More than a decade after live donor nephrectomy: a prospective cohort study

Item does not contain fulltextPreviously reported short-term results after live kidney donation show no negative consequences for the donor. The incidence of new-onset morbidity takes years to emerge, making it highly likely that this will be missed during short-term follow-up. Therefore, evidence on long-term outcome is essential. A 10-year follow-up on renal function, hypertension, quality of life (QOL), fatigue, and survival was performed of a prospective cohort of 100 donors. After a median follow-up time of 10 years, clinical data were available for 97 donors and QOL data for 74 donors. Nine donors died during follow-up of unrelated causes to donation, and one donor was lost to follow-up. There was a significant decrease in kidney function of 12.9 ml/min (P < 0.001) at follow-up. QOL showed significant clinically relevant decreases of 10-year follow-up scores in SF-36 dimensions of physical function (P < 0.001), bodily pain (P = 0.001), and general health (P < 0.001). MFI-20 scores were significantly higher for general fatigue (P < 0.001), physical fatigue (P < 0.001), reduced activity (P = 0.019), and reduced motivation (P = 0.030). New-onset hypertension was present in 25.6% of the donors. Donor outcomes are excellent 10 years post-donation. Kidney function appears stable, and hypertension does not seem to occur more frequently compared to the general population

Cost-effectiveness of hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy: a randomized study

Item does not contain fulltextBACKGROUND: Live kidney donation has a clear economical benefit over dialysis and deceased-donor transplantation. Compared with mini-incision open donor nephrectomy, laparoscopic donor nephrectomy (LDN) is considered cost-effective. However, little is known on the cost-effectiveness of hand-assisted retroperitoneoscopic donor nephrectomy (HARP). This study evaluated the cost-effectiveness of HARP versus LDN. METHODS: Alongside a randomized controlled trial, the cost-effectiveness of HARP versus LDN was assessed. Eighty-six donors were included in the LDN group and 82 in the HARP group. All in-hospital costs were recorded. During follow-up, return-to-work and other societal costs were documented up to 1 year. The EuroQol-5D questionnaire was administered up to 1 year postoperatively to calculate quality-adjusted life years (QALYs). RESULTS: Mean total costs from a healthcare perspective were $8935 for HARP and$8650 for LDN (P=0.25). Mean total costs from a societal perspective were $16,357 for HARP and$16,286 for LDN (P=0.79). On average, donors completely resumed their daytime jobs on day 54 in the HARP group and on day 52 in the LDN group (P=0.65). LDN resulted in a gain of 0.005 QALYs. CONCLUSIONS: Absolute costs of both procedures are very low and the differences in costs and QALYs between LDN and HARP are very small. Other arguments, such as donor safety and pain, should determine the choice between HARP and LDN

Multivariate Analysis of Health-related Quality of Life in Donors After Live Kidney Donation

Item does not contain fulltextBACKGROUND: Live-kidney donation has a low mortality rate. Evidence suggests that live-kidney donors experience a quality of life (QoL) comparable to or even superior to that of the general population. There is limited information on factors associated with a decrease in QoL in particular for baseline factors, which would improve information to the donor, donor selection, and convalescence. METHODS: QoL data on 501 live donors included in three prospective studies between 2001 and 2010 were used. The 36-item short form health survey (SF-36) was used to measure QoL up to 1 year after the procedure. Longitudinal effects on both the mental (MCS) and physical component scales (PCS) were analyzed with multilevel linear regression analyses. Baseline variables were age, gender, body mass index (BMI), pain, operation type, and comorbidity. Other covariates were loss of the graft, glomerular filtration rate, and recipient complications. RESULTS: After 1 year we observed a small decrease in PCS (effect size = -0.24), whereas the MCS increased (effect size = 0.32). Both PCS and MCS were still well above the norm of the general Dutch population. Factors associated with a change in PCS were BMI (Cohen's d = -0.17 for 5 BMI points) and age (d = -0.13 for each 10 years older). CONCLUSIONS: Overall, QoL after live-donor nephrectomy is excellent. A lowered PCS is related to age and body weight. Expectations towards a decreased postoperative QoL at 1 year are unjustified. However, one should keep in mind that older and obese donors may develop a reduced physical QoL after live-kidney donation

Cost effectiveness of laparoscopic versus mini-incision open donor nephrectomy: a randomized study.

