Innovation in organ transplantation: A meeting report

This workshop targeted opportunities to stimulate transformative innovation in organ transplantation. Participants reached consensus regarding the following: (1) Mechanisms are needed to improve the coordination of policy and oversight activities, given overlapping responsibilities for transplantation and clinical investigation among federal agencies. Innovative clinical trials span traditional administrative boundaries and include stakeholders with diverse interests. Participants identified the need for a governmental interagency working group to coordinate nationwide transplant‐related activities. (2) Improvements are required in clinical metrics for transplantation, with alignment of performance goals across transplantation organizations and any development of data requirements being consistent with those goals. Database coordination among clinical centers, organ procurement organizations, regulatory agencies, and payers would facilitate research and better inform policy. New data requirements should provide actionable insights into clinical performance. (3) Innovative research seen as potentially adversely affecting Program‐Specific Reports may reduce centers’ participation. Cutting‐edge research requires mitigation of risk‐aversive behaviors created by reporting of clinical outcomes data. Participants proposed a new review process in advance of implementation of clinical trials to guide “carve‐outs” of transplant center outcomes data from Program‐Specific Reports. Clinical transplantation will be advanced by the development of a shared and comprehensive research agenda to facilitate coordination of research and policy.     

Meniscal transplantation in the human knee: a preliminary report

Meniscectomy can result in degenerative disease, with younger patients developing problems in middle age (1). In addition, loss of a major portion of a medical meniscus may increase instability in an anterior cruciate deficient knee (2). For these two reasons, it is theoretically desirable to transplant menisci in selected patients. In this paper, six patients who underwent allograft transplantation of a meniscus (four medial and two lateral) are presented to demonstrate the apparent success of the operative procedure. Follow-up extends from 24 to 44 months, June 1986 to March 1988. All patients are free of episodes of locking. Four have undergone arthroscopy, which demonstrated healing of the meniscus and no evidence of shrinkage. KT 1,000 values returned to normal in four cases, with concomitant reconstruction of the anterior cruciate ligament (ACL). It is hoped that meniscal transplantation will offset the development of degenerative changes; however, this supposition will remain unproven for decades. Meniscal transplantation seemed to improve stability in the knees undergoing ACL reconstruction. Arthroscopy performed after transplantation revealed that healing does indeed occur. There was no evidence of rejection, confirming the feeling that meniscal tissue is "immunologically privileged." Meniscal transplantation is offered as an adjunct to other reconstructive procedures in cases of meniscal deficient knees.     

Warm ischemia in transplantation: search for a consensus definition

"Warm ischemia" is a term used to describe ischemia of cells and tissues under normothermic conditions. In the transplant setting, this term is used to describe two physiologically distinct periods of ischaemia: (1) Ischemia during implantation, from removal of the organ from ice until reperfusion, and (2) Ischemia during organ retrieval, from the time of cross clamping (or of asystole in non-heart-beating donors), until cold perfusion is commenced. These periods of warm ischemia differ in their nature and the magnitude of their pathophysiologic consequences. In much transplant literature, however, the term "warm ischaemia" is used to describe both of these periods indiscriminately. This paper attempts to produce a definition to distinguish between the two periods of warm ischemia. METHODS: We conducted a questionnaire survey of all UK transplant surgeons. The definitions proposed in the survey were: (a) warm ischemia and re-warm ischemia; (b) first warm ischemia and second warm ischemia; (c) in-situ warm ischemia and ex-vivo warm ischemia; (d) warm ischemia in donor and warm ischemia in recipient; (e) no opinion or other opinion. RESULTS: There was a 64% response rate among 134 consultants with no consensus definition being reached. The majority of consultants (31.4%) preferred the terms "warm ischemia in donor", and "warm ischemia in recipient" to distinguish the two periods. CONCLUSIONS: This paper highlights the need to adopt uniform terms to avoid confusion between different types of warm ischemia in transplantation.     

