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The aim of this study was to evaluate the measurement properties of the Short Musculoskeletal Function Assessment (SMFA) and Lower Extremity Functional Scale (LEFS) in patients who sustained a tibial shaft fracture, by comparing them with the scores of a general health-related quality of life instrument scale (i.e., EuroQoL-5D). Data of 136 patients participating in a multicenter randomized controlled trial comparing incisions for intramedullary nail entry in adults with a tibial shaft fracture were used. Patients completed the SMFA, LEFS, EQ-5D and an anchor question at 2 and 6 weeks, and at 3, 6 and 12 months. Reliability (internal consistency), construct validity, responsiveness (longitudinal validity), floor and ceiling effects, minimal important change (MIC), and smallest detectable change (SDC) were determined. The SMFA and LEFS (sub)scales showed adequate internal consistency (0.84<α<0.94). Construct and longitudinal validity were also adequate (correctly predicted hypotheses between 83%-100%). Floor effects were not present. Ceiling effects were present at 12 months for the SMFA lower extremity dysfunction and bother subscales (22% and 19%, respectively) and the LEFS (19%). MICs could not be determined with the available data. The SDC was 13.84 points for the SMFA and 38.74 points for the LEFS. This study confirms that the SMFA and LEFS are reliable, valid, and responsive instruments for monitoring functional limitation in patients after sustaining a tibia shaft fracture during at least the first six months post-injury. An anchor-based MIC for the SMFA remains to be determined. [ABSTRACT FROM AUTHOR]

[Display omitted] • >30 % removal for 12 OMPs in both photobioreactors, while < 10 % removal for other 4. • 2 to 3 times higher removal capacity of 9 OMPs in mixed algae-bacterial community. • Predominance of filamentous green algae decreased the removal capacity of 9 OMPs. • Microbial community composition and abundance are important for OMPs removal. Single microalgae species are effective at the removal of various organic micropollutants (OMPs), however increased species diversity might enhance this removal. Sixteen OMPs were added to 2 continuous photobioreactors, one inoculated with Chlorella sorokiniana and the other with a microalgal-bacterial community, for 112 d under natural light. Three media were sequentially used in 3 Periods: I) synthetic sewage (d 0–28), II) 10x diluted anaerobically digested black water (AnBW) (d 28–94) and III) 5x diluted AnBW (d 94–112). Twelve OMPs were removed > 30 %, while 4 were < 10 % removed. Removal efficiencies were similar for 9 OMPs, yet the mixed community showed a 2–3 times higher removal capacity (µg OMP/g dry weight) than C. sorokiniana during Period II pseudo steady state. The removal decreased drastically in Period III due to overgrowth of filamentous green algae. This study shows for the first time how microbial community composition and abundance are key for OMPs removal. [ABSTRACT FROM AUTHOR]

Vocalizations have long been recognized to encode information about an individual's emotional state and, as such, have contributed to the study of emotions in animals. However, the potential of vocalizations to also encode information about an individual's emotional reactivity has received much less attention. In this study, we aimed to test whether the vocalizations of domestic pigs contain correlates of emotional reactivity that are consistent between different contexts. We recorded vocalizations of 120 young female pigs in an experimental arena in two consecutive recording contexts, social isolation and an encounter with a familiar human. Simultaneously, we measured their heart rate and behaviour to determine their emotional reactivity in the same context (within-context). In addition, we aimed to determine the subjects' emotional reactivity in other contexts (across-context) by measuring their behaviour in four common tests of emotional reactivity, the human approach test, the open door test, the open field test and the novel object test. Using a cluster analysis, we identified four different call types. Significant inter-context correlations were found for all call types, suggesting that pig vocalizations are consistent within an individual across contexts. The call rate and the proportions of the individual call types were found to correlate significantly with indices of emotional reactivity both within and across contexts. Thereby, we found more significant correlations to indices of emotional reactivity within context (behavioural and physiological response during recording) compared to across context (behavioural response in the four emotional reactivity tests). The consistency of the vocal correlates to emotional reactivity between the different contexts depended on the call type. While we found moderate evidence that the high grunt is indicative of more active, more explorative and less fearful individuals both within as well as across contexts, the other call types provided less consistent results. Thus, it seems that some call types are better suited to provide information on a caller's emotional reactivity than others, and further research is needed to clarify the underlying influential factors. [ABSTRACT FROM AUTHOR]