BACKGROUND: Cost-effectiveness remains an issue surrounding the introduction of laparoscopic donor nephrectomy (LDN). METHODS: In a randomized controlled trial the cost-effectiveness of LDN versus mini-incision open donor nephrectomy (ODN) was determined. Fifty donors were included in each group. All in-hospital costs were documented. Postoperatively, case record forms were sent to the donors during 1-year follow-up to record return-to-work and societal costs. To offset costs against quality of life, the Euroqol-5D questionnaire was administered preoperatively and 3, 7, 14, 28, 90, 180, and 365 days postoperatively. RESULTS: Mean total costs were euro6,090 (US$7,308) after LDN and euro4,818 ($5,782) after ODN (P<0.001). Disposables influenced the cost difference most. Mean productivity loss was 68 and 75 days after LDN and ODN respectively, corresponding to euro783 ($940) gained per donor after LDN. The main gain in quality of life in the LDN group was realized within 4 weeks postoperatively. LDN resulted in a mean gain of 0.03 quality-adjusted life years at mean costs of euro1,271 ($1,525) and euro488 ($586) from a healthcare perspective and a societal perspective, respectively. This implies that one additional Quality-Adjusted Life Year after LDN costs about euro16,000 ($19,200) from a societal point of view and about euro41,000 ($49,200) from a health-care perspective. Activities other than work were resumed significantly earlier after LDN (66 vs. 91 days, P=0.01). CONCLUSION: In addition to a clinically relevant donor-experienced benefit from LDN, this technique appeared, given a societal perspective, a cost-efficient procedure mainly due to less productivity losses

Treatment of Isolated Peritoneal Recurrences in Patients with Colorectal Peritoneal Metastases Previously Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Contains fulltext : 192301.pdf (publisher's version ) (Closed access

Comparison of laparoscopic and mini incision open donor nephrectomy: single blind, randomised controlled clinical trial.

Contains fulltext : 51272.pdf (publisher's version ) (Open Access)OBJECTIVES: To determine the best approach for live donor nephrectomy to minimise discomfort to the donor and to provide good graft function. DESIGN: Single blind, randomised controlled trial. SETTING: Two university medical centres, the Netherlands. PARTICIPANTS: 100 living kidney donors. INTERVENTIONS: Participants were randomly assigned to either laparoscopic donor nephrectomy or to mini incision muscle splitting open donor nephrectomy. MAIN OUTCOME MEASURES: The primary outcome was physical fatigue using the multidimensional fatigue inventory 20 (MFI-20). Secondary outcomes were physical function using the SF-36, hospital stay after surgery, pain, operating times, recipient graft function, and graft survival. RESULTS: Conversions did not occur. Compared with mini incision open donor nephrectomy, laparoscopic donor nephrectomy resulted in longer skin to skin time (median 221 v 164 minutes, P < 0.001), longer warm ischaemia time (6 v 3 minutes, P < 0.001), less blood loss (100 v 240 ml, P < 0.001), and a similar number of complications (intraoperatively 12% v 6%, P = 0.49, postoperatively both 6%). After laparoscopic nephrectomy, donors required less morphine (16 v 25 mg, P = 0.005) and shorter hospital stay (3 v 4 days, P = 0.003). During one year's follow-up mean physical fatigue was less (difference - 1.3, 95% confidence interval - 2.4 to - 0.1) and physical function was better (difference 6.2, 2.0 to 10.3) after laparoscopic nephrectomy. Function of the graft and graft survival rate of the recipient at one year censored for death did not differ (100% after laparoscopic nephrectomy and 98% after open nephrectomy). CONCLUSIONS: Laparoscopic donor nephrectomy results in a better quality of life compared with mini incision open donor nephrectomy but equal safety and graft function

Purification and biochemical characterization of recombinant Persicaria minor β-sesquiphellandrene synthase

