Hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy: HARP-trial

Contains fulltext : 88436.pdf (publisher's version ) (Open Access)BACKGROUND: Transplantation is the only treatment offering long-term benefit to patients with chronic kidney failure. Live donor nephrectomy is performed on healthy individuals who do not receive direct therapeutic benefit of the procedure themselves. In order to guarantee the donor's safety, it is important to optimise the surgical approach. Recently we demonstrated the benefit of laparoscopic nephrectomy experienced by the donor. However, this method is characterised by higher in hospital costs, longer operating times and it requires a well-trained surgeon. The hand-assisted retroperitoneoscopic technique may be an alternative to a complete laparoscopic, transperitoneal approach. The peritoneum remains intact and the risk of visceral injuries is reduced. Hand-assistance results in a faster procedure and a significantly reduced operating time. The feasibility of this method has been demonstrated recently, but as to date there are no data available advocating the use of one technique above the other. METHODS/DESIGN: The HARP-trial is a multi-centre randomised controlled, single-blind trial. The study compares the hand-assisted retroperitoneoscopic approach with standard laparoscopic donor nephrectomy. The objective is to determine the best approach for live donor nephrectomy to optimise donor's safety and comfort while reducing donation related costs. DISCUSSION: This study will contribute to the evidence on any benefits of hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy. TRIAL REGISTRATION: Dutch Trial Register NTR1433

Impairment of cognitive functioning during Sunitinib or Sorafenib treatment in cancer patients: a cross sectional study

Impairment of cognitive functioning has been reported in several studies in patients treated with chemotherapy. So far, no studies have been published on the effects of the vascular endothelial growth factor receptor (VEGFR) inhibitors on cognitive functioning. We investigated the objective and subjective cognitive function of patients during treatment with VEGFR tyrosine kinase inhibitors (VEGFR TKI). Three groups of participants, matched on age, sex and education, were enrolled; 1. metastatic renal cell cancer (mRCC) or GIST patients treated with sunitinib or sorafenib (VEGFR TKI patients n = 30); 2. patients with mRCC not receiving systemic treatment (patient controls n = 20); 3. healthy controls (n = 30). Sixteen neuropsychological tests examining the main cognitive domains (intelligence, memory, attention and concentration, executive functions and abstract reasoning) were administered by a neuropsychologist. Four questionnaires were used to assess subjective cognitive complaints, mood, fatigue and psychological wellbeing. No significant differences in mean age, sex distribution, education level or IQ were found between the three groups. Both patient groups performed significantly worse on the cognitive domains Learning & Memory and Executive Functions (Response Generation and Problem Solving) compared to healthy controls. However only the VEGFR TKI patients showed impairments on the Executive subdomain Response Generation. Effect sizes of cognitive dysfunction in patients using VEGFR TKI were larger on the domains Learning & Memory and Executive Functions, compared to patient controls. Both patients groups performed on the domain Attention & Concentration the same as the healthy controls. Longer duration of treatment on VEGFR TKI was associated with a worse score on Working Memory tasks. Our data suggest that treatment with VEGFR TKI has a negative impact on cognitive functioning, specifically on Learning & Memory, and Executive Functioning. We propose that patients who are treated with VEGFR TKI are monitored and informed for possible signs or symptoms associated with cognitive impairment. ClinicalTrials.gov Identifier: NCT0124684

Reduction of treatment volume and radiation doses to surrounding tissues with intraprostatic gold markers in prostate cancer radiotherapy

