Transplantation Surgery Department at IKEM Hospital, Prague, Czech Republic: Increasing Volume and Improving Outcomes Through Innovative Clinical Strategies and Technical Approaches.

BACKGROUND The Czech Republic (CZ), located in central Europe, has a population of 10.5 million with Prague as its capital. Details on the organization of its 7 transplantation (Tx) centers, their procedures, and history have been published before.1 The Institute for Clinical and Experimental Medicine (IKEM), Prague, comprises 2 surgical departments: the Cardiac Surgery Department, performing 40–50 heart Tx annually, and the Transplantation Surgery Department, performing approximately 450 abdominal Tx procedures per year. Since 2011, our department has undergone organizational changes and the implementation of new programs under the leadership of Professor Jiri Fronek.2 Currently, all abdominal Tx procedures in adults and both, adult and pediatric liver transplantations (LTs) take place in our department. Moreover, we also perform general, gastrointestinal, hepato-pancreato-biliary (HPB), bariatric, vascular, and urological surgeries. Twenty-five of 30 surgeons employed in the department, are board certified in either general (abdominal) surgery, vascular surgery, or urology; the department also employs 5 junior fellows. The CZ like many other European countries does not have board certification in Tx surgery. Annual Tx numbers are shown in Figure 1.FIGURE 1.: Transplant volume at the Transplantation Surgery Department, IKEM Hospital, Prague, CZ. The LT program was initiated in 1995. CZ, Czech Republic; DD, deceased donor; IKEM, Institute for Clinical and Experimental Medicine; LD, live donor; LT, liver transplant.ORGAN PROCUREMENTS AND Tx Deceased Donor Retrievals The deceased donors (DD) rate was 25 per million of population in 2021 (IRODaT registry) in the CZ. Each transplant center has its own procurement team/s. At IKEM, we performed 162 DD procurements in 2022, the majority as multiorgan retrievals. DD can be transferred to IKEM, so that challenging procurements, for example, split liver, small bowel, or uterus procurements can be performed on-site. We are prepared of carrying out multiorgan procurements either off-site with the team traveling to the referring hospital or on-site at IKEM. As the team performs both, organ procurements and transplants, timing can therefore be adjusted precisely. The primary benefits of on-site procurements include (1) donor and recipients are in the same facility, (2) the transplant surgeon can choose to perform part of the procurement (eg, split liver), (3) the quality and size of the (liver) graft can be inspected by the recipient surgeon, (4) the LT can be performed immediately after the procurement, and (5) LT can commence in parallel to the DD organ procurement. In cases of off-site procurements, we frequently bring the recipient to the operating room before the return of the procuring surgeons. For on-site procurements, we have been performing bed-side lymph node samplings from the donor groin since June 2019 to have tissue typing and cross-match tests for kidney transplantations (KTs) ready even before commencing with the multiorgan retrieval. These steps, taken by our surgical team, contributed to short cold ischemia times (CITs). During the coronavirus disease (COVID) pandemic, IKEM was not a “COVID” dedicated hospital. IKEM made it a priority to continue its Tx programs to prevent an increase in waiting list mortalities. Most DDs were transferred to IKEM for procurements. Moreover, we treated several patients from other centers that were in need of HPB surgery. With this approach, we were able to assist local intensive care units by freeing up beds for COVID patients. LT There are 2 LT units in the CZ: The Center for Cardiovascular and Transplant Surgery Brno and the IKEM, Prague performing most LTs. Between 1995 and 2022, we performed a total of 2302 LTs: 2290 from DDs and 12 from live donors (LDs). Eighty-nine LTs were combined with KT and 2 LT recipients received a simultaneous heart transplant. Clinical strategies and new techniques have been implemented since 2012 and consist of the following: precisely-timed donor procurement and recipient preparations, minimizing CITs, utilization of all possible transplant techniques and procedures (split grafts, reduced grafts and auxiliary LTs), combined