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Organ preservation.

Organ preservation is the supply line for organ transplantation. Currently, the liver, pancreas, and kidney can be successfully preserved for up to two days by flushing the organs with the University of Wisconsin (UW) organ preservation solution and storing them at hypothermia (0-5 degree C). The UW solution is effective because it uses a number of cell impermeant agents (lactobionic acid, raffinose, hydroxyethyl starch) that prevent the cells from swelling during cold ischemic storage. Additionally, the UW solution contains glutathione and adenosine, agents that may stimulate recovery of normal metabolism upon reperfusion by augmenting the antioxidant capacity of the organs (glutathione) or by stimulating high-energy phosphate generation (adenosine) upon reperfusion. Although this method of organ preservation is effective, some organs (5-15% of livers and 20-30% of kidneys) do not function well upon transplant. Injury may be preservation related but may also result from donor and recipient factors that render the organs more susceptible to preservation damage. Results with continuous perfusion of kidneys in the clinics show a reduction in preservation/reperfusion damage. This may be a more appropriate preservation method than cold storage. In this chapter we discuss the development and use of the UW solution and present clinical results. Although intraabdominal organs are well preserved at present, intrathoracic organs (lungs and heart) are less well preserved, and better methods for preservation of these organs are needed for increased use of lung and heart transplantation.

Adenosine↗

[Organ Preservation].

Organ procurement is the first step of organ preservation. We have developed "in situ machine wash out technique with CMH solution" for the purpose of rapid cooling and complete elimination of blood. The utility of this technique was confirmed by both experimentally and clinically. Two major techniques have been used for organ preservation. One is a simple cold storage. Using this method, it is easy to transport organs for transplantation. In addition, availability of UW solution is another advantage of this method. The other is a continuous hypothermic perfusion. Despite of complexity and difficulty of organ transportation, this technique has some advantages, such as viability assay and pretreatment of organs before transplantation. In our experimental studies, viability assays of canine liver and pancreas were achieved using a organ perfusion machine. We also succeeded to prolong the survival of canine pancreatic allograft by pretreatment of anti-Ia antibody during perfusion. While, cryopreservation is most suitable for cell preservation like pancreatic islets. Recently, gene technology was applied for organ preservation studies. In the future, this might become a potent tool for studies in this field.

Cryopreservation↗

[Organ preservation].

Organ preservation is currently performed by simple cold storage or continuous hypothermic perfusion. Cold storage using University of Wisconsin (UW) solution greatly prolongs the successful preservation period for abdominal organs such as the kidney, liver, and pancreas. Thoracic organs (heart, lung), however, can be preserved for only several hours even with UW solution. As a result of improvements in organ transplantation, the number of patients on waiting lists has grown rapidly. Unfortunately, many patients die while waiting for donor organs, and expansion of the donor pool is mandatory. Possible solutions to the shortage of donor organs include the use of marginal donors and non-heart-beating donors. For this purpose, more sophisticated methods of organ preservation are needed, and therefore extensive investigations using current technologies including gene transfer should be performed. Every effort should be made to accommodate the preferences of donors.

Adenosine↗

New concepts in organ preservation.

Organ preservation between donor and recipient is an important link in a chain that ultimately should lead to long term survival of the recipient thanks to a well-preserved, functionally intact organ. The period of organ ischaemia outside the body is subject to a number of biochemical stress factors which become known in more detail as knowledge on biochemical and immunological mechanisms improves. Efficacy of preservation fluids hence reduction of ischaemia injury may become enhanced by such additives as ion channel blockers, enzyme inhibitors, haeme oxygenase modulators, endothelin-l-inhibitors, quenchers of free radicals and anti-apoptotic agents. Many of these compounds, albeit of great theoretical interest, have not (yet?) made their way into clinical practice. This contribution is a survey of some promising agents, concentration and physicochemical interactions of which are analysed in some detail.

Acetylcysteine↗

Trends in organ preservation.

Organ preservation aims to provide a viable graft with primary function post-transplant. The current basis of preservation for transplantation is static cold storage using specific preservation solutions which minimise cellular swelling and membrane pump activity, thus maintaining cellular ATP levels. The current organ shortage and consequent expansion of donor criteria places even greater reliance on minimising graft injury during preservation. This review focuses on current and future advances in preservation technology. The key areas of advance are additives to preservation solutions, alternatives/adjuncts to preservation solutions including perfluorocarbons. A major area of advance is in the modulation of organs during the storage period. This may be achieved by biochemical additives or genetic manipulation. Machine perfusion technology is improving, and this is discussed together with the recent concept of warm (normothermic) perfusion as an alternative means of preservation. The authors provide an overview over the current methods of organ preservation. Cold storage, effective in the short-term is insufficient for marginal organs, does not allow assessment of viability markers, and provokes ischaemic injury. Potential strategies for minimising ischaemic injury include additives to preservation solutions; the two-layer method with perfluorcarbons and UW solution-at present limited to pancreas preservation; organ modulation; organ preconditioning and genetic modification of organs. In particular, the authors illuminate the potential in a reappraisal of the concept of normothermic perfusion.