Background. Sesquiterpenes are 15-carbon terpenes synthesized by sesquiterpene synthases using farnesyl diphosphate (FPP) as a substrate. Recently, a sesquiterpene synthase gene that encodes a 65 kDa protein was isolated from the aromatic plant Persicaria minor. Here, we report the expression, purification and characterization of recombinant P. minor sesquiterpene synthase protein (PmSTS). Insights into the catalytic active site were further provided by structural analysis guided by multiple sequence alignment. Methods. The enzyme was purified in two steps using affinity and size exclusion chromatography. Enzyme assays were performed using the malachite green assay and enzymatic product was identified using gas chromatography-mass spectrometry (GCMS) analysis. Sequence analysis of PmSTS was performed using multiple sequence alignment (MSA) against plant sesquiterpene synthase sequences. The homology model of PmSTS was generated using I-TASSER server. Results. Our findings suggest that the recombinant PmSTS is mainly expressed as inclusion bodies and soluble aggregate in the E. coli protein expression system. However, the addition of 15% (v/v) glycerol to the protein purification buffer and the removal of N-terminal 24 amino acids of PmSTS helped to produce homogenous recombinant protein. Enzyme assay showed that recombinant PmSTS is active and specific to the C15 substrate FPP. The optimal temperature and pH for the recombinant PmSTS are 30 °C and pH 8.0, respectively. The GC-MS analysis further showed that PmSTS produces β-sesquiphellandrene as a major product and β-farnesene as a minor product. MSA analysis revealed that PmSTS adopts a modified conserved metal binding motif (NSE/DTE motif). Structural analysis suggests that PmSTS may binds to its substrate similarly to other plant sesquiterpene synthases. Discussion. The study has revealed that homogenous PmSTS protein can be obtained with the addition of glycerol in the protein buffer. The N-terminal truncation dramatically improved the homogeneity of PmSTS during protein purification, suggesting that the disordered N-terminal region may have caused the formation of soluble aggregate.We further show that the removal of the N-terminus disordered region of PmSTS does not affect the product specificity. The optimal temperature, optimal pH, Km and kcat values of PmSTS suggests that PmSTS shares similar enzyme characteristics with other plant sesquiterpene synthases. The discovery of an altered conserved metal binding motif in PmSTS through MSA analysis shows that the NSE/DTE motif commonly found in terpene synthases is able to accommodate certain level of plasticity to accept variant amino acids. Finally, the homology structure of PmSTS that allows good fitting of substrate analog into the catalytic active site suggests that PmSTS may adopt a sesquiterpene biosynthesis mechanism similar to other plant sesquiterpene synthases

Randomized controlled trial comparing hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy

Contains fulltext : 136652.pdf (publisher's version ) (Closed access)BACKGROUND: Laparoscopic donor nephrectomy (LDN) has become the gold standard for live-donor nephrectomy, as it results in a short convalescence time and increased quality of life. However, intraoperative safety has been debated, as severe complications occur incidentally. Hand-assisted retroperitoneoscopic donor nephrectomy (HARP) is an alternative approach, combining the safety of hand-guided surgery with the benefits of endoscopic techniques and retroperitoneal access. We assessed the best approach to optimize donors' quality of life and safety. METHODS: In two tertiary referral centers, donors undergoing left-sided nephrectomy were randomly assigned to HARP or LDN. Primary endpoint was physical function, one of the dimensions of the Short Form-36 questionnaire on quality of life, at 1 month postoperatively. Secondary endpoints included intraoperative events and operation times. Follow-up was 1 year. RESULTS: In total, 190 donors were randomized. Physical function at 1 month follow-up did not significantly differ between groups (estimated difference, 1.79; 95% confidence interval, -4.1 to 7.68; P=0.55). HARP resulted in significantly shorter skin-to-skin time (mean, 159 vs. 188 min; P<0.001), shorter warm ischemia time (2 vs. 5 min; P<0.001) and a lower intraoperative event rate (5% vs. 11%, P=0.117). Length of stay (both 3 days; P=0.135) and postoperative complication rate (8% vs. 8%; P=1.00) were not significantly different. Potential graft-related complications did not significantly differ (6% vs. 13%; P=0.137). CONCLUSIONS: Compared with LDN, left-sided HARP leads to similar quality of life, shorter operating time, and warm ischemia time. Therefore, we recommend HARP as a valuable alternative to the laparoscopic approach for left-sided donor nephrectomy

The impact of an open or laparoscopic approach on the development of metachronous peritoneal metastases after primary resection of colorectal cancer: results from a population-based cohort study

