Safe implementation of robotic right colectomy with intracorporeal anastomosis.

The robotic platform can overcome technical difficulties associated with laparoscopic colon surgery. Transitioning from laparoscopic right colectomy with extracorporeal anastomosis (ECA) to robotic right colectomy with intracorporeal anastomosis (ICA) is associated with a learning phase. This study aimed at determining the length of this learning phase and its associated morbidity. We retrospectively analyzed all laparoscopic right colectomies with ECA (n = 38) and robotic right colectomies with ICA (n = 67) for (pre)malignant lesions performed by a single surgeon between January 2014 and December 2020. CUSUM-plot analysis of total procedure time was used for learning curve determination of robotic colectomies. Non-parametric tests were used for statistical analysis. Compared to laparoscopy, the learning phase robotic right colectomies (n = 35) had longer procedure times (p < 0.001) but no differences in anastomotic leakage rate, length of stay or 30-day morbidity. Conversion rate was reduced from 16 to 3 percent in the robotic group. This study provides evidence that robotic right colectomy with ICA can be safely implemented without increasing morbidity.

Sustained function of alginate-encapsulated human islet cell implants in the peritoneal cavity of mice leading to a pilot study in a type 1 diabetic patient.

AIMS/HYPOTHESIS: Alginate-encapsulated human islet cell grafts have not been able to correct diabetes in humans, whereas free grafts have. This study examined in immunodeficient mice whether alginate-encapsulated graft function was inferior to that of free grafts of the same size and composition. METHODS: Cultured human islet cells were equally distributed over free and alginate-encapsulated grafts before implantation in, respectively, the kidney capsule and the peritoneal cavity of non-obese diabetic mice with severe combined immunodeficiency and alloxan-induced diabetes. Implants were followed for in vivo function and retrieved for analysis of cellular composition (all) and insulin secretory responsiveness (capsules). RESULTS: Free implants with low beta cell purity (19 ± 1%) were non-functional and underwent 90% beta cell loss. At medium purity (50 ± 1%), they were functional at post-transplant week 1, evolving to normoglycaemia (4/8) or to C-peptide negativity (4/8) depending on the degree of beta cell-specific losses. Encapsulated implants immediately and sustainably corrected diabetes, irrespective of beta cell purity (16/16). Most capsules were retrievable as single units, enriched in endocrine cells that exhibited rapid secretory responses to glucose and glucagon. Single capsules with similar properties were also retrieved from a type 1 diabetic recipient at post-transplant month 3. However, the vast majority were clustered and contained debris, explaining the poor rise in plasma C-peptide. CONCLUSIONS/INTERPRETATION: In immunodeficient mice, i.p. implanted alginate-encapsulated human islet cells exhibited a better outcome than free implants under the kidney capsule. They did not show primary non-function at low beta cell purity and avoided beta cell-specific losses by rapidly establishing normoglycaemia. Retrieved capsules presented secretory responses to glucose, which was also observed in a type 1 diabetic recipient.

Human blood outgrowth endothelial cells improve islet survival and function when co-transplanted in a mouse model of diabetes.

AIMS/HYPOTHESIS: As current islet-transplantation protocols suffer from significant graft loss and dysfunction, strategies to sustain the long-term benefits of this therapy are required. Rapid and adequate oxygen and nutrient delivery by blood vessels improves islet engraftment and function. The present report evaluated a potentially beneficial effect of adult human blood outgrowth endothelial cells (BOEC) on islet graft vascularisation and function. METHODS: Human BOEC, 5 × 10(5), were co-transplanted with a rat marginal-islet graft under the kidney capsule of hyperglycaemic NOD severe combined immunodeficiency (SCID) mice, and the effect on metabolic outcome was evaluated. RESULTS: Although vessel density remained unaffected, co-transplantation of islets with BOEC resulted in a significant and specific improvement of glycaemia and increased plasma C-peptide. Moreover, in contrast to control mice, BOEC recipients displayed reduced beta cell death and increases in body weight, beta cell proliferation and graft-vessel and beta cell volume. In vivo cell tracing demonstrated that BOEC remain at the site of transplantation and do not expand. The potential clinical applicability was underscored by the observed metabolic benefit of co-transplanting islets with BOEC derived from a type 1 diabetes patient. CONCLUSIONS/INTERPRETATION: The present data support the use of autologous BOEC in translational studies that aim to improve current islet-transplantation protocols for the treatment of brittle type 1 diabetes.

Human islet cell implants in a nude rat model of diabetes survive better in omentum than in liver with a positive influence of beta cell number and purity.

AIMS/HYPOTHESIS: Intraportal human islet cell grafts do not consistently and sustainably induce insulin-independency in type 1 diabetic patients. The reasons for losses in donor cells are difficult to assess in patients. This study in streptozotocin-diabetic nude rats examines whether outcome is better in an extra-hepatic site such as omentum. METHODS: Intraportal and omental implants of human islet cell grafts with the same beta cell number were followed for function and cellular composition over 5 weeks. Their outcome was also compared with that of rat islet cell grafts with similar beta cell numbers but higher purity. RESULTS: While all intraportal recipients of rat islet cell grafts were normoglycaemic until post-transplant (PT) week 5, none was with human islet cell grafts; loss of human implants was associated with early infiltration of natural killer and CD45R-positive cells. Human islet cell implants in omentum achieved plasma human C-peptide positivity and normoglycaemia in, respectively, nine of 13 and five of 13 recipients until PT week 5; failures were not associated with inflammatory infiltrates but with lower beta cell numbers and purity of the grafts. Observations in human and rat islet cell implants in the omentum suggest that a delayed revascularisation can interfere with their metabolic outcome. Irrespective of normalisation, human omental implants presented beta cell aggregates adjacent to alpha cells and duct cells. CONCLUSIONS/INTERPRETATION: In nude rats, human islet cell implants survive better in omentum than in liver, with positive influences of the number and purity of implanted beta cells. These observations can guide studies in patients.