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Intestinal transplantation (ITx) is a life-saving procedure for complicated intestinal failure. It is still characterized by a high risk of infection and rejection(1). Of all organs, the intestine is the most vulnerable to ischemia reperfusion injury (IRI) and the associated crosstalk between the innate and adaptive immune response can trigger rejection(2). A crucial factor in limiting IRI is the organ preservation phase. Currently, static cold storage with University of Wisconsin (UW) solution is the gold standard, although other solutions such as HTK (Histidine-Tryptophan-Ketoglutarate) have also been reported (3). Due to low numbers, randomized controlled trials are difficult to organize in this field. ispartof: TRANSPLANT INTERNATIONAL vol:33 issue:8 pages:963-965 ispartof: location:Switzerland status: published

Achtergrond Als totale parenterale voeding (TPV) niet mogelijk is, is een dunnedarmtransplantatie de enige kans op langetermijnoverleving voor patiënten met darmfalen. Maar bij 20-33% van de patiënten treden na een geïsoleerde dunnedarmtransplantatie complicaties van de buikwand op. Casus Wij zagen een 24-jarige vrouw met een kortedarmsyndroom dat werd veroorzaakt door een ernstig gecompliceerd beloop van de ziekte van Crohn. Nadat ze ruim 5 jaar was behandeld met TPV, stelden we de indicatie voor een dunnedarmtransplantatie. Een buikwandtransplantatie was ook nodig vanwege een buikwanddefect, vele littekens van de buikwand en het gebrek aan ruimte in de buik. Patiënte onderging een gecombineerde dunnedarm-buikwandtransplantatie. 6 maanden hierna had ze een sufficiënte buikwand en een niet-afwijkende BMI en had ze geen voedingslijnen meer nodig. Conclusie Deze casus beschrijft de eerste gecombineerde dunnedarm-buikwandtransplantatie in Nederland en in de Eurotransplant-regio bij een patiënte met een eindstadium van darmfalen en met ernstige problemen van de buikwand.

Trials 13, 54 (2012). doi:10.1186/1745-6215-13-54, Published by BioMed Central, London

The cytotoxicity of cisplatin, applied alone or in combination with hyperthermia, to mouse mammary adenocarcinoma cells (M8013S) was studied with the cells either treated in medium [Eagle's minimum essential medium (MEM), supplemented with 10% foetal bovine serum, 100 IU/ml penicillin, 200 mM glutamine and 0.35 g/l NaHCO3] or in Hank's balanced salt solution (HBSS) without serum. To study the role of platinum uptake by the M8013 cells in cytotoxicity, uptake was determined under conditions similar to those used in the survival experiments. Our results show that hyperthermia (30 min at 43 degrees C) enhances the toxicity of cisplatin. Enhanced toxicity by heat treatment is not observed with the cells in HBSS. The thermal enhancement of effects of cisplatin to cells in MEM with serum is clearly related to an enhanced uptake of cisplatin. A novel observation is that in order to obtain a considerable thermal enhancement of the cytotoxic effect of cisplatin, the exposure of the cells to the drug is required not only during the hyperthermic treatment but the exposure has to be maintained for at least 2 h after hyperthermia. These same conditions are also required for enhanced uptake of cisplatin. The present results may indicate that cisplatin has to be bound to some serum component in order to facilitate an 'active' uptake. Hyperthermia leads to a considerable intracellular accumulation of cisplatin, relative to the extracellular concentration. This accumulation takes place during exposure to cisplatin but after heat treatment