Contains fulltext : 96271.pdf (publisher's version ) (Closed access)BACKGROUND: High-precision radiotherapy with gold marker implantation is a standard technique for prostate cancer treatment. To provide insight into the beneficial effect of gold markers, the influence on treatment volume and radiation doses to healthy tissues was investigated. PATIENTS AND METHODS: Three consecutive treatment margins were constructed, for 10 patients with localized prostate cancer, to show the reduction of planning target volume (PTV): PTV 10 mm (no markers), PTV 7 mm (markers), and PTV 7/5 mm (markers and online correction). On planning computed tomography (CT) scan, the prostate, bladder, rectal wall, and anal canal were contoured. The treatment volume and radiation doses to surrounding organs were calculated. In 65 patients, with the online protocol and gold markers, late toxicity was evaluated. Results : With gold markers a significant PTV reduction of 27% was achieved (P < .001). Subsequently, radiation dose reductions to the mean of 17% (+/- 4.5%) to the bladder, 19% (+/- 4.7%) to the anal canal, and 12% (+/- 3%) to the rectal wall, respectively were seen (P < .001). With 5-mm posterior margins an additional PTV reduction of 3.7% (P < .001) and total radiation dose reduction to the mean of 24% (+/- 4%), and 16% (+/- 4.5%) to anal canal and rectal wall, respectively were seen (P < .001). Late Grade 1-2 genitourinary and gastrointestinal toxicity was seen in 32%, and 33%, respectively. Grade 3 toxicity was less than 10%. CONCLUSIONS: This study showed a significant reduction of treatment volume and radiation doses to healthy tissues with intraprostatic gold markers

Phase 2 Study of Lutetium 177-Labeled Anti-Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients with Advanced Renal Cell Carcinoma

Despite advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC), there is still an unmet need in the treatment of this disease. A phase 2 radioimmunotherapy (RIT) trial with lutetium 177 ((177)Lu)-girentuximab was initiated to evaluate the efficacy of this approach. In this nonrandomized single-arm trial, patients with progressive metastatic ccRCC who met the inclusion criteria received 2405 MBq/m(2) of (177)Lu-girentuximab intravenously. In the absence of persistent toxicity and progressive disease, patients were eligible for retreatment after 3 mo with 75% of the previous activity dose. A total of 14 patients were included. After the first therapeutic infusion, eight patients (57%) had stable disease (SD) and one (7%) had a partial regression. The treatment was generally well tolerated but resulted in grade 3-4 myelotoxicity in most patients. After the second cycle, continued SD was observed in five of six patients, but none were eligible for retreatment due to prolonged thrombocytopenia. In conclusion, RIT with (177)Lu-girentuximab resulted in disease stabilization in 9 of 14 patients with progressive metastatic ccRCC, but myelotoxicity prevented retreatment in some patients. PATIENT SUMMARY: We investigated the efficacy of lutetium 177-girentuximab radioimmunotherapy in patients with metastatic kidney cancer. The treatment resulted in disease stabilization in 9 of 14 patients. The main toxicity was prolonged low blood cell counts. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02002312 (https://clinicaltrials.gov/ct2/show/NCT02002312)

Chronic pain following laparoscopic living-donor nephrectomy: Prevalence and impact on quality of life

Chronic postsurgical pain (CPSP) following laparoscopic donor nephrectomy (LDN) is a disregarded topic. In this cross-sectional study, all consecutive patients who underwent an LDN at the Radboud University Medical Center (Radboudumc; 2003-2016) were approached for participation. Five hundred twelve living kidney donors were included and asked to complete two questionnaires, including the McGill Pain Questionnaire and the RAND Short Form-36 Health Status Inventory (RAND SF-36) regarding their health-related quality of life (HRQoL). The mean prevalence of CPSP following LDN was 5.7%, with a mean follow-up time of 6 years. Possible predictors of CPSP following LDN are severe early postoperative pain, previous abdominal surgery, and preexisting backache. The RAND SF-36 revealed an impaired HRQoL in patients with CPSP when compared to patients without CPSP. In conclusion, this study revealed that the prevalence of CPSP following LDN is substantial. Given the possible association between the presence of CPSP and impaired HRQoL scores, living kidney donors should be well informed in the preoperative phase about the risk of CPSP

Chronic postsurgical pain after minimally invasive adrenalectomy: prevalence and impact on quality of life

