Surgical Procurement Research Articles

The Association Between the Origin of the Donation After Circulatory Death Liver Recovery Team and Graft Survival: A National Study

Background. Transplant centers have traditionally relied upon procurement teams from their own programs (transplant program procurement team [TPT]) to recover donation after circulatory death (DCD) livers and rarely use surgical procurement teams not affiliated with the recipient center (nontransplant program procurement team [NTPT]). However, in the era of wider geographic organ sharing, greater reliance on NTPTs is often necessary. Methods. We used national data to study the association between the origin of the donor procurement team (NTPT versus TPT) and the risk of DCD liver allograft failure. Results. Five hundred NTPT and 2257 TPT DCD transplants were identified: 1-y graft survival was 88.9 and 88.6%, respectively (P = 0.962). In a multivariable model, the origin of the procurement team was not associated with graft failure NTPT versus TPT (hazard ratio, 0.92; 95% confidence interval, 0.71-1.22; P = 0.57) but rather with known risks for DCD graft loss including donor age, degree of recipient illness, cold ischemic time, and retransplantation. The overall incidence of retransplantation and ischemic cholangiopathy as an indication for retransplantation were similar between NTPT and TPT. Conclusions. This data suggests that transplant centers may be able to safely use DCD livers recovered by local surgical teams.

A Novel National Program to Maximize Utilization of Heart and Lung Allografts from Donors After Brain Death (DBD) and Donors After Circulatory Death (DCD) for Transplantation

<h3>Purpose</h3> Build a national network of dedicated cardiothoracic surgical procurement and Organ Care System (OCS™) ex-vivo perfusion clinical experts to: Maximize cardiothoracic donor organ utilization for transplantation; overcome logistical and infrastructural burden of distant organ procurements and national allocation; standardize clinical quality of care of ex-vivo perfusion management of cardiothoracic allografts; and establish a better work-life balance for transplant teams across the U.S. <h3>Methods</h3> Leveraging the OCS, the only FDA approved portable perfusion technology for heart and lung transplantation, to build a national infrastructure to enable a turn-key service. This program comprehensively covers: donor screening, donor surgical procurement, OCS perfusion management and transportation of allografts from donor hospitals to any transplant program in the U.S. <h3>Results</h3> The National OCS Program (NOP) was initiated in 2021 for lung transplantation using the OCS Lung technology in 9 major regions across the U.S. Early experience is very encouraging and demonstrated the capabilities of NOP to significantly expand thoracic organ retrieval distance. Enabling cross-country thoracic organ sharing to benefit more patients awaiting transplants while unburdening transplant programs resources. The map below demonstrates actual NOP lung transplants. NOP is now expanding to include OCS Heart and provide similar service to heart transplant programs across the U.S. <h3>Conclusion</h3> The process of cardiothoracic donor organ procurement and related logistics are challenging and unscalable to meet the growing national demand for increased donor organ utilization for lung and heart transplantation. NOP was designed to create a collaborative partnership between industry, OPOs and transplant programs to provide solutions to overcome the existing challenges and transform the field of cardiothoracic transplantation in the U.S.

Contrast-enhanced ultrasonography to evaluate risk factors for short-term and long-term outcomes after liver transplantation: A pilot prospective study

PurposeTo evaluate whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS) can identify liver donation after brain death (DBD) and cardiac death (DCD) with the risk of developing short-term primary graft dysfunction (PGD) or arterial and biliary complications within 1 year. Materials and methodsConsecutive DBD and DCD donors who underwent DUS/CEUS examinations before surgical procurement from February 2016 to June 2018 at our institution were included. The US and CEUS images of each donor liver were analysed, and the parameters were recorded. ResultsThe mean time for US examination was 32 min (range, 20−59 min), and all donors tolerated the examination well. In terms of short-term outcomes, among the 52 eligible donor livers, 20 (38.5 %) of their recipients developed PGD. The multivariable analysis showed that decreased enhancement of donor livers on CEUS (OR = 15.976, 95 % CI: 1.652–154.628, P = 0.017) and high recipient model for end-stage liver disease (MELD) scores (OR = 1.050, 95 % CI: 1.004–1.099, P = 0.034) before liver transplantation (LT) were independent factors of PGD. In contrast, for long-term complications, among the 48 eligible donor livers, 16 (33.3 %) developed arterial or biliary complications within 1 year. The multivariable analysis did not show any independent factors of arterial or biliary complications within 1 year. ConclusionsA decrease in enhancement on CEUS is an independent risk factor for poor short-term outcomes of LT. CEUS may be promising for predicting post-LT outcomes of critically ill donors effectively and safely by evaluating the haemodynamic changes in DBD and DCD donor livers.