LTs (+ kidney or + heart), split LTs for both pediatric and adult recipients, blood type incompatible (AB0i) LTs for fulminant liver failure (including AB0i partial grafts and AB0i pediatric transplants), donation after circulatory death (DCD) LTs with short CITs, elimination of donor age limits, brisk but meticulous surgical techniques leading to shortened LT-surgery and graft implantation times (ITs), and the implementation of hypothermic oxygenated machine perfusion (HOPE) for extended criteria donor (ECD) livers. In 2022, we also initiated a routine program of LD LTs. Thirteen procedures have been carried out to date: 6 pediatric and 7 adult transplants. Overall Results Outcomes of primary LTs have been analyzed and compared between 2 time periods: from 2001 to 2011 and from 2012 to 2022 (Table 1). The number of LTs almost doubled during those 2 periods while the volume of retransplants increased. Since 2013, there has been a definite trend toward utilizing alternative graft types (especially split livers). Overall, we managed to shorten CITs, LT times, and ITs significantly. Despite using older grafts in older recipients with higher body mass index and higher models for end-stage liver disease scores, we did not observe an increase in primary nonfunction rates, early allograft dysfunction rates, or inferior patient and graft survival rates. TABLE 1. - LTs: data are given as median ± SD LTs Trend 2001–2011 2012–2022 P Statistics Number of all LTs ↑↑ 655 1455 N/A Full size grafts ↓ 634 (96.8%) 1200 (82%) N/A Reduced grafts ↓ 19 (2.9%) 68 (0,5%) N/A Split grafts ↑↑ 2 (0.3%) 187 (13%) N/A Number of first LTs ↓ 634 (97%) 1292 (89%) N/A Donor age (y)a ↑ 39 ± 16 48 ± 17 <0.001 t-test Donor BMI (kg/m2)a ↑ 24 ± 4 26 ± 5 <0.001 t-test Recipient age (y)a ↑ 52 ± 16 57 ± 18 <0.001 Mann-Whitney Recipient BMI (kg/m2)a ↑ 24 ± 4 27 ± 5 <0.001 t-test Cold ischemia time ↓ 5 h:40 min ± 2 h:28 min 4 h:49 min ± 1 h:59 min <0.001 t-test LT-surgery time ↓ 5 h:55 min ± 2 h:27 min 3 h:26 min ± 1 h:13 min <0.001 t-test Graft IT ↓ 37 ± 13 min 24 ± 8 min <0.001 t-test Cirrhosis prevalencea ↓ 68% 48% <0.001 Fisher exact Cancer prevalencea ↑ 13% 27% <0.001 Fisher exact Other diagnosis prevalencea ↑ 13% 18% 0.032 Fisher exact Acute liver failure prevalencea ~ 6% 7% n.s. Fisher exact MELD/Na score in cirrhosisa ↑ 16 ± 6 18 ± 6 <0.001 t-test Pediatric waiting times (d)b ↓ 158 ± 123 53 ± 35 0.014 t-test Primary nonfunctiona ~ 1% 2% 0.25 Fisher exact Early allograft dysfunctiona ~ 20% 22% 0.48 Fisher exact Graft survival 1, 5, 10 y ~ 86%, 79%, 65% 88%, 75%, 57% 0.068 Log-rank Patient survival 1, 5, 10 y ~ 90%, 82%, 71% 94%, 82%, 63% 0.28 Log-rank Bold values are significant, and they are given in the common form “less than” (<). Nonsignificant values are given in absolute values.aCalculated from first LTs.bWe compared the 2001–2012 and 2013–2022 periods as mandatory split LTs were launched in January 2013.BMI, body mass index; IT, implantation time; LT, liver transplantation; MELD/Na, model for end-stage liver diseases-sodium score; N/A, not applicable. Pediatric LT Between 1995 and 2022, we performed 186 LTs in 154 pediatric recipients (<18 y). Since January 2013, we have implemented changes to prevent morbidity and mortality resulting from prolonged waiting times. All children are listed with an urgent status. This forces the on-call surgeon to perform “mandatory” split liver transplants (when there are 2 suitable recipients and the liver graft fulfills center-specific criteria for splitting). Despite the increasing number of referrals and transplants, we have achieved favorable outcomes (1, 5, and 10-y graft survival rates of 76%, 68%, and 66%, respectively; patient survival rates of 89%, 83%, and 81%, respectively) while significantly shortening waiting times (Table 1). DCD LT We perform only controlled DCD, the majority of which fall under Maastricht category III; because the transfer of DCD donors is not permitted, most procurements are performed off-site. The recipient is called in (if not already in-house), and both kidney and liver recipients are fully prepared for Tx at the time the procurement team arrives back at the transplant center. Back-up recipients have also been called in and are ready to go. This strategy ensures an optimized liver graft utilization in addition to a short CIT. Once the procuring team arrives, we transfer the recipient