José Oberholzer, MD Director Charles O. Strickler Transplant Center Chief, Division of Transplantation Professor of Surgery and Biomedical Engineering
DISCLOSURES No consulting for, no payments, no stocks from any robotic company Before attempting minimal invasive, robotic-assisted kidney and pancreas transplants, I had completed over 500 robotic assisted procedures, and over 200 pancreas transplants and 600 kidney transplants Please, do not replicate without the necessary preparation!
ONE OF FIVE FOUNDING SCIENTISTS AT SIGILON
Founding Scientist UIC Faculty start-up company with the mission to manufacture and distribute human islets under an FDA approved biologic license.
CHICAGO DIABETES PROJECT Founder and coordinator Philanthropic, international collaboration Supported by CELLMATESONTHERUN Foundation
ROBOTICS AND BIOENGINEERING IN TRANSPLANTATION José Oberholzer, MD, MHCM, FACS C.B. Frese and G. Moss Professor of Surgery, Bioengineering and Endocrinology, Chief, Division of Transplantation
OVERVIEW Minimal invasive, robotic-assisted transplant surgery Rationale Current applications Cell Therapy for a functional cure of diabetes Islet transplantation Bioengineering the next generation islet grafts
MINIMAL INVASIVE, ROBOTIC-ASSISTED TRANSPLANT SURGERY
CURRENT APPLICATIONS Pancreatectomy with autologous islet transplantation* Donor Robotic donor nephrectomy* Robotic donor distal pancreatectomy* Robotic right lobe donor hepatectomy* Recipient Robotic kidney transplantation* Robotic pancreas transplantation
WHAT PROBLEM ARE WE ADDRESSING? Surgical access for kidney transplantation in obese patients has a high morbidity. The resulting complications have deleterious effects on both short and long term patient and graft survival. With conventional surgical approaches, most transplant centers deny obese patients access to transplantation
DOES OBESITY IMPACT SURVIVAL ON DIALYSIS?
WHAT IMPACTS GRAFT SURVIVAL?
CORRELATION BETWEEN SSI AND BMI Surgical Site Infections BMI Category
SSI AND GRAFT SURVIVAL Percent Survival Years from Transplant
HYPOTHESIS Minimizing surgical trauma by using robotic technology could reduce wound infections and improve outcomes of kidney transplantation in obese recipients
PRELIMINARY EXPERIENCE To Date >200 cases Matched control study: 28 Obese patients after robotic kidney transplantation completed minimum of 36 months follow up Control Group 28 Obese patients after Open Kidney Transplantation
COMPARISON TO CONTROL Demographics Robotic Transplant (n=28) Control (n=28) p-value Obese (30 BMI<35) 4 4 NS Morbidly Obese (BMI 35) 24 24 NS BMI (kg/m 2 ) 42.6 ± 7.8 38.1 ± 5.4 0.02 Gender (Male) 13 11 NS Age (years) 47.9 ± 10.7 49.8 ± 10.8 NS Diabetic Nephropathy 9 11 NS Crossmatch Positive 7 7 NS ABO Incompatible 1 1 NS Living Donor 26 26 NS Pre-emptive Transplant 9 8 NS
Outcomes Robotic Transplant (n=28) Control (n=28) p-value Cold Ischemia Time (hours) 2.8 ± 3.6 2.0 ± 4.5 NS Warm Ischemia Time (minutes) 47.7 ± 7.8 49.2 ± 25.2 NS Creatinine at 6 months (mg/dl) 1.5 ± 0.4 1.7 ± 0.8 NS Wound Complications 1 8 0.02 Wound Infections 0 8 0.004
POPULATION CHARACTERISTICS (n=143) BMI distribution Ethnicity 45-49 23% 50 11% 30-39 43% Latino 24% Other 2% White 24% 40-44 23% AA 50%
KAPLAN-MEIER SURVIVAL (N=143)
ADJUSTED FIVE-YEAR SURVIVAL ON DIALYSIS Incident dialysis patients & patients receiving a first transplant in the calendar year. All probabilities adjusted for age, gender, & race; overall probabilities also adjusted for primary diagnosis. All ESRD patients, 2005, used as reference cohort. Modality determined on first ESRD service date; excludes patients transplanted or dying during the first 90 days. Five-year survival probabilities noted in parentheses. Dialysis patients followed from day 90 after initiation; transplant patients followed from the transplant date. USRDS 2010 ADR
CONCLUSION Robotic kidney transplantation is an effective approach to reduce wound complications in obese recipients, allowing safe and successful transplantation for patients previously denied access to transplantation.
before 6 months after Provided by Dr. S. Ayloo
Kidney Transplantation BMI 30 kg/m2 BMI < 30 kg/m2 Living donor No living donor Open approach Robotic-assisted approach Wait list Weight loss Combined SG & KT Weight loss KT alone Medical and Surgical approach BMI 30 k/m2 Medical and Surgical approach BMI < 30 k/m2
I believe robotic PTx should be pursued, but it requires a strong commitment. Ciao, Ugo Transplantation. 2012 Jan 27; 93(2):201-6.