Doppler ultrasonography and contrast-enhanced ultrasonography to evaluate liver allograft discard: A pilot prospective study.

Broad hemodynamic changes, is believed to have a profoundly damaging effect on donor livers after brain death (DBD) or cardiac death (DCD). It remains unclear whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS), the imaging modalities to evaluate perfusion, could provide more information of liver discarded. To evaluate the ability of DUS and CEUS to predict the risk of DBD or DCD liver discarded. The consecutive DBD or DCD donors with DUS/CEUS examinations before surgical procurement from February 2016 to June 2018 at our institution were included. The US and CEUS images of each donor liver were analyzed and the parameters were recorded. Among the 67 eligible donor livers, 15 (22.4%) were discarded and 52 (77.6%) were used. The discarded livers showed prolonged SAT of hepatic artery (0.08s vs 0.06s, OR = 2.169, P = 0.008) on DUS, less cases with homogeneous enhancement (40.0% vs 73.1%, OR = 0.243, P = 0.028) on CEUS, more cases with decreased enhancement (53.3% vs 19.2%, OR = 4.800, P = 0.009), and less difference of the peak time between portal vein and liver parenchymal (0.5s vs 6.7s, OR = 0.917, P = 0.034). The multivariable analysis showed that donor liver with prolonged SAT of hepatic artery (OR = 7.304, 95% CI: 1.195-44.655, P = 0.031) and decreased enhancement (OR = 2.588, 95% CI: 1.234-5.426, P = 0.012) were independent factors of liver discarded. DUS/CEUS could be applied as a promising predictive tool to screen high-risk liver donors. The prolonged SAT of hepatic artery on DUS and the decrease of liver donor in enhancement on CEUS, indicating hemodynamic changes in DBD and DCD donor livers, were risk factors of liver discarded.

The effect of inhalational anaesthesia during deceased donor organ procurement on post-transplantation graft survival.

Many deceased by neurologic criteria donors are administered inhalational agents during organ recovery surgery-a process that is characterised by warm and cold ischaemia followed by warm reperfusion. In certain settings, volatile anaesthetics (VA) are known to precondition organs to protect them from subsequent ischaemia-reperfusion injury. As such, we hypothesised that exposure to VA during organ procurement would improve post-graft survival. Lifebanc (organ procurement organisation [OPO] for NE Ohio) provided the investigators with a list of death by neurologic criteria organ donors cared for at three large tertiary hospitals in Cleveland between 2006 and 2016-details about the surgical recovery phase were extracted from the organ donors' medical records. De-identified data on graft survival were obtained from the United Network for Organ Sharing (UNOS). The collated data underwent comparative analysis based on whether or not VA were administered during procurement surgery. Records from 213 donors were obtained for analysis with 138 exposed and 75 not exposed. Demographics, medical histories, and organ procurement rates were similar between the two cohorts. For the primary endpoint, there were no significant differences observed in either early (30-day) or late (five-year) graft survival rates for kidney, liver, lung, or heart transplants. Our findings from this retrospective review of a relatively small cohort do not support the hypothesis that the use of VA during the surgical procurement phase improves graft survival. Reviews of larger datasets and/or a prospective study may be required to provide a definitive answer.