to the operating room, and a hepatectomy procedure is carried out simultaneously with the back-table surgery. We do not use machine perfusion for the DCD LTs; in our setup, this would only cause delays and prolong CITs. We performed 14 DCD LTs between 2016 and 2022. Machine Perfusion for Liver Grafts We have been using the HOPE approach via the portal vein (Liver Assist) for ECD liver grafts since February 2018.3 We do not perform liver graft biopsies to assess the degree of steatosis. A total of 102 livers have been treated with HOPE until 2022. Intestinal and Multivisceral Transplantation We started a program involving intestinal Tx and multi-visceral transplantation (MVT) from DDs in December 2014.4 A total of 13 procedures have been performed to date: 12 full MVTs in addition to one procedure consisting of a small bowel and pancreas transplant. One MVT included a KT, one an auto-KT, and one an abdominal wall Tx. In one MVT, we carried out a split LT. Recipient livers were used for a domino-type LT twice. Three-y survival rate of both grafts and patients was 61.5%. KT Between 1966 and 2022, we performed a total of 6 968 KTs: 6 194 (89%) DDs and 774 (11%) LDs. Of the DD KTs, 718 were simultaneous pancreas/kidney transplants (SPKs), 8 recipients received a simultaneous heart, and 25 simultaneous islet cell transplants. We performed an annual (2001 and 2011) average of 178 KTs from DDs, including KTs in SPKs, in addition to 23 KTs from LDs. These numbers increased to 231 DD KTs and 41 LD KTs annually between 2012 and 2022. The proportion of LD KTs increased from 13% to 17% during the same period. LD nephrectomies are performed through hand-assisted retroperitoneoscopic surgery. Since June 2011, all LD KTs have been performed using this technique and a total of 469 procedures have been carried out by 2 surgeons. In 2011, we launched a national kidney paired exchange program with all donor and recipient surgeries performed at IKEM. We have carried out 14 2-way exchanges, 4 3-way exchanges, 4 4-way exchanges, 2 5-way exchanges, 3 6-way exchanges, and 1 7-way exchange. One open chain was initiated with a bridging donor. A total of 87 LD KPs have been performed between January 2012 and December 2022. We have also established international exchanges with Austria (7 exchanges since September 2016) and Israel (4 exchanges since September 2019). We initiated our kidney DCD program in January 2012, and by 2022, we had performed 70 controlled (Maastricht category III) DCD KTs. Of those, 3 patients died with a functioning graft and 2 were relisted due to graft failure caused by the recurrence of the underlying disease. We also began using the HOPE preservation approach for selected ECD and DCD kidneys in November 2021 and 60 HOPE procedures have been performed until 2022. Kidneys from selected ECDs are considered for dual KTs. Fifty-two such operations have been performed between 2007 and 2022. We have also been implementing a unilateral approach for dual KTs since 2016. In the event of neoplasm formation in the transplanted kidney, we attempt to carry out tumor resection.5 We have successfully accomplished 25 partial graft nephrectomies since 2014 with a preserved renal transplant function. Pancreas Transplantation We have performed an annual average of 38 pancreas transplantations (PTs) during the last 10 y. A total of 841 PTs have been performed since 1983. Procedures are commonly performed as either PT alone, PT after kidney, or SPKs (85%) in qualifying patients with type 1 diabetes. Our surgical approach consists of a right retroperitoneal graft placement (with portal or systemic venous outflow and ileal enteric drainage) through a midline incision since 2010. The Diabetology center is responsible for our islet cell program, and we have performed 128 islet cell transplants Tx between 2005 and 2022. Uterus Transplantation We performed 10 uterus transplantations between 2016 and 2018. Five of those were from DDs and 5 from LDs. An additional 5 DD procurements have been performed as part of the study preparations. We observed 2 early graft losses due to thrombosis, and 3 late losses due to graft dysfunctions and other complications. Three live births of healthy babies have been reported,6 including one from a nulliparous DD7; hysterectomies have been performed electively in those patients. Two recipients continue to have functioning