This prospective phase 1/2 trial investigated the safety and reproducibility of allogeneic islet transplantation (Tx) in type I diabetic (T1DM) patients and tested a strategy to achieve insulin-independence with lower islet mass. Ten C-peptide negative T1DM subjects with hypoglycemic unawareness received 1-3 intraportal allogeneic islet Tx and were followed for 15 months. Four subjects (Group 1) received the Edmonton immunosuppression regimen (daclizumab, sirolimus, tacrolimus). Six subjects (Group 2) received the University of Illinois protocol (etanercept, exenatide and the Edmonton regimen). All subjects became insulinindependent. Group 1 received a mean total number of islets (EIN) of 1460 080 ± 418 330 in 2 (n = 2) or 3 (n = 2) Tx, whereas Group 2 became insulin-independent after 1 Tx (537 495 ± 190 968 EIN, p = 0.028). All Group 1 subjects remained insulin free through the follow-up. Two Group 2 subjects resumed insulin: one after immunosuppression reduction during an infectious complication, the other with exenatide intolerance. HbA1c reached normal range in both groups (6.5 ± 0.6 at baseline to 5.6 ± 0.5 after 2-3 Tx in Group 1 vs. 7.8 ± 1.1 to 5.8 ± 0.3 after 1 Tx in Group 2). HYPO scores markedly decreased in both groups. Combined treatment of etanercept and exenatide improves islet graft function and facilitates achievement of insulin-independence with less islets.
Robot-assisted pancreaticoduodenectomy can be performed safely in elderly patients with comparable mortality, morbidity, and outcomes compared with a younger population. Age alone should not be a contraindication for robotic pancreatic resection.
Microencapsulation may allow for immunosuppression-free islet transplantation. Herein we investigated whether human islets can be shipped safely to a remote encapsulation core facility and maintain in vitro and in vivo functionality. In non-encapsulated islets before and encapsulated islets after shipment, viability was 88.3+/-2.5 and 87.5+/-2.7% (n=6, p=0.30). Stimulation index after static glucose incubation was 5.4+/-0.5 and 6.3+/-0.4 (n=6, p=0.18), respectively. After intraperitoneal transplantation, long-term normoglycemia was consistently achieved with 3,000, 5,000, and 10,000 IEQ encapsulated human islets. When transplanting 1,000 IEQ, mice returned to hyperglycemia after 30-55 (n=4/7) and 160 days (n=3/7). Transplanted mice showed human oral glucose tolerance with lower glucose levels than non-diabetic control mice. Capsules retrieved after transplantation were intact, with only minimal overgrowth. This study shows that human islets maintained the viability and in vitro function after encapsulation and the inhomogeneous alginate-Ca(2+)/Ba(2+) microbeads allow for long-term in vivo human islet graft function, despite long-distance shipment.
BackgroundMinimally invasive pancreaticoduodenectomy (MIPD) was introduced in the attempt to improve the outcomes of the open approach. Laparoscopic pancreaticoduodenectomy (LPD) was first reported by Gagner and Pomp (Surg Endosc 8:408–410, 1994). Unfortunately, due to its complexity and technical demand, LPD never reached widespread popularity. Since it was first performed by P. C. Giulianotti in 2001, Robotic PD (RPD) has been gaining ground among surgeons. MIPD is included as a surgical option in the latest NCCN Guidelines. However, lack of surgical standardization, however, has limited the reproducibility of MIPD and made the acquisition of the technique by other surgeons difficult. We provide an accurate description of our standardized step-by-step RDP technique.MethodsWe took advantage of our 15-year long experience and > 150 cases performed to provide a step-by-step guidance of our RPD standardized technique. The description includes practical “tips and tricks” to facilitate the learning curve and assist with the teaching/evaluation process.Results17 surgical steps were identified as key components of the RPD procedure. The steps reflect the subdivision of the RPD into several parts which help to understand a strategy that takes into accounts specific anatomical landmarks and the demands of the robotic platform.ConclusionsStandardization is a key element of the learning curve of RPD. It can potentially provide consistent, reproducible results that can be more easily evaluated. Despite promising results, full acceptance of RPD as the ‘gold standard’ is still work in progress. Randomized-controlled trials with the application of a standardized technique are necessary to better define the role of RPD.
Human islet isolation outcomes were compared between two purification methods; 32 pancreases were processed by conventional Biocoll purification method (SM, standard method) and 132 pancreases by a refined University of Illinois at Chicago UW/Biocoll method (UIC-UB). There was no difference in donor characteristics between the two study groups. The prepurification equivalent islet number was similar between the groups (359,425+/-40,794 equivalent islet number in SM vs. 370,682+/-17,579 in UIC-UB). SM purified islets were mostly collected in only 2 of 12 fractions (68.9% and 36.3% purity). With the UIC-UB, highly purified islets were collected in 6 of 12 separate fractions (fractions 3-8 with purity of 84.8%, 82.5%, 72.0%, 59.3%, 46.8%, and 36.2%). UIC-UB yielded significantly greater islet yield compared with SM (368,419+/-18,245 vs. 260,908+/-37,835, P=0.017). Islet recovery rate was superior in UIC-UB (84.9% vs. 64.5%, P=0.04). Our study demonstrates a superior recovery of highly pure human pancreatic islets after purification using the refined method of UIC-UB gradient.
Antibody-mediated rejection (AMR) commonly occurs after transplantation of ABO-incompatible and sensitized renal transplant. Treatment regimens commonly include a combination of plasmapheresis (PL) and intravenous immunoglobulin (IVIG). However, some cases of AMR remain refractory to treatment. We report a case series of four patients with AMR refractory to standard therapy (ST) who resolved after splenectomy. Four living donor kidney transplant recipients were diagnosed with AMR. Two patients were ABO incompatible, one was cross-match positive and one had no obvious predisposing factors. After failure of therapy with corticosteroids, PL, IVIG, Thymoglobulin, and Rituximab (three patients) or Campath (one patient), AMR was treated with laparoscopic splenectomy. After an average of 11 days of ST, laparoscopic splenectomy was performed for rescue. The urinary output improved immediately in all patients, serum creatinine levels decreased within 48 hr, and ABO titers fell in the ABO-incompatible patient and the cross-match became negative in the two sensitized patients. Splenectomy may play a role in the treatment of AMR refractory to ST.
Comparative studies between robotic and laparoscopic cholecystectomy (LC) focus heavily on economic considerations under the assumption of comparable clinical outcomes. Advancement of the robotic technique and the further widespread use of this approach suggest a need for newer comparison studies. 676 ICG-aided robotic cholecystectomies (ICG-aided RC) performed at the University of Illinois at Chicago (UIC) Division of General, Minimally Invasive and Robotic Surgery were compiled retrospectively. Additionally, 289 LC were similarly obtained. Data were compared to the largest single institution LC data sets from within the US and abroad. Statistically significant variations were found between UIC-RC and UIC-LC in minor biliary injuries (p = 0.049), overall open conversion (p ≤ 0.001), open conversion in the acute setting (p = 0.002), and mean blood loss (p < 0.001). UIC-RC open conversions were also significantly lower than Greenville Health System LC (p ≤ 0.001). Additionally, UIC ICG-RC resulted in the lowest percentages of major biliary injuries (0 %) and highest percentage of biliary anomalies identified (2.07 %). ICG-aided cholangiography and the technical advantages associated with the robotic platform may significantly decrease the rate of open conversion in both the acute and non-acute setting. The sample size discrepancy and the non-randomized nature of our study do not allow for drawing definitive conclusions.
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