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 insulin- independent. 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.
1 January 2008 in Artificial Cells, Blood Substitutes, and Biotechnology
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-Ca2+/Ba2+ microbeads allow for long-term in vivo human islet graft function, despite long-distance shipment.
Minimally 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.
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.
The aim of this study was to clarify whether chemoembolization (TACE) before liver resection (LR) can reduce postoperative hepatocellular carcinoma (HCC) recurrence and improve disease-free and overall survival. Eighty-nine patients with tumor-stage (TNM) I-II HCC were evaluated for LR. Patients were prospectively allocated to LR alone or TACE plus LR based on their place of residence. Twenty nonlocal patients (24%) were selected for LR, while 69 (77.5%) local patients were selected for TACE plus LR. Following TACE, the tumor stage could be confirmed in only 20 patients (29%) who then underwent LR. Operative mortality was 0%, but in the TACE-LR group, 3 patients died of liver failure between 2 and 5 months after surgery. Early recurrence (<24 months) was 59% for LR versus 20% for TACE plus LR (P < .05). Late recurrence was 18% for LR versus 10% for TACE plus LR (P = not significant [NS]). The overall recurrence rate was 76% for LR versus 30% for TACE plus LR (P < .02). Death due to HCC recurrence was 70% for LR versus 15% for TACE plus LR (P < .05). The overall 1- and 5-year survival rates did not differ significantly (71% to 38% for LR v 85% to 43% for TACE + LR; P = NS), whereas the difference in 1- and 5-year disease-free survival was highly significant (64% to 21% for LR v 82% to 57% for TACE + LR; P < .02). TACE was able to improve the HCC staging process and significantly reduce the incidence of early and overall HCC recurrence and related death after LR; it improved the disease-free interval, but not the overall survival, due to an increase in liver failure in the first 5 months.