Legislative Enforcement of Nonconsensual Determination of Neurological (Brain) Death in Muslim Patients: A Violation of Religious Rights

Death is defined in the Quran with a single criterion of irreversible separation of the ruh (soul) from the body. The Quran is a revelation from God to man, and the primary source of Islamic knowledge. The secular concept of death by neurological criteria, or brain death, is at odds with the Quranic definition of death. The validity of this secular concept has been contested scientifically and philosophically. To legitimize brain death for the purpose of organ donation and transplantation in Muslim communities, Chamsi-Pasha and Albar (concurring with the US President’s Council on Bioethics) have argued that irreversible loss of capacity for consciousness and breathing (apneic coma) in brain death defines true death in accordance with Islamic sources. They have postulated that the absence of nafs (personhood) and nafas (breath) in apneic coma constitutes true death because of departure of the soul (ruh) from the body. They have also asserted that general anesthesia is routine in brain death before surgical procurement. Their argument is open to criticism because: (1) the ruh is described as the essence of life, whereas the nafs and nafas are merely human attributes; (2) unlike true death, the ruh is still present even with absent nafs and nafas in apneic coma; and (3) the routine use of general anesthesia indicates the potential harm to brain-dead donors from surgical procurement. Postmortem general anesthesia is not required for autopsy. Therefore, the conclusion must be that legislative enforcement of nonconsensual determination of neurological (brain) death and termination of life-support and medical treatment violates the religious rights of observant Muslims.

Campaigning for Organ Donation at Mosques

There is a trend of recruiting faith leaders at mosques to overcome religious barriers to organ donation, and to increase donor registration among Muslims. Commentators have suggested that Muslims are not given enough information about organ donation in religious sermons or lectures delivered at mosques. Corrective actions have been recommended, such as funding campaigns to promote organ donation, and increasing the availability of organ donation information at mosques. These actions are recommended despite published literature expressing safety concerns (i.e., do no harm) in living and end-of-life organ donation. Living donors require life-long medical follow-up and treatment for complications that can appear years later. Scientific and medical controversies persist regarding the international guidelines for death determination in end-of-life donation. The medical criteria of death lack validation and can harm donors if surgical procurement is performed without general anesthesia and before biological death. In the moral code of Islam, the prevention of harm holds precedence over beneficence. Moral precepts described in the Quran encourage Muslims to be beneficent, but also to seek knowledge prior to making practical decisions. However, the Quran also contains passages that demand honesty and truthfulness when providing information to those who are seeking knowledge. Currently, information is limited to that which encourages donor registration. Campaigning for organ donation to congregations in mosques should adhere to the moral code of complete, rather than selective, disclosure of information. We recommend as a minimal standard the disclosure of risks, uncertainties, and controversies associated with the organ donation process.

Impact of adverse pancreatic injury at surgical procurement upon islet isolation outcome.

The consequence of a pancreas injury during the procurement for islet isolation purpose is unknown. The goal of this work was to assess the injuries of the pancreata procured for islet isolation, and to determine their effect on the islet yield. Between January 2007 and October 2013, we prospectively documented every injury of the pancreata processed in our centre for islet isolation. Injuries involving the main duct were classified as major, the others as minor. Donors' characteristics and islet yields were compared between the groups of injuries. A pancreas injury was identified in 42 of 452 pancreata received for islet isolation (9.3%). In 15 cases, the injury was major (3.3% of all pancreata). Although a minor injury did not affect the islet yield, a major injury was significantly associated with unfavourable outcomes (postpurification mean islet equivalent of 364±181, 405±190 and 230±115×10(3) for absence of injury, minor injury and major injury, respectively). A major injury was significantly more prevalent in lean and short donors. We recommend assessing the quality of the pancreas in the islet isolation centre before starting the isolation procedure. Each centre should determine its own policy based on its financial resources and on the wait list.

