The use of ex-vivo normothermic perfusion for the resuscitation and assessment of human kidneys discarded because of inadequate in situ perfusion.

BACKGROUND: Many kidneys are rejected for transplantation due to inadequate in situ perfusion during organ retrieval because of the risk of additional ischaemic injury and microvasculature thrombosis. This study describes the use of ex vivo normothermic perfusion (EVNP) for the resuscitation and assessment of human kidneys that were discarded after inadequate in situ perfusion. METHODS: Twenty-two human kidneys were retrieved but then deemed unsuitable for transplantation, primarily due to inadequate in situ perfusion. After a period of static cold storage, kidneys were perfused for 60 min with an oxygenated red cell based solution at 36 °C. RESULTS: Nineteen out of 22 kidneys (86 %) were from DCD donors. During EVNP, kidneys were assessed and scored based on their macroscopic appearance, measures of renal blood flow and urine production. Kidneys were scored from 1 indicating the least injury to 5, indicating the worst. Twelve kidneys had an EVNP score of 1-2, 7 scored 3-4 and 3 kidneys scored 5. The EVNP score 5 kidneys had a low level of tubular function compared to the score 1-4 kidneys. Their perfusion parameters did not improve during EVNP and they were considered non-transplantable. There was no association between the histological evaluation and EVNP parameters. CONCLUSION: EVNP restores function ex vivo and enables an assessment of kidneys that have been declined for transplantation due to inadequate in situ perfusion.

The role of transperineal template prostate biopsies in prostate cancer diagnosis in biopsy naïve men with PSA less than 20 ng ml(-1.).

BACKGROUND: To compare prostate cancer detection rates between transrectal ultrasound (TRUS) prostate biopsy and transperineal template prostate biopsy (TPTPB) in biopsy naïve men. TRUS biopsy is still regarded as gold standard for prostate cancer diagnosis. TPTPB has been shown to improve prostate cancer detection in men with rising PSA and previous negative TRUS biopsies. We carried out a prospective study performing both biopsies in the same group of men with a benign feeling digital rectal examination (DRE), PSA <20 ng ml(-1) and no previous prostate biopsies. METHODS: A total of 50 patients with mean age of 67 years (range: 54-84), mean prostate volume 58 cc (range: 19-165) and mean PSA 8 ng l(-1) (range: 4-18) underwent standard 12-core TRUS biopsy followed immediately by 36-core TPTPB under general anaesthetic. We determined the prostate cancer detection rate between the two diagnostic modalities. RESULTS: In total, 20/50 (40%) had benign pathology. Of 30/50 (60%) diagnosed with prostate cancer, 16 (32%) had positive results in both TRUS and TPTPB, whereas 14 (28%) had negative TRUS but positive TPTPB. No cancers were detected solely by TRUS biopsy. TRUS biopsy detected cancer in 32% versus 60% with TPTPB. In total, 19/30(63%) cancers detected by TPTPB had Gleason score > or =7.2 (4%) experienced urosepsis, 7 (14%) temporary urinary retention, 16 (32%) mild haematuria and 19 (38%) haematospermia. CONCLUSIONS: TPTPB is associated with significantly higher prostate cancer detection rate than TRUS biopsies in biopsy naïve men with a benign feeling DRE and PSA <20 ng ml(-1). PSA appears to be better biomarker than previously thought.

Microwave ablation of the liver: a description of lesion evolution over time and an investigation of the heat sink effect.

AIM: Microwave ablation has been successfully used to treat unresectable liver tumours for many years. However, despite its widespread use, there seems to be a relative paucity of experimental data regarding lesion evolution and the effects of any surrounding vasculature on ablation morphology. The aim of this study was to investigate the principal pathological changes in the liver following microwave ablation, in particular the heat sink effect. In addition we carefully reviewed the available literature to provide an overview of all relevant pathological studies. METHODS: Microwave ablation was carried out on male rats at various distances from the hilum. Histological (H&E) and immunocytochemical (caspase 3) analyses of the lesion were performed at various time points; 0, 4, 24, 48  hours, 2 weeks and 1 month. A literature review was carried out using Medline, Embase and the Cochrane database to identify all relevant histological studies. RESULTS: The lesion underwent complete coagulative necrosis and was extremely regular at the ablation edge with no evidence of any influence from surrounding blood vessels at all time points. H&E and caspase 3 results were consistent and microwave caused little collateral damage outside the intended ablation zone. CONCLUSION: This study suggests that microwave ablation is extremely concise and is minimally affected by the heat sink effect. Comparative investigations with other treatment modalities are required.

Cryotherapy of the liver: a histological review.

INTRODUCTION: Cryotherapy has been largely used in the past for palliation of unresectable liver tumors, but high local recurrence rates and peculiar systemic complications have determined its progressive abandonment. This review analyzes the histological changes produced to provide the basis for the local recurrences. MATERIALS AND METHODS: A detailed literature search was performed on studies focusing on liver cryotherapy. Included were only those that described the histological characteristics in detail. RESULTS: A total of 22 studies were found, one clinical and the others in-vivo animal studies. Similar to other ablative techniques, cryotherapy produces a lesion which is composed by a central zone of coagulative necrosis surrounded with a transitional inflammatory zone. The lesion's dimensions and morphology are influenced by numerous factors including the probe temperature, diameter, the duration of freezing time, fast cooling rate, slow thawing rate, the number of freezing cycles and the inflow occlusion (Pringle maneuver). The temporal evolution is consistent across studies and leads to a progressive inflammatory invasion of the necrosis with definitive fibrotic substitution. CONCLUSIONS: Lesions obtained after cryotherapy seem similar and behave as those obtained after other techniques of liver ablation. However, controversial areas still exist and include the optimum number of freeze thaw cycles, the place of inflow occlusion, the potential corrupting effects of intra-lesional or proximal blood vessels on ablation morphology. The influence of these factors on the local recurrences are still not fully understood.

The effects of vagus nerve stimulation on cognitive performance in patients with treatment-resistant depression.

BACKGROUND: Chronic vagus nerve stimulation (VNS) is effective in the management of treatment-resistant epilepsy. Open-trial evidence suggests that VNS has clinically significant antidepressant effects in some individuals who experience treatment-resistant major depressive episodes. However, limited information regarding the effects of VNS on neurocognitive performance exists. OBJECTIVE: The primary aim of this study was to determine whether VNS leads to neurocognitive deterioration. METHOD: A neuropsychological battery was administered to 27 patients with treatment-resistant depression before and after 10 weeks of VNS. Thirteen neurocognitive tests sampled the domains of motor speed, psychomotor function, language, attention, memory, and executive function. RESULTS: No evidence of deterioration in any neurocognitive measure was detected. Relative to baseline, improvement in motor speed (finger tapping), psychomotor function (digit-symbol test), language (verbal fluency), and executive functions (logical reasoning, working memory, response inhibition, or impulsiveness) was found. For some measures, improved neurocognitive performance correlated with the extent of reduction in depressive symptoms, but VNS output current was not related to changes in cognitive performance. CONCLUSIONS: Vagus nerve stimulation in treatment-resistant depression may result in enhanced neurocognitive function, primarily among patients who show clinical improvement. Controlled investigation is needed to rule out the contribution of practice effects.