APPLICATIONS OF ROBOTIC SURGERY IN ORGAN TRANSPLANTATIONS - APPLICAZIONI DELLA CHIRURGIA ROBOTICA NEI TRAPIANTI D'ORGANO

Introduction: Surgical complications are a major disincentive to transplantation despite the undisputed benefits of restored organ function. Robot-assisted surgery is the new technological advance of the recent years. The da Vinci surgical system, a computer assisted electromechanical device, provides the unique opportunity to test whether laparoscopy can reduce the morbidity in the setting of transplantation. We evaluate the feasibility and safety of this new surgical technique in living kidney donation, kidney transplantation and pancreas transplantation. Materials and methods: Robot assisted living donor nephrectomy was performed on 2 subjects. The immediate post-operative courses for these donors, and their respective recipients, were compared with those of 20 laparoscopic living donor nephrectomies, performed in the same period. Moreover robot assisted kidney transplantation was performed on 2 living kidney recipients and robot assisted laparoscopic pancreas transplantation was performed in further 3 recipients, performing a pancreas after kidney transplant, a simultaneous pancreas kidney transplantation, and a pancreas transplant alone. The grafting procedures were carried out through an 11 mm optic port, two 8 mm operative ports, and a 7 cm incision (midline for pancreas and suprapubic for kidney). The latter was used to introduce the grafts, handle vascular crossclamping, and create pancreas exocrine drainage into the jejunum or uretero-vescical anastomosis in case of kidney transplant. Results: No significant differences between the two donor groups with respect to age, gender, body mass index or renal vasculature were found. The average operative times and the warm ischaemia times were similar. There was no conversion to open surgery in both groups. The estimated blood loss was slight. Following nephrectomy, no complication occurred. The average duration of hospitalization was similar. The estimated creatinine clearance rate was equivalent for all donors, at 5 days and 1 month after nephrectomy. All kidneys started functioning immediately after the transplantation. The mean recipient estimated creatinine clearance was similar. Two kidneys, one from a 56-year-old mother to her 37-year-old daughter and one from a 49-year-old sister to her 48-year-old brother were transplanted laparoscopically using the DaVinci surgical system. Vascular anastomoses were carried out through a total of three additional ports. Surgery lasted 154 and 148 min, including 51 and 39 min of warm ischemia of the graft, respectively. Urine production started immediately after graft reperfusion. Renal function remains optimal at the longest follow-up of 10 and 3 months. The two solitary pancreas transplants lasted 3 and 5 hrs, respectively, the simultaenous pancreas kidney transplantation lasted 8 hrs. Mean warm ischemia time of the pancreas graft was 34 minutes. All pancreata functioned immediately, making their recipients insulin-independent. The kidney graft, revascularized after 35 minutes of warm ischemia, also functioned immediately and fully. No patient had complications during or after surgery; mean hospital stay was 21 ±5 days. After a mean follow-up period of 3.7 months, all recipients are alive with optimal graft function. Conclusion: Robotic assisted living donor nephrectomies were associated with no morbidity among donors, in which both the operative and warm ischaemia times were no longer duration, moreover had no observable adverse effects upon short-term graft function. On the other hand the daVinci surgical system allows the performance of kidney transplantation under optimal operative conditions. Further experience is needed, but it is likely that solid organ transplantation will not remain immune to robotics. We have also shown the feasibility of laparoscopic robot-assisted solitary pancreas and simultaneous pancreas and kidney transplantation. If the safety and feasibility of this procedure can be confirmed in larger series, laparoscopic robot assisted pancreas transplantation could become a new option for diabetics needing beta-cell replacement

Additional modifications to the Blumgart pancreaticojejunostomy: Results of a propensity score-matched analysis versus Cattel-Warren pancreaticojejunostomy