National guidelines for donation after cardiac death in China

To evaluate whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS) can identify liver donation after brain death (DBD) and cardiac death (DCD) with the risk of developing short-term primary graft dysfunction (PGD) or arterial and biliary complications within 1 year.Consecutive DBD and DCD donors who underwent DUS/CEUS examinations before surgical procurement from February 2016 to June 2018 at our institution were included. The US and CEUS images of each donor liver were analysed, and the parameters were recorded.The mean time for US examination was 32 min (range, 20−59 min), and all donors tolerated the examination well. In terms of short-term outcomes, among the 52 eligible donor livers, 20 (38.5 %) of their recipients developed PGD. The multivariable analysis showed that decreased enhancement of donor livers on CEUS (OR = 15.976, 95 % CI: 1.652–154.628, P = 0.017) and high recipient model for end-stage liver disease (MELD) scores (OR = 1.050, 95 % CI: 1.004–1.099, P = 0.034) before liver transplantation (LT) were independent factors of PGD. In contrast, for long-term complications, among the 48 eligible donor livers, 16 (33.3 %) developed arterial or biliary complications within 1 year. The multivariable analysis did not show any independent factors of arterial or biliary complications within 1 year.A decrease in enhancement on CEUS is an independent risk factor for poor short-term outcomes of LT. CEUS may be promising for predicting post-LT outcomes of critically ill donors effectively and safely by evaluating the haemodynamic changes in DBD and DCD donor livers.

Chitinase-Like Protein Brp-39/YKL-40 Modulates the Renal Response to Ischemic Injury and Predicts Delayed Allograft Function

Kidney hypoperfusion during episodes of systemic hypotension or after surgical procurement for transplantation can lead to tubular cell death via necrosis and apoptosis, which trigger a series of responses that promote repair. The factors that contribute to the repair phase after kidney injury are not well understood. Using a urine proteomic screen in mice, we identified the macrophage-secreted chitinase-like protein Brp-39, the murine protein product of the chitinase 3-like 1 gene, as a critical component of this reparative response that serves to limit tubular cell apoptotic death via activation of Akt, improving animal survival after kidney ischemia/reperfusion. Examination of graded times of renal ischemia revealed a direct correlation between the degree of kidney injury and both Chi3l1/Brp-39 expression in the kidney and its levels in the urine. In samples collected from patients undergoing deceased-donor kidney transplantation, we found higher levels of the orthologous human protein, YKL-40, in urine and blood from allografts subjected to sufficient peri-transplant ischemia to cause delayed graft function than from allografts with slow or immediate graft function. Urinary levels of YKL-40 obtained within hours of transplant predicted the need for subsequent dialysis in these patients. In summary, these data suggest that Brp-39/YKL-40 is a sensor of the degree of injury, a critical mediator of the reparative response, and a possible biomarker to identify patients at greatest risk of sustained renal failure after transplantation.

General Anesthesia for Surgical Procurement in Non-Heart-Beating Organ Donation

To the Editor The Uniform Determination of Death Act defines death as a singular phenomenon by irreversible cessation either of circulatory and respiratory functions or of all brain and brainstem functions.1 Growing demand for transplantable organs has refocused attention on the circulatory standard of declaring death in non-heart-beating donation (NHBD).2 Variable (75 seconds to 5 minutes) cardiac mechanical asystole (or absent arterial pulse) is the United States' circulatory standard.2 This standard is based on expert opinion of zero chance of spontaneous recovery of heart and brain functions after 65 seconds of mechanical asystole.3 Hearts recovered from donors may have normal native mechanical and electrical functions after transplantation3; therefore, mechanical asystole can be reversed. Others conceded that donors in NHBD might not necessarily be dead, either by cardiorespiratory (circulatory standard) or brain (neurological standard) criteria.4 We argued that antemortem and postmortem interventions performed for organ preservation in donors are neuroprotective, preventing rapid deterioration or irreversible cessation of brain functions after mechanical asystole.5 Auyong et al. provided compelling evidence for studying brain function in donors declared dead in NHBD.6 In 3 non-heart-beating donors, the authors demonstrated reproducible surges in Bispectral Index scores from real-time electroencephalograms. Chawla et al.7 reported similar Bispectral Index score surges in 7 cases within minutes after being declared dead, i.e., pulseless, motionless, and asystolic on the electrocardiogram. The clinical and neurological significance of delayed surges of brain electric activity after mechanical asystole is unknown. However, nocioception and awareness are real concerns during surgical procurement in NHBD. General anesthesia is not administered to donors because they are assumed dead with no discernable brain functions. This is of particular concern because age eligibility for NHBD starts from newborn and includes donors with normal brain function before sustaining mechanical asystole (e.g., end-stage musculoskeletal disease, pulmonary disease, and high spinal cord injury) (available at http://optn.transplant.hrsa.gov/policiesAndBylaws/bylaws.asp; accessed March 20, 2010).8 We agree with Auyong et al. that donors should be routinely monitored with electroencephalogram for dosing of anesthetic and opioids drugs during surgical procurement. Mohamed Y. Rady, MD, PhD, FCCM Joseph L. Verheijde, PhD, MBA, PT Department of Critical Care Medicine Departments of Biomedical Ethics, Physical Medicine, and Rehabilitation Mayo Clinic Phoenix, Arizona School of Life Sciences Center for Biology and Society Arizona State University Tempe, Arizona [email protected]