Cold Temperature↗

Viability assays in organ preservation.

Assays to determine the viability of preserved organs ideally must meet two important requirements: (i) in the clinical environment, they should allow the surgeon to determine if an organ will be viable when it is transplanted (this needs to be done in a noninvasive, nondestructive manner, and currently no such assay exists), and (ii) in the research environment, they should aid in the development of improved methods of organ preservation. Currently, however, the only reliable means of assessing viability is actual transplantation. Many conventional biochemical and physiological techniques have been used to describe the mechanism of preservation-induced injury and to help improve preservation. This paper reviews some techniques that have been used to aid in the development of organ preservation.

Animals↗

The role of oxygen free radicals in organ preservation.

There is controversy over the role of oxygen free radical-induced damage in preserved organs following reperfusion. Furthermore, there has been no definitive study that shows a dramatic improvement in organ functions, delayed graft functions, or improved longevity in organ transplants with oxygen free radical scavenger therapy. However, the presence of glutathione in a new organ preservation solution (University of Wisconsin, UW, solution) yields improved preservation of the liver and heart. The beneficial effect of glutathione may involve in scavenging of cytotoxic products of oxygen metabolism. The results discussed here show that glutathione improves liver preservation. Also, it is shown that glycine, and amino acid component of glutathione, can also give cytoprotection to the rabbit and dog liver tested by either isolated perfusion or orthotopic transplantation. Thus, there may be an involvement of oxygen free radicals in damage to organs hypothermically preserved and transplanted. The injury may occur within the cells or may be due to oxygen within the cells or may be due to oxygen free radicals generated in the extracellular environment.

Adenosine↗

Lactobionic acid as an iron chelator: a rationale for its effectiveness as an organ preservant.

Lactobionic acid, a major constituent of a solution used to preserve organs prior to transplantation, can chelate ferric iron. This is evident by its ability to solubilize iron as well as changes that occur in the UV-VIS spectra of iron in its presence. Relative to iron (III) chelated to EDTA, the lactobionic acid-iron (III) complex is less able to participate in the Fenton reaction as measured by formaldehyde generation from DMSO and bleaching of p-N,N-dimethylnitrosoaniline. Similar effects are seen with citrate and ATP, two substances which also appear to be able to ameliorate ischemia/reperfusion injury. These findings present a rationale for the effectiveness of lactobionic acid as an organ preservant.

Catalysis↗

[Clinical behavior of serous and mucinous borderline tumors of the ovary with diploid DNA stem line. Follow-up studies after organ preserving and non-organ preserving therapy].

Even today, the situation is still unclear with regard to the radicality of the operation and any adjuvant therapy required in treatment of borderline tumors of the ovary. In the last two decades, treatment of these tumors in the Department of Gynecology and Obstetrics at our hospital has depended on the stage of the disease and the age of the patient. It ranged from laparoscopic cyst extirpation to hysterectomy with bilateral adnectomy and omental resection and regional lymphnodectomy. From the end of 1985 to the end of 1992, 35 patients with borderline tumors of the ovaries were operated on. Histologically, 14 borderline tumors were mucinous, 21 were serous. A follow-up investigation was carried out five to 11 years after primary operation. In this period, no patient died of borderline tumor. Twenty-eight patients who were followed up were clinically free of recurrence, five patients are alive, but could not be followed up. Two patients have died of other diseases after five years. Only one patient received adjuvant chemotherapy. She could not be followed up. In the meantime, peritoneal implants were demonstrated at second-look laparoscopies in four out of 18 patients. Later, these could no longer be demonstrated (one patient) or did not affect the survival time (three patients) and thus ultimately was not pathologically relevant. Primarily, two of these four patient had stage Ia-Ic. The paraffin blocks of the preparations are still available from 26 patients, and additional investigations could be carried out. Nineteen percent of the borderline tumors showed micropapillary structures of an MPCS (= micropapillary serous carcinoma), which evidently did not have a negative effect on the prognosis. All borderline tumors showed diploid distributions in DNA cytometry. It is not possible to make a definitive treatment recommendation on the basis of this investigation because the number of patients followed up was too small.

Adult↗

[Organ preservation].

For organ preservation in Europe the Euro-Collins-, UW- and HTK-solution are preferred. While the HTK-solution is mainly used for heart preservation, the UW-solution has shown its advantages for longterm preservation of kidney, liver and pancreas. With regard to renal preservation the HTK-solution provides a higher buffer capacity. According to experimental and theroretical considerations the content of glucose in the Euro-Collins-solution does not seem to correspond to the current state of knowledge. In order to obtain a sufficient primary function renoprotective measurements have proven their efficacy, in addition to an optimal method of organ preservation. Especially in case of suboptimal donors the preservation time should be kept as short as possible.

Animals↗

Influence of 48 hours of cold storage in University of Wisconsin organ preservation solution on metabolic capacity of rat hepatocytes.