BACKGROUND: Minimally invasive adrenalectomy is the standard of care for small adrenal tumours. Both the transperitoneal lateral approach and posterior retroperitoneal approach are widely used and have been proven to be safe and effective. However, the prevalence of chronic postsurgical pain has not been specifically investigated in previous studies. The primary goal of this study was to identify the prevalence of chronic postsurgical pain after minimally invasive adrenalectomy. METHODS: A cross-sectional study was performed among all consecutive patients who had undergone minimally invasive adrenalectomy in a single university medical centre. The primary outcome was the prevalence of chronic postsurgical pain. Secondary outcomes were the prevalence of localized hypoesthesia, risk factors for the development of chronic postsurgical pain, and the Health-Related Quality of Life. Three questionnaires were used to measure the prevalence and severity of chronic postsurgical pain, hypoesthesia, and Health-Related Quality of Life. Logistic regression analysis was performed to determine risk factors for development of chronic postsurgical pain. RESULTS: Six hundred two patients underwent minimally invasive adrenalectomy between January 2007 and September 2019, of whom 328 signed informed consent. The prevalence of chronic postsurgical pain was 14.9%. In the group of patients with chronic postsurgical pain, 33% reported hypoesthesia as well. Young age was a significant predictor for developing chronic postsurgical pain. The prevalence of localized hypoesthesia was 15.2%. In patients with chronic postsurgical pain, Health-Related Quality of Life was significantly lower, compared to patients without pain. CONCLUSIONS: The prevalence of chronic postsurgical pain following minimally invasive adrenalectomy is considerable. Furthermore, the presence of chronic postsurgical pain was correlated with a significant and clinically relevant lower Health-Related Quality of Life. These findings should be included in the preoperative counselling of the patient. In the absence of evidence for effective treatment in established chronic pain, prevention should be the key strategy and topic of future research

Correlation Between In Vivo F-18-FDG PET and Immunohistochemical Markers of Glucose Uptake and Metabolism in Pheochromocytoma and Paraganglioma

Pheochromocytomas and paragangliomas (PPGLs) can be localized by F-18-FDG PET. The uptake is particularly high in tumors with an underlying succinate dehydrogenase (SDH) mutation. SDHx-related PPGLs are characterized by compromised oxidative phosphorylation and a pseudohypoxic response, which mediates an increase in aerobic glycolysis, also known as the Warburg effect. The aim of this study was to explore the hypothesis that increased uptake of F-18-FDG in SDHx-related PPGLs is reflective of increased glycolytic activity and is correlated with expression of different proteins involved in glucose uptake and metabolism through the glycolytic pathway. Methods: Twenty-seven PPGLs collected from patients with hereditary mutations in SDHB (n = 2), SDHD (n = 3), RET(n = 5), neurofibromatosis 1 (n = 1), and myc-associated factor X (n = 1) and sporadic patients (n = 15) were investigated. Preoperative F-18-FDG PET/CT studies were analyzed; mean and maximum standardized uptake values (SUVs) in manually drawn regions of interest were calculated. The expression of proteins involved in glucose uptake (glucose transporters types 1 and 3 [GLUT-1 and -3, respectively]), phosphorylation (hexokinases 1, 2, and 3 [HK-1, -2, and -3, respectively]), glycolysis (monocarboxylate transporter type 4 [MCT-4]), and angiogenesis (vascular endothelial growth factor [VEGF], CD34) were examined in paraffin-embedded tumor tissues using immunohistochemical staining with peroxidase-catalyzed polymerization of diaminobenzidine as a read-out. The expression was correlated with corresponding SUVs. Results: Both maximum and mean SUVs for SDHx-related tumors were significantly higher than those for sporadic and other hereditary tumors (P &lt;0.01). The expression of HK-2 and HK-3 was significantly higher in SDHx-related PPGLs than in sporadic PPGLs (P = 0.022 and 0.025, respectively). The expression of HK-2 and VEGF was significantly higher in SDHx-related PPGLs than in other hereditary PPGLs (P = 0.039 and 0.008, respectively). No statistical differences in the expression were observed for GLUT-1, GLUT-3, and MCT-4. The percentage anti-CD 34 staining and mean vessel perimeter were significantly higher in SDHx-related PPGLs than in sporadic tumors (P = 0.050 and 0.010, respectively). Mean SUVs significantly correlated with the expression of HK-2 (P = 0.027), HK-3 (P = 0.013), VEGF (P = 9.049), and MCT-4 (P = 0.020). Conclusion: The activation of aerobic glycolysis in SDHx-related PPGLs is associated with increased F-18-FDG accumulation due to accelerated glucose phosphorylation by hexokinases rather than increased expression of glucose transporters