Insulin expressed from endogenously active glucose-responsive EGR1 promoter in bone marrow mesenchymal stromal cells as diabetes therapy

Advances in islet transplantation have encouraged efforts to create alternative insulin-secreting cells that overcome limitations associated with current therapies. We have recently demonstrated durable correction of murine and porcine diabetes by syngeneic and autologous implantation, respectively, of primary hepatocytes non-virally modified with a glucose-responsive promoter-regulated insulin transgene. As surgical procurement of hepatocytes may be clinically unappealing, we here describe primary bone marrow-derived mesenchymal stromal cells (BMMSC) as alternative insulin-secreting bioimplants. BMMSC are abundant and less invasively procured for clinical autologous transplantation. Electroporation achieved high transgene transfection efficiencies in human BMMSC (HBMMSC) and porcine BMMSC (PBMMSC). We transcriptomically identified an HBMMSC glucose-responsive promoter, EGR1. This endogenously active promoter drove rapid glucose-induced transgene secretions in BMMSC with near-physiological characteristics during static and kinetic induction assays simulating normal human islets. Preparatory to preclinical transplantation, PBMMSC transfected with the circular insulin transgene vector or stably integrated with the linearized vector were evaluated by intrahepatic or intraperitoneal xenotransplantation in streptozotocin-diabetic and non-diabetic NOD-SCID mice. Hyperglycemia, glucose tolerance and body weight were corrected in a dose-responsive manner. Hypoglycemia was not observed even in identically implanted non-diabetic mice. These results establish human EGR1 promoter-insulin construct-modified BMMSC as safe and efficient insulin-secreting bioimplants for diabetes treatment.

Radiogenomics: Creating a link between molecular diagnostics and diagnostic imaging

Studies employing high-throughput biological techniques have recently contributed to an improved characterization of human cancers, allowing for novel sub-classification, better diagnostic accuracy, and more precise prognostication. However, requirement of surgical procurement of tissue among other things limits the clinical application of such methods in everyday patient care. Radiographic imaging is routine in clinical practice but is currently histopathology based. The use of routine radiographic imaging provides a potential platform for linking specific imaging traits with specific gene expression patterns that inform the underlying cellular pathophysiology; imaging features could then serve as molecular surrogates that contribute to the diagnosis, prognosis, and likely gene-expression-associated treatment response of various forms of human cancer. This review focuses on high-throughput methods such as microarray analysis of gene expression, their role in cancer research, and in particular, on novel methods of associating gene expression patterns with radiographic imaging phenotypes, known as “radiogenomics.” These findings underline a potential future role of both diagnostic and interventional radiologists in genetic assessment of cancer patients with radiographic imaging studies.