Abstract Background Postoperative pancreatic fistula continues to occur frequently after pancreatoduodenectomy. Methods We have described a modification of the Blumgart pancreaticojejunostomy. The modification of the Blumgart pancreaticojejunostomy was compared to the Cattel-Warren pancreaticojejunostomy in cohorts of patients matched by propensity scores based on factors predictive of clinically relevant postoperative pancreatic fistula, which was the primary endpoint of this study. Based on a noninferiority study design, 95 open pancreatoduodenectomies per group were needed. Feasibility of the modification of the Blumgart pancreaticojejunostomy in robotic pancreatoduodenectomy was also shown. All pancreaticojejunostomies were performed by a single surgeon. Results Between October 2011 and May 2019, there were 415 pancreatoduodenectomies with either a Cattel-Warren pancreaticojejunostomy (n = 225) or a modification of the Blumgart pancreaticojejunostomy (n = 190). There was 1 grade C postoperative pancreatic fistula in 190 consecutive modification of the Blumgart pancreaticojejunostomies (0.5%). Logistic regression analysis showed that the rate of clinically relevant postoperative pancreatic fistula was not affected by consecutive case number. After exclusion of robotic pancreatoduodenectomies (the Cattel-Warren pancreaticojejunostomy: 82; modification of the Blumgart pancreaticojejunostomy: 66), 267 open pancreatoduodenectomies were left, among which the matching process identified 109 pairs. The modification of the Blumgart pancreaticojejunostomy was shown to be noninferior to the Cattel-Warren pancreaticojejunostomy with respect to clinically relevant postoperative pancreatic fistula (11.9% vs 22.9%; odds ratio: 0.46 [0.21–0.93]; P = .03), grade B postoperative pancreatic fistula (11.9% vs 18.3%; P = .18), and grade C postoperative pancreatic fistula (0 vs 4.6%; P = .05) as well as to all secondary study endpoints. The modification of the Blumgart pancreaticojejunostomy was feasible in 66 robotic pancreatoduodenectomies. In this subgroup with 1 conversion to open surgery (1.5%), a clinically relevant postoperative pancreatic fistula occurred after 9 procedures (13.6%) with no case of grade C postoperative pancreatic fistula and a 90-day mortality of 3%. Conclusion The modification of the Blumgart pancreaticojejunostomy described herein is noninferior to the Cattel-Warren pancreaticojejunostomy in open pancreatoduodenectomy. This technique is also feasible in robotic pancreatoduodenectomy

Robot-assisted pancreaticoduodenectomy with vascular resection: technical details and results from a high-volume center

Background: Pancreaticoduodenectomy with vein resection (PD-VR) is widely accepted as a standard procedure to achieve a higher rate of R0 resections in borderline resectable pancreatic tumors. Thanks to the availability of newer technologies, such as the da Vinci Surgical System, several high-volume centers are reporting small series of minimally invasive PD-VR. Methods: A retrospective review of a prospectively maintained database was performed to identify patients who underwent robot-assisted PD-VR (RAPD-VR) between May 2011 and December 2019. The following factors were specifically analyzed: intraoperative results, post-operative complications, mortality at 90 days, patency of vascular reconstructions, overall survival (OS) and disease-free survival (DFS). Results: During the study period 184 patients underwent RAPD, including 22 who received a RAPDVR (12.0%). The superior mesenteric vein was resected in 9 patients (40.9%), the portal vein in 3 patients (13.6%) and the spleno-mesenteric junction in 10 patients (45.5%). Based on the classification provided by the International Study Group on Pancreatic Surgery these procedures were classified as follows: 1 type I (4.5%), 3 type II (13.6%), 10 type III (45.5%) and 8 type IV (36.4%). In no patient the splenic vein was ligated and left behind. The splenic vein was always reimplanted either on the porto-mesenteric axis or in the inferior vena cava. All but one procedure, were completed under robotic assistance (conversion rate 1/22; 4.5%) after a mean operative time of 610.0±83.5 minutes. Median estimated blood loss was 899.7 mL (719.4–1,430.2 mL), with 2 patients (9.1%) receiving intraoperative blood transfusions. Sixteen patients developed post-operative complications (72.7%), graded ≥III (according to Clavien-Dindo) in 5 patients (22.7%). Two patients died within 90 days, accounting for a postoperative mortality of 9.1%. Interestingly, post-operative pancreatic fistula (grade B) occurred in only 1 patient (4.5%). Repeat surgery was required in 4 patients (18.2%) and hospital readmission in 1 patient (4.5%). At the longest available follow-up, vein reconstruction was patent in 19 patients (86.4%). Eighteen patients had a final diagnosis of pancreatic ductal adenocarcinoma (81.8%). After circumferential study of resection margins, microscopic tumor residual ≤1 mm was found in 11 patients (50.0%). The mean number of examined lymph nodes was 42.2 (±16.3), and vascular infiltration was confirmed in 13 patients (59.1%). Median OS was 39.7 (27.5–not available) and DFS 32.9 (11.5–45.8). Tumor recurrence was identified in 6 patients (27.3%). One patient (4.5%) developed isolated local recurrence. Conclusions: We have shown the feasibility of RAPD-VR. The results reported herein need to be confirmed in larger series and their generalizability remains to be established

Refractory CMV infection in post-transplant phase: epidemiological framing in the Italian context, current patient management and unmet needs

Background: Cytomegalovirus (CMV) infection usually occurs asymptomatically but can represent an important cause of morbidity and mortality in patients with compromised immune system such as transplant patients. Infection may not respond to standard therapies leading to refractoriness (with or without resistance) which jeopardizes transplant successful outcome. Objective: Since refractoriness represents a critical point, a project has been conducted to verify the epidemiology in the Italian context and to convey the current patients’ unmet medical needs. Methods: The project included: literature analysis, expert interviews and results’ validation through expert opinion. Based on literature data, a questionnaire was built and submitted to 8 experts with proven experience in the management of post-transplant CMV infection. Topics included epidemiology, patient management, unmet needs and future perspective. Outcomes were validated by 3 additional national experts in solid organ transplantation, hematopoietic stem cell transplantation and infectious diseases. Results: Epidemiological rates from literature applied to current transplantation numbers in Italy estimate approximately 109 adults and 8 children with refractory post-transplant CMV infection in 2021. If valganciclovir/ganciclovir are ineffective, foscarnet is predominantly used. When foscarnet fails, patients have no therapeutic alternatives. Despite being a minority, this represents a high medical need. Therefore, the introduction of new therapeutic options with a better efficacy/safety profile would lead to a significant improvement in refractory CMV infection management. Conclusion: Although refractory infections represent a minority, they are the most critical issue that can occur in post-transplant patients resulting in a high unmet need due to the lack of specific treatment options and the toxicity of current treatments used