Three different hepatocyte transplantation techniques for enzyme deficiency disease and acute hepatic failure

The effects of three different techniques of hepatocyte transplantation were investigated: transplantation of free hepatocytes into the spleen and intraperitoneal transplantation of microcarrier-attached hepatocytes or of microencapsulated hepatocytes. The liver-supportive functions of these transplanted hepatocytes were analyzed using either the Gunn rat (hyperbilirubinemia) or rats with acute liver failure. In the Gunn rat intraperitoneal transplantation of microcarrier-attached hepatocytes resulted in a significant reduction of plasma bilirubin for 28 days whereas intraperitoneal transplantation of microencapsulated hepatocytes was ineffective notwithstanding immunosuppression by cyclosporin A. Intrasplenic hepatocyte transplantation was only effective in reducing plasma bilirubin for 14 days. During acute liver failure, liver support was achieved temporarily by hepatocyte transplantation in the spleen, by intraperitoneally transplanted microcarrier-attached hepatocytes, and by microencapsulated hepatocytes to equal extents, the microencapsulated hepatocytes being the least effective after 8 h of liver ischemia.     

补救性肝移植19例手术体会

目的探讨采用补救性肝移植(salvage liver transplantation,SLT)治疗原发性肝细胞癌(肝癌)切除术后肝内复发或肝功能衰竭的疗效及手术体会。方法肝癌切除术后肝内复发16例,肝癌切除术后肝功能衰竭3例,其中合并肾功能异常2例,均接受SLT。术前充分评估病情。手术方式采用附加腔静脉整形的改良背驮式原位肝移植,其中肾功能异常的2例采用股静脉-颈内静脉转流术。肝动脉的重建采用供肝腹腔干动脉与受者肝固有动脉行端端吻合17例,采用供肝腹腔干动脉通过供者髂动脉间置搭桥与受者腹主动脉行端侧吻合2例。胆道的重建全部采用胆道端端吻合。术程始终遵循精细的无瘤操作,术后常规抗排斥和抗感染治疗,并对患者进行了长期随访。结果围手术期19例SLT患者无死亡。术后1、3、5年累积生存率分别为100%、84%、84%;1、3、5年无瘤生存率分别为100%、89%、89%。结论采用SLT治疗肝癌切除术后肝内复发或肝功能衰竭患者的疗效较好。采用腔静脉整形的改良背驮式肝移植术式、充分的术前评估以及遵循精细的无瘤操作是手术成功的关键。     

Outcome measurements in major trauma-Results of a consensus meeting

BackgroundThe NHS Outcomes Framework for England has identified recovery from major injury as an important clinical area. At present, there are no established outcome indicators. As more patients survive major trauma, outcomes will need to be measured in terms of morbidity and not mortality alone.ObjectiveTo make recommendations for a selection of outcome measures that could be integrated into National Clinical Audit data collection and form part of clinical governance requirements for Regional Trauma Networks (RTNs) and measures by which RTNs are held to account by government. Specific focus was given to acute care and rehabilitation for both adults and children.MethodA Multiprofessional, multidisciplinary expert group reviewed the current evidence on outcome measures for major trauma in the adult and children's populations, informed by a systematic review carried out jointly by the Trauma Audit and Research Network (TARN) and the Cochrane Injuries Group. A structured discussion covered functional and quality of life outcome measures as well as patient experience and indicators such as return to work, education and social dependency.ResultsFor the adult population the group agreed with the in-hospital performance and hospital discharge measures recommended in the TARN and Cochrane systematic review. Concerning longer-term outcome indicators, the group suggested the use of the Glasgow Outcome Scale – Extended (GOS-E) and European Quality of Life 5D (EQ-5D) with consideration to be given to the World Health Organisation Quality of Life survey (WHO-QoL). For patients who had ongoing inpatient rehabilitation needs the group thought the measurement of the Rehabilitation Complexity Scale (RCS) and Functional Independence Measure (FIM) were important in total brain injury and, the American Spinal Injury Association Impairment Scale (ASIA) and Spinal Cord Independence Measure (SCIM) in spinal cord injury. For children the group recommended the use of the King's Outcome Scale for Childhood Head Injury (KOSCHI) and Paediatric Quality of Life measure (Peds-QL) preferably at multiple intervals following injury to take into account effects on development.ConclusionSpecific recommendations were made for the use of outcome measures in adults and children with major trauma and those with complex rehabilitation needs following injury. More work on outcome measures in major trauma is needed especially for children. There are currently no robust measures of patient experience for use in major trauma. The importance of data linkage to allow measurement of non-clinical outcomes such as return to work, maintainence of education and societal dependency was emphasised by the group. A system for recording outcomes should be piloted post injury and at 6 and 12 months, with those still requiring inpatient rehabilitation after this time having longer follow up.     