Statistics don't count

Kidney hypoperfusion during episodes of systemic hypotension or after surgical procurement for transplantation can lead to tubular cell death <i>via</i> necrosis and apoptosis, which trigger a series of responses that promote repair. The factors that contribute to the repair phase after kidney injury are not well understood. Using a urine proteomic screen in mice, we identified the macrophage-secreted chitinase-like protein Brp-39, the murine protein product of the <i>chitinase 3-like 1</i> gene, as a critical component of this reparative response that serves to limit tubular cell apoptotic death <i>via</i> activation of Akt, improving animal survival after kidney ischemia/reperfusion. Examination of graded times of renal ischemia revealed a direct correlation between the degree of kidney injury and both <i>Chi3l1</i>/Brp-39 expression in the kidney and its levels in the urine. In samples collected from patients undergoing deceased-donor kidney transplantation, we found higher levels of the orthologous human protein, YKL-40, in urine and blood from allografts subjected to sufficient peri-transplant ischemia to cause delayed graft function than from allografts with slow or immediate graft function. Urinary levels of YKL-40 obtained within hours of transplant predicted the need for subsequent dialysis in these patients. In summary, these data suggest that Brp-39/YKL-40 is a sensor of the degree of injury, a critical mediator of the reparative response, and a possible biomarker to identify patients at greatest risk of sustained renal failure after transplantation.

Small intestinal submucosa improves islet survival and function duringin vitroculture

To evaluate the recovery and function of isolated rat pancreatic islets during in vitro culture with small intestinal submucosa (SIS). Pancreatic islets were isolated from Wistar rats by standard surgical procurement followed by intraductal collagenase distension, mechanical dissociation and Euroficoll purification. Purified islets were cultured in plates coated with multilayer SIS (SIS-treated group) or without multilayer SIS (standard cultured group) for 7 and 14 d in standard islet culture media of RPMI 1640. After isolation and culture, islets from both experimental groups were stained with dithizone and counted. Recovery of islets was determined by the ratio of counts after the culture to the yield of islets immediately following islet isolation. Viability of islets after the culture was assessed by the glucose challenge test with low (2.7 mmol/L) and high glucose (16.7 mmol/L) solution supplemented with 50 mmol/L 3-isobutyl-1-methylxanthine (IBMX) solution. Apoptosis of islet cells after the culture was measured by relative quantification of histone-complexed DNA fragments using ELISA. After 7 or 14 d of in vitro tissue culture, the recovery of islets in SIS-treated group was significantly higher than that cultured in plates without SIS coating. The recovery of islets in SIS-treated group was about twice more than that of in the control group. In SIS-treated group, there was no significant difference in the recovery of islets between short- and long-term periods of culture (95.8+/-1.0% vs 90.8+/-1.5%, P>0.05). When incubated with high glucose (16.7 mmol/L) solution, insulin secretion in SIS-treated group showed a higher increase than that in control group after 14 d of culture (20.7+/-1.1 mU/L vs 11.8+/-1.1 mU/L, P<0.05). When islets were placed in high glucose solution containing IBMX, stimulated insulin secretion was higher in SIS-treated group than in control group. Calculated stimulation index of SIS-treated group was about 23 times of control group. In addition, the stimulation index of SIS-treated group remained constant regardless of short- and long-term periods of culture (9.5+/-0.2 vs 10.2+/-1.2, P>0.05). Much less apoptosis of islet cells occurred in SIS-treated group than in control group after the culture. Co-culture of isolated rat islets with native sheet-like SIS might build an extracellular matrix for islets and provide possible biotrophic and growth factors that promote the recovery and subsequent function of islets.

Improved islet survival and in vitro function using solubilized small intestinal submucosa.