The Role of Pathological Method and Clearance Definition for the Evaluation of Margin Status after Pancreatoduodenectomy for Periampullary Cancer. Results of a Multicenter Prospective Randomized Trial

Simple SummaryThere is no clear evidence on the most effective method of pathological analysis and clearance definition (0 vs. 1 mm) to define R1 resection after pancreatoduodenectomy (PD). However, several studies showed that the R1 resection is a poor prognostic factor in patients that have undergone PDs for periampullary cancers. In this randomized clinical trial, specimens were randomized with two pathological methods, the Leeds Pathology Protocol (LEEPP) or the conventional method adopted before the study. The 1 mm clearance is the most effective factor in determining R1 rate after PD but only when adopting the LEEP, the R1 resection represents a significant prognostic factor.Background: There is extreme heterogeneity in the available literature on the determination of R1 resection rate after pancreatoduodenectomy (PD); consequently, its prognostic role is still debated. The aims of this multicenter randomized study were to evaluate the effect of sampling and clearance definition in determining R1 rate after PD for periampullary cancer and to assess the prognostic role of R1 resection. Methods: PD specimens were randomized to Leeds Pathology Protocol (LEEPP) (group A) or the conventional method adopted before the study (group B). R1 rate was determined by adopting 0- and 1-mm clearance; the association between R1, local recurrence (LR) and overall survival (OS) was also evaluated. Results. One-hundred-sixty-eight PD specimens were included. With 0 mm clearance, R1 rate was 26.2% and 20.2% for groups A and B, respectively; with 1 mm, R1 rate was 60.7% and 57.1%, respectively (p > 0.05). Only in group A was R1 found to be a significant prognostic factor: at 0 mm, median OS was 36 and 20 months for R0 and R1, respectively, while at 1 mm, median OS was not reached and 30 months. At multivariate analysis, R1 resection was found to be a significant prognostic factor independent of clearance definition only in the case of the adoption of LEEPP. Conclusions. The 1 mm clearance is the most effective factor in determining the R1 rate after PD. However, the pathological method is crucial to accurately evaluate its prognostic role: only R1 resections obtained with the adoption of LEEPP seem to significantly affect prognosis

Spin injection in the doped bad metal SrTiO3

In this paper, we demonstrate the capability to establish spin-polarized currents in doped SrTiO3 (STO). The results are based on the study of charge and spin transport in STO layers doped by the reversible electromigration of oxygen atoms in resistive-switching La0.7Sr0.3MnO3/STO/Co vertical stacks. The formation of oxygen vacancies inside STO results in a metallic conductivity at temperatures <200–250 K, above which a transitionto an insulating like behavior is detected. A detailed theoretical analysis shows that the behavior of the metallic phase in our samples corresponds to the well-known state of the thermodynamically doped STO featuring the so-called bad metal behavior. Thus, our findings introduce this class of unconventional materials as valuable candidates for innovative spintronic devices

European Society for Organ Transplantation (ESOT) Consensus Statement on the Role of Pancreas Machine Perfusion to Increase the Donor Pool for Beta Cell Replacement Therapy

The advent of Machine Perfusion (MP) as a superior form of preservation and assessment for cold storage of both high-risk kidney’s and the liver presents opportunities in the field of beta-cell replacement. It is yet unknown whether such techniques, when applied to the pancreas, can increase the pool of suitable donor organs as well as ameliorating the effects of ischemia incurred during the retrieval process. Recent experimental models of pancreatic MP appear promising. Applications of MP to the pancreas, needs refinement regarding perfusion protocols and organ viability assessment criteria. To address the “Role of pancreas machine perfusion to increase the donor pool for beta cell replacement,” the European Society for Organ Transplantation (ESOT) assembled a dedicated working group comprising of experts to review literature pertaining to the role of MP as a method of improving donor pancreas quality as well as quantity available for transplant, and to develop guidelines founded on evidence-based reviews in experimental and clinical settings. These were subsequently refined during the Consensus Conference when this took place in Prague.</p

First World Consensus Conference on pancreas transplantation: Part II - recommendations.

Funder: Fondazione Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/100007368Funder: Tuscany Region, Italy; Id: http://dx.doi.org/10.13039/501100009888Funder: Pisa University Hospital, Pisa, ItalyFunder: University of Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/501100007514The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246