Bromodeoxyuridine (BrdUrd)-induced radiosensitization of two different tumour cell lines was compared at equal levels of thymidine replacement. Human lung carcinoma cells (SW-1573) and human colorectal carcinoma cells (RKO) were grown for 48 h in the presence of respectively 1 microM BrdUrd and 4 microM of BrdUrd in order to obtain equal levels of BrdUrd into the DNA. In SW cells the level of thymidine replacement by BrdUrd was 6.7+/-0.5% and in RKO cells this was 7.1+/-0.8. Cell survival after irradiation with single doses up to 8 Gy, was determined with clonogenic assay. The magnitude of BrdUrd-induced radiosensitization was determined by analyzing radiation-dose survival curves with the linear-quadratic formula [S(D)/S(0)=exp-(alphaD+betaD2)]. In the SW cells BrdUrd radiosensitization led to a significant increase of the linear parameter, alpha, determining the initial slope of the survival curves, by a factor of about 2. In the RKO cells BrdUrd increased the value of alpha by a factor 1.4. This suggests that repair of potentially lethal damage (PLD) is inhibited. In both cell lines the quadratic term, beta, strongly influencing the high dose region of the survival curves, was not altered by sensitization by BrdUrd. The increase of alpha is of interest for clinical applications as BrdUrd sensitizes tumour cells after low doses of radiation

Rat spinal cord was locally heated and the expression of heat shock protein with a molecular weight of 72 kDa (HSP72) was investigated. HSP72 was detected in the cord from one of 3 animals 24 h after exposure to 30 min 42.1°C and in all animals (n=11) after 30 min 42.3-42.9°C. Most neurons and glial cells were HSP72 positive. There was agreement in localization between HSP72 and Factor VIII, a surface antigen on the vascular endothelium. Axons were HSP72 negative. The data indicate that spinal cord components that are susceptible to heat injury and thus would benefit from protection by HSP72, such as neurons, glial cells and endothelial cells, do synthesize HSP72 after heat stress.

Experimental data show that nervous tissue is sensitive to heat. Animal data indicate that the maximum tolerated heat dose after local hyperthermia of the central nervous system (CNS) lies in the range of 40-60 min at 42-42 x 5 degrees C or 10-30 min at 43 degrees C. No conclusions concerning the heat sensitivity of nervous tissue can be derived from clinical studies using localized hyperthermia. The choice whether or not to exceed the critical heat dose, as derived from laboratory studies, in clinical practice is very much dependent on the clinical situation such as the anatomical site and volume of the tissue involved, and prior therapy. Data on clinical application of whole body hyperthermia (WBH) show that nervous tissue can withstand a slightly higher heat dose than after localized heating, which might be the result of developing thermal resistance during treatment. Expression of thermotolerance was observed in the spinal cord of laboratory animals. After WBH in man at a maximum between 40 and 43 degrees C for 6 h-30 min CNS complications were reported, but other complications seemed to be more life-threatening. Most studies indicate that impairment of the CNS after WBH was not due to direct heat injury to the brain or spinal cord, but was secondary as a result of physiological changes. Heat, at least if applied shortly after X-rays, enhances the response of nervous tissue to radiation. Neurotoxicity of chemotherapeutic drugs does not seem to be a limiting complication in hyperthermia if combined with chemotherapy, but only few data are available. The limited clinical experience shows that safe hyperthermic treatment of CNS malignancies or tumours located close to the CNS seems feasible under appropriate technical conditions with adequate thermometry and taking the sensitivity of the surrounding normal nervous tissue into account.

The influence of cisplatin on the sensitivity of the rat sciatic nerve to local hyperthermia was investigated. Rats received 1.7 mg/kg cisplatin i.p., twice a week for 6 weeks, up to a cumulative dose of 20.4 mg/kg. After termination of cisplatin treatment, a 5 mm segment of the nerve was locally heated at a temperature of 45 degrees C (5-30 min). Loss of motor function was assessed by means of the toe-spreading test, 24 h post heating. The calculated ED50 for control nerves was significantly (p < 0.01) larger than the ED50 for cisplatin treated rats; 16.3 +/- 1.1 min vs. 10.9 +/- 1.1 min. This indicates that nerves from cisplatin treated rats were more sensitive to heat than nerves from control rats (dose modifying factor = 1.5 +/- 0.2). Histopathological investigation of nerves after heat alone or after heat preceded by cisplatin confirmed these differences and showed that edema, vascular damage and axonal degenerative changes of axons and myelin sheaths occurred at lower heat doses when compared to control nerves. Recovery studies showed that cisplatin treatment before hyperthermia caused a delay in recovery from motor function loss of about 6 days. Cisplatin treatment after hyperthermia had no influence on recovery from motor function loss