In vitro proliferation of isolated pancreatic islets has become an area of great interest given the scarcity of clinical islet donors and the islet mass requirements for clinical islet transplantation. Small intestinal submucosa (SIS), a naturally occurring extracellular matrix, has been investigated to promote wound healing, tissue remodeling and cell growth. This study evaluated recovery and function of isolated canine pancreatic islets following in vitro tissue culture. Pancreatic islets were isolated from mongrel dogs using standard surgical procurement followed by intraductal collagenase distension, mechanical dissociation and EuroFicoll purification. Groups of purified islets were cultured in a humidified atmosphere of 95% air and 5% CO(2) for 48 hours in standard islet culture conditions of CMRL 1066 tissue culture media (Gibco) which had been supplemented with 25microM HEPES, penicillin/streptomycin and either 10% heat inactivated fetal calf serum (FCS, Gibco) or solubilized SIS solution (Cook Biotech, Inc., West Lafayette, IN). The mean recovery of islets following the culture period was determined by sizing duplicate counts of a known volume and viability was assessed by static incubation with low glucose (2.8 mM), high glucose (20 mM) and high glucose solution supplemented with 50 microm IBMX solution. Remaining islets were embedded histologically. From a consecutive series of six culture experiments, a significantly higher (p < 0.05) recovery of islets co-cultured with SIS was observed when compared to controls. Mean islet recovery was 84.5 +/- 2.9% (mean +/- SEM) from the SIS cultured group compared with 64.7 +/- 4.5% from the control group cultured in FCS (p < 0.05, n=6). Islets from the SIS treated group exhibited a significantly higher (p <, 0.05) insulin response to the high glucose stimulus than islets cultured in the standard FCS cultured solution. The calculated stimulation index was 12.3 +/- 3.4 for the SIS-treated group compared with 5.6 +/- 1.8 for the standard cultured group (p < 0.05). The overall mean numbers of islets recovered following in vitro culture was also higher in the SIS-treated group. The proportion of islets with a mean diameter >150 microm increased from 24% to 31% in the SIS-treated group, whereas the same proportion decreased to 18% from 22% in the control (FCS-treated) group. Histological evaluation of fixed tissue samples collected following the culture period identified insulin and glucagon-secreting cells in the SIS and FCS treated groups, however a higher frequency of insulin positive cells were detected consistently in the SIS treated group. A proliferation marker (PCNA) identified positive cells within both groups as well. This study suggests that co-culture of freshly isolated canine islets in medium supplemented with solubilized SIS can improve the post-culture recovery and in vitro islet function. Future investigations will focus on the cellular interactions of SIS, both in vitro and in vivo.

HUMAN ISLET ISOLATION IN 104 CONSECUTIVE CASES

One of the major steps toward successful islet transplantation for the treatment of type diabetes is to obtain islets of sufficient number and viability. Using a standardized method of isolating islets, the goal of this study was to analyze the factors influencing the outcome of islet isolation. A total of 104 cadaveric human pancreata were processed for islets by the same team. Data from the islet-processing charts were reviewed retrospectively. The two endpoints were the recovery of islets, viable after 2 days of culture (group V = viable, group NV = nonviable) and the islet yield. Viable islets were recovered in 61% of cases (n = 63). Minimal blood glucose recorded during hospitalization was very significantly lower in group V (124 +/- 5 vs. 148 +/- 9, P = 0.01). Lack of significant medical history in the donor was associated with better viability as compared with various donor predispositions (chi-2 4.21, P = 0.04). Cold ischemia time (8.1 +/- 0.5 hr in group V vs. 9.8 +/- 0.9 hr in group NV, P = 0.07) and collagenase lot (5 lots tested, chi-2 13.1, P = 0.01) also affected the recovery of viable islets. Hospital time was shorter in group V (65.3 +/- 6.8 vs. 80.9 +/- 17.9 hr, P = 0.35). Multivariate logistic regression analyses of viable islet recovery identified minimal blood glucose (P = 0.03) and collagenase lot (P = 0.06) as the most significant risk factors. However, the best multivariate predictive model--which includes blood glucose, collagenase lot, donor age and surgical procurement team--correctly predicted 66.2% of cases only. Multivariate analysis of final islet yield designed hospitalization length, cardiorespiratory arrest, surgical procurement team, and collagenase lot as the best predictors. These data obtained in a large series of pancreata emphasized several donor and technical factors that should target the attention of islet transplant researchers in order to improve islet yield and viability.