grafts, but are not currently pregnant.8 INTEGRATED PROGRAMS Urology In January 2017, we established a urology section as an integral part of the Tx department to provide in-house urology care mainly to KT candidates and recipients but also to nontransplant patients. The care provided includes a broad spectrum of urological interventions including endoscopic interventions, prostate procedures, nephrectomies (open, laparoscopic, and hand-assisted retroperitoneoscopic surgery), and nephron-sparing surgeries. Bariatric Surgery The bariatric surgery program was initiated in March 2019 primarily for transplant candidates who would otherwise not qualify because of obesity. By 2022, 34 laparoscopic sleeve gastrectomies had been performed, with 17 of them in KT candidates. Of those, 6 have received KTs, and 1 patient an SPK thus far. Vascular Allografts Patients with critical limb ischemia who require an infra-inguinal bypass graft while lacking a suitable autologous saphenous vein are routinely waitlisted for a cold-stored saphenous allograft. Vessels are obtained during multiorgan retrievals. Approximately 20 vascular surgeries using saphenous allografts are performed annually. Thus far, this type of bypass surgery was also performed in a total of 19 limbs of 15 organ transplant recipients with a 1-y-limb salvage rate of 81%.9 Transplant Oncology and Oncovascular Surgery Oncovascular procedures include surgeries intended to remove liver and kidney tumors or removing retroperitoneal metastases of testicular tumors that involve major vessels. During the most recent 10 y, we have carried out 16 thrombectomies of the inferior vena cava because of renal cancer, leiomyosarcoma, or echinococcal disease. An allogeneic vascular patch10 repairing the inferior vena cava was used in 3 patients. Recorded oncology multidisciplinary meetings have been taking place on a weekly basis since 2011. We perform, on average, 300 HPB surgeries per year. In 2022, we also implemented the RAPID concept11 (Resection of segment 2-3 And Partial Liver segment 2-3 transplantation, right portal vein ligation, and Delayed total [residual] right extended hepatectomy) in addition to utilizing LDLT to serve a greater number of patients in need of LT. We have also initiated a pediatric LT program for malignancies in 2011 and an extensive liver surgery program for pediatric malignancies in 2019. A total of 16 LTs and 9 resections (eg, associating liver partition with portal vein ligation for staged hepatectomy—ALPPS, central resections or extended right or left hepatectomies) have been performed to date with all patients listed for a possible rescue LT. None of our patients required an emergency transplant. Virtual Reality, 3D Printing Since May 2021, specialists in information technology have been producing virtual reality (VR) models and 3D prints of organs and their vasculature to assist surgeons in imaging and decision making in preparation of LD LTs (Figure 2), LD KTs, or surgeries for liver malignancies. Approximately 100 such VR models have been created thus far. As an appreciation of their donation, LDs of kidneys and livers receive a 3D printed model of their organ.FIGURE 2.: (A) Living-related liver graft retrieval (right lobe) with the help of (B) VR and (C) 3D printing. VR, virtual reality.RESEARCH In parallel to our clinical efforts, we have a focus on translational and experimental research. Efforts focus on experimental and clinical studies analyzing the uterine vasculature in preparation of uterus transplantation,12,13 and the collection and examination of adipose tissue from living kidney donors utilized for research of atherosclerosis.14 Preclinical research includes monitoring of kidney graft perfusion,15 compromised wound healing in diabetes,16 and tissue engineering of vascular grafts.17 ACKNOWLEDGMENTS The authors thank the following individuals for their valuable contributions to this work: Milos Adamec, Libor Janousek, Pavel Taimr, Pavel Trunecka, Ondrej Viklicky, Ivan Netuka, Eva Kieslichova, Frantisek Saudek, Peter Girman, Petr Wohl, Darina Cupalova, Eva Sticova, Tomas Pantoflicek, David Sibrina, Petr Raska, and the late Miroslav Ryska. The authors are also grateful to Michal Kahle, Tomas Neskudla, Roman Keleman, and Lucie Janeckova for their help with data collection and analysis. Finally, they thank Brian Kavalir for his proofreading services.