SKP: KIDNEY GRAFT SURVIVAL 100.00% 99.00% 98.00% 97.00% 96.00% 95.00% 94.00% 93.00% 92.00% 91.00% 90.00% Jan-10 Jul-10 Jan-11 Jul-11 Jan-12 Observed Expected National
SKP: PANCREAS GRAFT SURVIVAL 100.00% 95.00% 90.00% 85.00% 80.00% Jan-10 Jul-10 Jan-11 Jul-11 Jan-12 Observed Expected National
SKP: PATIENT SURVIVAL 100% 99% 98% 97% 96% 95% 94% Jan-10 Jul-10 Jan-11 Jul-11 Jan-12 Oberved Expected National
FIRST ROBOTIC PAK IN US
FIRST ROBOTIC SPK IN US
COHORT ROBOTIC PANCREAS TX BMI Procedure Drainage EBL (ml) WIT (min) #1 43.9 PAK bladder 200 45 #2 30.1 SPK enteric 150 52 #3 27.8 PTA enteric 150 42 #4 34.8 SPK bladder 150 40 #5 31.6 SPK bladder 200 36
METABOLIC - RESULTS Patien t Pre-Tx HbA1 3 months HbA1c 6 months 12 month Follow up 1 9.7 6.1 6.1 6.0 621 2 9 4.4 4.4 4.8 531 3 7 4.8 4.9 4.9 335 4 12 5.7 4 326 5 6.7 5.4 5.5 259
CONCLUSION Robotic technology can help surgeons providing better care to patients by Minimizing access while preserving dexterity Enhanced virtual reality with new imaging technologies Improving mentoring Robotics has to be used for the betterment of the human condition, and not as a toy or marketing tool for surgeons
ACKNOWLEDGMENTS
CELL THERAPY FOR A FUNCTIONAL CURE OF DIABETES
..among patients, who have a HbA1c 6.9%, the risks of death is twice as high as in the general population and several times as high among patients with poor glycemic control.
ISLET CELL TRANSPLANTATION Islet transplantation may be the most emotionally charged area in diabetes research because its availability would provide the equivalent of a cure, bringing not only freedom from the burdens of injections, glucose testing, and dietary restriction, but even more importantly, protection from the dreaded complications of diabetes. Gordon Weir, Diabetes 1997; 46 (8):1247
OVERVIEW ISLET TRANSPLANTATION Current Status of Islet transplantation How its done Indications Transplant outcomes Bioengineering the next generation islet grafts Islet cell source Immunoprotection
ISLET CELL TRANSPLANTATION
ISLET CELL TRANSPLANTATION
ISLET TRANSPLANTATION BY PORTAL EMBOLIZATION PRE-TX POST-TX
BEFORE
AFTER
CURRENT INDICATIONS FOR ISLET TRANSPLANTATION Islet allo-transplantation with immunosuppression Brittle type I diabetes with hypoglycemic unawareness Type I diabetes with past history of kidney transplantation Autologous islet transplantation without immunosuppression Chronic pancreatitis with indication for total or subtotal pancreatectomy
THE CHALLENGES Only few, selected patients can benefit today in clinical trials Number of human organs suitable and available for transplantation The need for chronic long-term immunosuppression
NEXT GENERATION ISLET GRAFTS: ISLET CELL SOURCES
NEXT GENERATION ISLET GRAFTS: IMMUNOPROTECTION
MICRO-PERIFUSION ON ISLET BIOCHIPS
USE OF MICRO-PERIFUSION ON ENCAPSULATED ISLET BIOCHIPS A C E AUC of [Ca 2+ ] [Ins] glu [Ins] KCI [Ca 2+ ] (F340/380) [Ins] glu [Ins] KCI B D F Fig.5. Impact of microencapsulation process and capsule size on calcium signaling and insulin secretion kinetics. A and B: Glucose induced calcium influx and total AUC. C and D: Glucose-induced insulin secretion and kinetics. E and F: KCI-induced insulin secretion and kinetics. * p<0.05. Veiseh O et al Nat Mater. 2015 Jun;14(6):643-51.
SUMMARY Clinical trials are a success, biological license application in process. Limited to a small patient population Demonstrated proof of concept that human islet cell expansion is feasible and significant advances in other substitute products Next generation islet grafts represent a realistic treatment form for a wider target population
FUNDING SOURCES
UIC ISLET TRANSPLANT TEAM
UIC TRANSPLANT TEAM