Mycophenolate monitoring in liver, thoracic, pancreas, and small bowel transplantation: a consensus report

Assessing the value of mycophenolic acid (MPA) monitoring outside renal transplantation is hindered by the absence of any trial comparing fixed-dose and concentration-controlled therapy. However, in liver and thoracic transplantation particularly, clinical trials, observational studies with comparison groups, and case series have described MPA efficacy, exposure/efficacy relationships, pharmacokinetic variability, and clinical outcomes relating to plasma MPA concentrations. On the basis of this evidence, this report identifies MPA as an immunosuppressant for which the combination of variable disposition, efficacy, and adverse effects contributes to interindividual differences seemingly in excess of those optimal for a fixed-dosage mycophenolate regimen. Combined with experiences of MPA monitoring in other transplant indications, the data have been rationalized to define circumstances in which measurement of MPA concentrations can contribute to improved management of mycophenolate therapy in nonrenal transplant recipients.     

Frailty in heart transplantation: Report from the heart workgroup of a consensus conference on frailty

A consensus conference on frailty in solid organ transplantation took place on February 11, 2018, to discuss the latest developments in frailty, adopt a standardized approach to assessment, and generate ideas for future research. The findings and consensus of the Frailty Heart Workgroup (American Society of Transplantation's Thoracic and Critical Care Community of Practice) are presented here. Frailty is defined as a clinically recognizable state of increased vulnerability resulting from aging-associated decline in reserve and function across multiple physiologic systems such that the ability to cope with every day or acute stressors is compromised. Frailty is increasingly recognized as a distinct biologic entity that can adversely affect outcomes before and after heart transplantation. A greater proportion of patients referred for heart transplantation are older and have more complex comorbidities. However, outcomes data in the pretransplant setting, particularly for younger patients, are limited. Therefore, there is a need to develop objective frailty assessment tools for risk stratification in patients with advanced heart disease. These tools will help to determine appropriate recipient selection for advanced heart disease therapies including heart transplantation and mechanical circulatory support, improve overall outcomes, and help distinguish frailty phenotypes amenable to intervention.     

两种微囊化肝细胞包裹技术对肝细胞移植疗效影响的实验研究

目的 探讨两种不同微囊化肝细胞包裹技术移植后对急性肝衰鼠的治疗作用.方法 建立急性肝衰大鼠模型,分离纯化SD大鼠肝细胞,应用两种不同的微囊化包裹肝细胞方法 I组(Ba2+-Alg)和Ⅱ组(Alg-P11-Alg),移植后观察其模型鼠肝功能生化指标和存活率.结果 对照组48 h内存活率仅15.4%,I组和Ⅱ组存活率在96 h后始终维持在60%左右.两组对比无显著性差异,并且肝功能生化指标两组对比亦无显著性差异.结论 两种不同微囊化肝细胞包裹方法 ,移植后对急性肝衰鼠具有相同的治疗效果.     

Fracture healing: a consensus report from the International Osteoporosis Foundation Fracture Working Group

Summary

We used the RAND UCLA appropriateness method to decide appropriateness of use of osteoporosis medication after incident fracture and potential for fracture healing and make suggestions for trial design for clinical and preclinical research.

