Tumour growth stimulation after partial hepatectomy can be reduced by treatment with tumour necrosis factor α

This study investigated whether partial hepatectomy enhances the growth of experimental liver metastases of colonic carcinoma in rats and whether treatment with recombinant human tumour necrosis factor (TNF) α can reduce this increased growth. Resection of 35 or 70 per cent of the liver was performed in inbred WAG rats, with sham-operated controls (five to eight animals per group). Immediately after surgery 5·105 CC531 colonic tumour cells were injected into the portal vein. After 28 days the animals were killed and the number of liver metastases counted. A 35 per cent hepatectomy induced a significant increase in the median number of liver metastases (28 versus 3 in controls), whereas a 70 per cent resection provoked excessive growth, consistently leading to more than 100 liver metastases and a significantly increased wet liver weight in all animals. TNF-α was given intravenously to rats following 70 per cent hepatectomy or sham operation in a dose of 160 μg/kg three times per week. This had only a marginal effect on tumour development in sham-operated rats but was very effective following partial hepatectomy (median 45 liver metastases). These observations confirm previous findings that surgical metastasectomy may act as a ‘double-edged sword’ by provoking outgrowth of dormant tumour cells and suggest that adjuvant treatment with TNF-α may be of benefit in patients undergoing resection of metastases

Injection of recombinant tumor necrosis factor directly into liver metastases: an experimental and clinical approach

__Abstract__ Systemic treatment with tumor necrosis factor (TNF) is associated with side-effects, limiting its clinical use in the treatment of malignancies. To investigate the feasibility of other routes of administration experimental and clinical studies were started to establish the toxicity and antitumor activity of TNF after intratumoral (i.t.) injection. In a rat model for colon adenocarcinoma, tumor fragments, implanted subcutaneously or under the hepatic capsule, were treated with TNF injected i.v. or i.t. A dosage of 40 μg/kg was lethal when given i.v., but not i.t. Injection of TNF (40 μg/kg) directly into the tumor resulted in inhibition of tumor growth in the subcutaneous as well as subhepatic tumor model. A phase I study was started in patient

Attitudes among transplant professionals regarding shifting paradigms in eligibility criteria for live kidney donation

Background The transplant community increasingly accepts extended criteria live kidney donors, however, great (geographical) differences are present in policies regarding the acceptance of these donors, and guidelines do not offer clarity. The aim of this survey was to reveal these differences and to get an insight in both centre policies as well as personal beliefs of transplant professionals. Methods An online survey was sent to 1128 ESOT-members. Questions were included about several extended donor criteria; overweight/obesity, older age, vascular multiplicity, minors as donors and comorbidities; hypertension, impaired fasting glucose, kidney stones, malignancies and renal cysts. Comparisons were made between transplant centres of three regions in Europe and between Europe and other countries worldwide. Results 331 questionnaires were completed by professionals from 55 countries. Significant differences exist between regions in Europe in acceptance of donors with several extended criteria. Median refusal rate for potential live donors is 15%. Furthermore, differences are seen regarding pre-operative work-up, both in specialists who perform screening as in preoperative imaging. Conclusions Remarkably, 23.4% of transplant professionals sometimes deviate from their centre policy, resulting in more or less comparable personal beliefs regarding extended criteria. Variety is seen, proving the need for a standardized approach in selection, preferably evidence based

Remarkable changes in the choice of timing to discuss organ donation with the relatives of a patient: a study in 228 organ donations in 20 years

Introduction: We studied whether the choice of timing of discussing organ donation for the first time with the relatives of a patient with catastrophic brain injury in The Netherlands has changed over time and explored its possible consequences. Second, we investigated how thorough the process of brain death determination was over time by studying the number of medical specialists involved. And we studied the possible influence of the Donor Register on the consent rate.Methods: We performed a retrospective chart review of all effectuated brain dead organ donors between 1987 and 2009 in one Dutch university hospital with a large neurosurgical serving area.Results: A total of 271 medical charts were collected, of which 228 brain dead patients were included. In the first period, organ donation was discussed for the first time after brain death determination (87%). In 13% of the cases, the issue of organ donation was raised before the first EEG. After 1998, we observed a shift in this practice. Discussing organ donation for the first time after brain death determination occurred in only 18% of the cases. In 58% of the cases, the issue of organ donation was discussed before the first EEG but after confirming the absence of all brain stem reflexes, and in 24% of the cases, the issue of organ donation was discussed after the prognosis was deemed catastrophic but before a neurologist or neurosurgeon assessed and determined the absence of all brain stem reflexes as required by the Dutch brain death determination protocol.Conclusions: The phases in the process of brain death determination and the time at which organ donation is first discussed with relatives have changed over time. Possible causes of this chang

Preoperative dietary intake of low-dose sulforaphane induces no clinically significant effect in living donor kidney transplantation

Introduction: Sulforaphane (SFN) has anti-inflammatory properties, and is found in broccoli sprouts. Studies suggest that it protects against disease due to its anti-inflammatory activity. The impact of SFN on healthy people undergoing a surgical procedure has not been investigated. Objective: To explore the effect of SFN in living kidney donors on the postoperative inflammatory response and recovery. Methods: We performed a double-blind randomised controlled trial where donors followed a SFN-enriched (8 mg) preoperative diet. Results:A total of 42 donors were included, there were no significant differences at baseline. Postoperative inflammatory response was consistent among both arms and subjective recovery showed no significant difference. Findings regarding postoperative kidney function suggest no consistently significant impact. Discussion: A well-defined SFN-enriched diet did not have anti-inflammatory or a clinically relevant effect on the outcome. Due to the complexity of dietary modification of the inflammatory response, additional research is needed.</p

A novel difficulty grading system for laparoscopic living donor nephrectomy

Background Several difficulty grading systems have been developed as a useful tool for selecting patients and training surgeons in laparoscopic procedures. However, there is little information on predicting the difficulty of laparoscopic donor nephrectomy (LDN). The aim of this study was to develop a grading system to predict the difficulty of LDN. Methods Data of 1741 living donors, who underwent pure or hand-assisted LDN between 1994 and 2018 were analyzed. Multivariable analyses were performed to identify factors associated with prolonged operative time, defined as a difficulty index with 0 to 8. The difficulty of LDN was classified into three levels based on the difficulty index. Results Multivariable analyses identified that male (odds ratio [OR] 1.69, 95% CI 1.37–2.09, P  28 (OR 1.36, 95% CI 1.08–1.72, P = 0.009), pure LDN (OR 1.99, 95% CI 1.53–2.60, P  Conclusion We developed a novel grading system with simple preoperative donor factors to predict the difficulty of LDN. This grading system may help surgeons in patient selection to advance their experiences and/or teach fellows from simple to difficult LDN