HUMAN ISLET ISOLATION IN 104 CONSECUTIVE CASES

One of the major steps toward successful islet transplantation for the treatment of type diabetes is to obtain islets of sufficient number and viability. Using a standardized method of isolating islets, the goal of this study was to analyze the factors influencing the outcome of islet isolation. A total of 104 cadaveric human pancreata were processed for islets by the same team. Data from the islet-processing charts were reviewed retrospectively. The two endpoints were the recovery of islets, viable after 2 days of culture (group V = viable, group NV = nonviable) and the islet yield. Viable islets were recovered in 61% of cases (n = 63). Minimal blood glucose recorded during hospitalization was very significantly lower in group V (124 +/- 5 vs. 148 +/- 9, P = 0.01). Lack of significant medical history in the donor was associated with better viability as compared with various donor predispositions (chi-2 4.21, P = 0.04). Cold ischemia time (8.1 +/- 0.5 hr in group V vs. 9.8 +/- 0.9 hr in group NV, P = 0.07) and collagenase lot (5 lots tested, chi-2 13.1, P = 0.01) also affected the recovery of viable islets. Hospital time was shorter in group V (65.3 +/- 6.8 vs. 80.9 +/- 17.9 hr, P = 0.35). Multivariate logistic regression analyses of viable islet recovery identified minimal blood glucose (P = 0.03) and collagenase lot (P = 0.06) as the most significant risk factors. However, the best multivariate predictive model--which includes blood glucose, collagenase lot, donor age and surgical procurement team--correctly predicted 66.2% of cases only. Multivariate analysis of final islet yield designed hospitalization length, cardiorespiratory arrest, surgical procurement team, and collagenase lot as the best predictors. These data obtained in a large series of pancreata emphasized several donor and technical factors that should target the attention of islet transplant researchers in order to improve islet yield and viability.

An emerging cancer risk

Advancements in surgical techniques, procurement, and immunosuppressant therapy have made organ transplantation a major treatment modality with increasing survival posttransplantation. However, this longevity has placed individuals with transplanted organs at an increased risk for developing cancer. This article examines the following pertinent issues. First, what is the prevalence of malignancies among transplant recipients? Second, are organ recipients told that they may be at risk for developing cancer? Third, is the medical community trading one lethal disease for another? And finally, are oncology nurses properly trained to handle the maintenance of a transplanted organ while caring for a person with cancer? This article looks at several ethical issues, including the ethical principle of autonomy, which examines the respect for a patient's right to choose or refuse treatment. Within this text, autonomy will be the basis for informed consent and the need for cancer risk disclosure. The ethical principle of beneficence is also examined, in regards to the health-care community trading one illness for another. The final ethical principle of nonmaleficence is considered and the need for future oncology nurses to examine their practice to determine if they are ready to care for these posttransplant cancer patients.

Reconstructive Hip Prosthesis Surrounded by Allografts

Autologous grafts, unlike allogenic grafts, have an important osteogenic potential. But, as the procurement volume is limited, they do not permit bone or joint reconstruction where there has been partial or total resection as a result of either a bone tumor or post-traumatic lack of substance. For this reason, we have elected since 1976 to use fresh allogenic bone grafts and since 1981 deep-frozen allogenic grafts to rebuild the skeleton (421 cases, 1976-1990). Deep-freezing alone allows the preservation of even large bone pieces in satisfactory conditions of sterilization. This type of preservation keeps the bone architecture in an optimal biological and biomechanical state. With the bone cells destroyed and the bone being recolonized by the host's own cells, there is no immunological risk of inadequate blood and leukocyte compatibility between donor and recipient. If the bone is to be totally or partially integrated by the skeleton within a few years, the functional value of the cartilaginous surfaces can be altered after a massive osteocartilaginous graft. At the hip therefore we prefer to use a massive prosthesis surrounded by allografts.Reconstructive hip prosthesis surrounded by deep-frozen preserved bone has several advantages: easy fixation of the muscles on the graft; close tightening of the muscles; increasing of the bone mass; rapid loading.Since 1983, 103 hips have been rebuilt with cortico-spongious allografts (femoral heads, total hemipelvis or acetabulum) associated with total hip prosthesis. To reconstruct the upper part of the femur we used a mega hip prosthesis surrounded by allograft. The reconstructive mega hip prosthesis has to have the inner shape of the femur with its two sagittal curves to permit cement less fixation at the upper part of the prosthesis which is placed into the allograft and cemented fixation of the lower part of the stem which is fixed into the receiver bone.When great precautions are taken during surgical procurement and grafting (sterility, stability, and appropriate muscular surrounding) the long-term results are excellent in 80% of cases.