Background This study aimed to assess the impact of open or laparoscopic resection of primary colorectal cancer (CRC) on the development of metachronous colorectal peritoneal metastases (CPM) in a population-based cohort. Materials and methods This was a retrospective, population-based study of CRC patients who underwent open or laparoscopic resection of the primary tumour in the Netherlands between January 1st and June 30th 2015. Patients with synchronous metastases were excluded. CPM were considered metachronous if diagnosed >= 90 days after resection of primary CRC. Multivariable cox regression analysis was performed to correct for tumour location, histology, differentiation, and stage, nodal stage, tumour perforation, primary surgery type, and unclear resection margins. Results In total, 1516 CRC patients underwent open resection and 3236 CRC patients underwent laparoscopic resection, with a 3-year cumulative incidence of metachronous CPM of 7.3% and 3.7%, respectively (p < 0.001), after median follow-up of 42 months. Open surgical approach was significantly associated with the development of metachronous CPM: HR 1.4 [95%CI 1.1-1.8]. Other prognostic factors were mucinous adenocarcinoma histology (HR 1.6, 95%CI 1.0-2.5), T4 stage (HR 3.2, 95%CI 2.3-4.5), N1 stage (HR 2.9, 95%CI 2.1-4.0), and N2 stage (HR 4.2, 95%CI 2.9-6.1). Conclusions Patients treated with open resection had a significantly higher risk to develop metachronous CPM than patients treated with laparoscopic resection. The mechanisms underlying this phenomenon remain unknown but might be related to differences in per-operative specimen handling, tumour spill, surgical trauma and pro-inflammatory response. This finding might imply the need for a personalized follow-up after primary resection of CRC

Clinical relevance of occult tumor cells in lymph nodes from gastric cancer patients.

Contains fulltext : 48795.pdf (publisher's version ) (Closed access)The current method for staging in gastric cancer is not sufficient as even after a complete primary tumor resection, patients with node-negative gastric cancer suffer from disease recurrence. In this study, the relation between disease recurrence and the presence of occult tumor cells (OTC) in lymph nodes from gastric cancer patients was evaluated. In a case-control design, lymph nodes from 40 cases (disease recurrence) and 41 controls (no disease recurrence and followed for at least five years) with gastric cancer were examined for the presence of OTC, that comprised micrometastases (MM; >0.2 mm and < or =2.0 mm) and isolated tumor cells (ITC; < or =0.2 mm). The original hematoxylin and eosin-stained sections of all lymph nodes from cases and controls were previously considered as tumor-negative by the local pathologist. Fresh hematoxylin and eosin-stained sections were screened by conventional microscopy. Histologic sections stained by immunohistochemistry with anticytokeratin antibodies CAM5.2 were screened by conventional and automated microscopy. Tumor cells were detected in lymph nodes from 40 of 81 (49%) patients. There was no significant difference in the presence of OTC, MM, or ITC between the case and control groups (P = 0.658, P = 0.691, P = 0.887, respectively). However, significantly more cases presented with 20% or more OTC-positive lymph nodes (P = 0.015). A multivariate logistic regression analysis showed that examination of less than five lymph nodes (odds ratio, 13.8; 95% confidence interval, 1.6-120.6, P = 0.018) was the only significant independent risk factor for disease recurrence, especially for locoregional disease recurrence (odds ratio, 20.4; 95% confidence interval, 2.2-190.8, P = 0.008). A similar analysis for distant disease recurrence showed a percentage of 20% or more OTC-positive lymph nodes to be the only significant independent risk factor (odds ratio, 15.6, 95% confidence interval, 1.6-151.4, P = 0.018). The sensitivity of immunohistochemistry evaluated by microscopy to identify cases with 20% or more OTC-positive lymph nodes increased from 8% for conventional microscopy to 22% for automated microscopy (McNemar's test, P = 0.063). The mere presence of OTC-positive lymph nodes in gastric cancer patients did not predict disease recurrence. However, the number of examined lymph nodes and the percentage of OTC-positive lymph nodes were independent risk factors for locoregional disease recurrence and distant disease recurrence, respectively. Automated microscopy was essential in identifying patients with 20% or more OTC-positive lymph nodes. Therefore, a maximum number of lymph nodes should be removed and meticulously examined for OTC to identify high-risk patients. These patients should be considered for additional treatment