (p=0.003, p=0.008 and p=0.024, respectively). Postoperative relapse, complications and hospitalization were significantly better in the mini laparotomy (all p<0.001). In comparison of postoperative complications between convention and mini laparotomy, ileus was more frequently encountered in conventional group (p=0.001). Interestingly, the disease-free survival and overall survival in mini laparotomy group were significantly better than control group (p=0.001 and p=0.017, respectively).Compared to conventional laparotomy, mini laparotomy seems a feasible, minimally invasive and attractive alternative in selected patients.
Ileus
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Biocompatibility
Pancreatic Islets
Cell Survival
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Purpose Negative laparotomy in patients with abdominal penetrating injuries (APIs) is associated with deleterious outcomes and unnecessary expense; however, the indications for laparotomy in hemodynamically stable patients with ambiguous computed tomography (CT) findings remain unclear. This study aimed to identify the factors associated with negative laparotomy. findings Methods Data of patients who underwent laparotomy for APIs between 2011 and 2019 were retrospectively reviewed. Patients who presented with definite indications for laparotomy were excluded. The patients were dichotomized into negative and positive laparotomy groups, and the baseline characteristics, laboratory test results, and CT findings were compared between the groups. Results Of 55 patients with ambiguous CT findings, 38 and 17 patients were assigned to the negative and positive laparotomy groups, respectively. There was no significant difference between the groups with respect to the baseline characteristics or the nature of the ambiguous CT findings. However, the laboratory test results showed that there was a difference in the percentage of neutrophils between the groups (negative: 55.6% [range 47.4â66.1%] vs. positive: 79.8% [range 77.6â88.2%], p<0.001), although the total white blood cell count was not significantly different. The mean duration of hospital stay for the negative laparotomy group was 13.1 days, and seven patients (18.4%) experienced complications. Conclusions Diagnostic factors definitively indicative of laparotomy were not identified, although the percentage of neutrophils might be helpful. However, routine laparotomy in patients with peritoneal injuries could result in instances of negative laparotomy. Keywords: Abdominal injuries; Wounds, penetrating; Laparotomy
Abdominal computed tomography
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