Purpose

To develop appropriateness criteria to assist in the use and study of osteoporosis medications in patients with recent fracture and in the potential use of osteoporosis medications to enhance delayed fracture healing. To promote further research by suggesting preclinical and clinical trial design for studies where fracture healing is the endpoint.

Methods

Design: RAND/UCLA appropriateness method (RUAM). Participants: A panel of experts, both members and non-members of the International Osteoporosis Foundation Fracture Working Group, were identified consisting of geriatricians, rheumatologists, orthopedists, endocrinologists, and internists. This resulted in a round 1 panel of 15 panelists, round 2 panel of 15 members, and a round 3 panel of 14 members. Main outcome measure: Agreement on statements and scenarios using RUAM. Three rounds of voting by panelists took place. Agreement in a third round was reached for 111 statements and scenarios, measured by median panel ratings and the amount of dispersion of panel ratings, based on the interpercentile range.

Results

An expert panel validated a set of statements and scenarios about the use of osteoporosis medications after incident fracture and use of these medications to enhance delayed fracture healing and made recommendations for study designs to investigate the effect of osteoporosis medications on fracture healing.

Conclusions

The result of this exercise is intended to assist in improving patient care by identifying the appropriateness of use of osteoporosis medications after fracture and in fracture healing and to make suggestions for further preclinical and clinical research.

     

Magnetic resonance imaging for the detection, localisation, and characterisation of prostate cancer: recommendations from a European consensus meeting

Background

Multiparametric magnetic resonance imaging (mpMRI) may have a role in detecting clinically significant prostate cancer in men with raised serum prostate-specific antigen levels. Variations in technique and the interpretation of images have contributed to inconsistency in its reported performance characteristics.

Objective

Our aim was to make recommendations on a standardised method for the conduct, interpretation, and reporting of prostate mpMRI for prostate cancer detection and localisation.

Design, setting, and participants

A consensus meeting of 16 European prostate cancer experts was held that followed the UCLA-RAND Appropriateness Method and facilitated by an independent chair.

Measurement

Before the meeting, 520 items were scored for “appropriateness” by panel members, discussed face to face, and rescored.

Results and limitations

Agreement was reached in 67% of 260 items related to imaging sequence parameters. T2-weighted, dynamic contrast-enhanced, and diffusion-weighted MRI were the key sequences incorporated into the minimum requirements. Consensus was also reached on 54% of 260 items related to image interpretation and reporting, including features of malignancy on individual sequences. A 5-point scale was agreed on for communicating the probability of malignancy, with a minimum of 16 prostatic regions of interest, to include a pictorial representation of suspicious foci. Limitations relate to consensus methodology. Dominant personalities are known to affect the opinions of the group and were countered by a neutral chairperson.

Conclusions

Consensus was reached on a number of areas related to the conduct, interpretation, and reporting of mpMRI for the detection, localisation, and characterisation of prostate cancer. Before optimal dissemination of this technology, these outcomes will require formal validation in prospective trials.     

Liver transplantation surgical techniques for extensive retroperitoneal tumor with major blood vessel involvement: a case report

A case of a 71-year-old man with a huge retroperitoneal tumor situated behind the liver, which strongly compressed the liver inferior vena cava (IVC), and gastrointestinal tract is described. With the techniques of whole liver extraction and autologous orthotopic liver transplantation, we successfully removed the tumor. We have the surgical techniques, essential elements, and indications for this procedure.     

原发性肝癌肝移植治疗--我们的共识

原发性肝癌（以下简称肝癌）是我国发病率和病死率最高的恶性肿瘤之一，且有逐年增加的趋势，严重危害人民健康。自从1967年开展首例肝癌肝移植后，经过对适应证的不断探讨和技术改进，目前肝移植已成为治疗肝癌的重要手段之一。