BACKGROUND/AIMS: Suspensions of isolated hepatocytes are a valuable tool to study liver functions. For optimal use of the isolated hepatocytes, methods are needed to preserve the hepatocytes while maintaining their viability, metabolic and transport functions. Until now, little has been known about the maintenance of the drug metabolism capacity and energy state, measured by the so-called energy charge (ATP+1/2ADP)/(ATP+ADP+AMP), in hepatocytes after storage in University of Wisconsin cold storage solution (UW). Consequently, we investigated whether UW, originally designed to preserve organs for transplantation, was suitable for preservation of isolated rat hepatocytes with respect to the maintenance of drug metabolism and levels of energy-rich substrates. METHODS: Viability of the isolated rat hepatocytes was determined by trypan blue exclusion, ATP content and energy charge after 24 and 48 h of storage in UW at 0 degrees C. Phase I and II metabolic functions of the cells were studied by measuring the cytochrome P450 content and the metabolic rate of lidocaine and 7-ethoxycoumarin. RESULTS: During 48 h of storage of hepatocytes in UW both phase I and phase II metabolism are preserved at control levels. After storage, the viability of the hepatocytes was not changed significantly, and the cells maintained proper cellular ATP content and overall energy charge. CONCLUSIONS: These results imply that hepatocytes from a single isolation can be stored in UW solution and used for metabolism experiments for 3 consecutive days, allowing a reduction in the use of experimental animals.

Animals↗

Histidine-tryptophan-ketoglutarate solution for organ preservation in human liver transplantation-a prospective multi-centre observation study.

Based on experimental work and clinical small studies, histidine-tryptophan-ketoglutarate (HTK) solution was found to be suitable not only for heart and kidney preservation but also for liver preservation. We decided, therefore, to use this preservation solution for clinical liver preservation in a prospective multi-centre trial. Enrolment to the study was from 1996 to 1999 in four European centres, and the results of 214 patients with HTK-preserved organs were analysed. Analysis showed a primary dysfunction (PDF) rate of 8.8%, with a primary non-function (PNF) rate of 2.3% and initial poor function (IPF) in 6.5%. Patient survival rate at 1 year was 83% and 1-year graft survival rate was 80%. In a univariate and a multivariate analysis PDF, early surgical complications and tendentiously severe infections (septicaemia, pneumonia, cholangitis) were identified as independent risk factors for graft and patient survival. Preservation with HTK can be regarded as an established alternative to preservation with University of Wisconsin (UW) solution when preservation times are short. Definitive assessment of the efficacy of preservation solutions requires further prospective randomised clinical trials that compare HTK and UW.

Drug Therapy, Combination↗

[Prognosis and organ preservation in oropharyngeal cancer treated with radiotherapy].

The records of 102 patients with squamous cell carcinoma of the oropharynx treated at National Sapporo Hospital with external and/or interstitial radiotherapy between 1978 and 1996 were reviewed to evaluate the treatment results, focusing on primary control and functional preservation. Ninety-five patients had been primarily treated with curative intent initially. Of these 95 patients, 4% were in stage I, 19% in stage II, 42% in stage III and 34% in stage IV. Twenty-one patients (22%) had been treated with multidisciplinary chemotherapy, and 19 patients (20%) had been boosted with brachytherapy mainly using Au-198 grains. The cause-specific survival rates at 5 and 10 years were 63% and 52%, respectively. The local control rates at 5 and 10 years were 70% and 51%, respectively. The most important factors affecting local control were the subsite of the primary tumor and N stage. Based on these findings, it is considered that radiotherapy combined with/without chemotherapy except for N3 and the posterior wall type is an effective method of achieving tumor control and preserving organ function, compared with other methods including surgical procedures.

Adult↗

[Practical importance of topography of the main stomach vessels and nerves in performing organ-preserving and organ-sparing operations].

Variations in the structure of vagus nerves studied in 264 organocomplexes of corpses were compared with the data obtained during operations on 122 patients subjected to different modifications of vagotomy. The use of the obtained anatomotopographic picture of the gastric vessels and nerves permitted preserving not only the organ operated upon but also provided the completely undisturbed innervation and blood supply of the stomach and adjacent organs. The results of examination of 176 patients subjected to proximal selective vagotomy and transverse resection of the stomach with the preserved pyloric constrictor showed that at most preserved vascularization and innervation permit to avoid incompetent sutures of anastomosis, its stenosis, dumping syndrome, gastric atonia and diskinesia of biliary ducts.

Adult↗

Organ preservation.

OBJECTIVES: To review organ preservation in cancer treatment within the context of organ function, treatment-related acute and late toxicities, outcome data, and quality of life. DATA SOURCES: Published review and research articles, proceedings of conferences, and oncology textbooks. CONCLUSIONS: The implementation of surgery, with sequential and/or concurrent chemoradiation, has advanced the success of organ preservation in multiple tumor types and organ systems. Integral to the discussion of organ preservation is consideration of quality of life. IMPLICATIONS FOR NURSING PRACTICE: An understanding of organ preservation in cancer treatment will allow oncology nurses to be more effective patient advocates by providing current information that can be integrated into patient care and education.

Anus Neoplasms↗