The number of elderly patients with renal cell carcinoma is rising. Elderly patients differ from their younger counterparts in, among others, higher incidence of comorbidity and reduced organ function. Age influences outcome of surgery, and therefore has to be taken into account in elderly patients eligible for cytoreductive nephrectomy. Over the last decade several novel effective drugs have become available for the metastatic setting targeting angiogenesis and mammalian target of rapamycin. Immune checkpoint blockade with a programmed death 1 antibody has recently been shown to increase survival and further studies with immune checkpoint inhibitors are ongoing. In this review we summarize the available data on efficacy and toxicity of existing and emerging therapies for metastatic renal cell carcinoma in the elderly. Where possible, we provide evidence-based recommendations for treatment choices in elderly. [ABSTRACT FROM AUTHOR]

In the study of animal emotions, emotional valence has been found to be difficult to measure. Many studies of farm animals' emotions have therefore focussed on the identification of indicators of strong, mainly negative, emotions. However, subtle variations in emotional valence, such as those caused by rather moderate differences in husbandry conditions, may also affect animals' mood and welfare when such variations occur consistently. In this study, we investigated whether repeated moderate aversive or rewarding events could lead to measurable differences in emotional valence in young, weaned pigs. We conditioned 105 female pigs in a test arena to either a repeated startling procedure (sudden noises or appearances of objects) or a repeated rewarding procedure (applesauce, toy and straw) over 11 sessions. Control pigs were also regularly exposed to the same test arena but without conditioning. Before and after conditioning, we measured heart rate and its variability as well as the behavioural reactions of the subjects in the test arena, with a special focus on detailed acoustic analyses of their vocalisations. The behavioural and heart rate measures were analysed as changes compared to the baseline values before conditioning. A limited number of the putative indicators of emotional valence were affected by the conditioning. We found that the negatively conditioned pigs showed changes that were significantly different from those in control pigs, namely a decrease in locomotion and an increase in standing. The positively conditioned pigs, however, showed a stronger increase in heart rate and a smaller decrease in SDNN (a heart rate variability parameter indicating changes in autonomic regulation) compared to the controls. Compared to the negatively conditioned pigs, the positively conditioned pigs produced fewer vocalisations overall as well as fewer low-frequency grunts but more high-frequency grunts. The low-frequency grunts of the negatively conditioned pigs also showed lower frequency parameters (bandwidth, maximum frequency, 25% and 50% quartiles) compared to those of the positively conditioned pigs. In any of the statistically significant results, the conditioning accounted for 1.5–11.9% of variability in the outcome variable. Hence, we conclude that repeated moderate aversive and rewarding events have weak but measurable effects on some aspects of behaviour and physiology in young pigs, possibly indicating changes in emotional valence, which could ultimately affect their welfare. The combination of ethophysiological indicators, i.e., the concurrent examination of heart rate measures, behavioural responses and especially vocalisation patterns, as used in the current study, might be a useful way of examining subtle effects on emotional valence in further studies. [ABSTRACT FROM AUTHOR]

Abstract: In this article we give a systematic review of the nature and design of earlier research into the impact of instructional development in higher education. Studies are clustered on the basis of the level of outcome that was measured, meaning that another synthesis technique is used than in prior reviews related to the same topic. In addition, we address some questions related to the differential impact of initiatives with varied duration, format, or target group, because these questions were left unanswered in earlier reviews. The results of our review provide a guide to improve studies of instructional development in order to get more insight into the real impact at different levels (teachers’ learning, teachers’ behavior, the institution, and the students). Some evidence is found of the influence of the duration and nature of instructional development on its impact. [Copyright &y& Elsevier]

Insertion of additional octarepeats into the prion protein gene has been genetically linked to familial Creutzfeldt Jakob disease and hence to de novo generation of infectious prions. The pivotal event during priori formation is the conversion of the normal prion protein (PrPC) into the pathogenic conformer PrPSc, which subsequently induces further conversion in an autocatalytic manner. Apparently, an expanded octarepeat domain directs folding of PrP toward the PrPSc conformation and initiates a self-replicating conversion process. Here, based on three main observations, we have provided a model on how altered molecular interactions between wild-type and mutant PrP set the stage for familial Creutzfeldt Jakob disease with octarepeat insertions. First, we showed that wild-type octarepeat domains interact in a copper-dependent and reversible manner, a ‘copper switch.’ This interaction becomes irreversible upon domain expansion, possibly reflecting a loss of function. Second, expanded octarepeat domains of increasing length gradually form homogenous globular multimers of 11–21 nm in the absence of copper ions when expressed as soluble glutathione S-transferase fusion proteins. Third, octarepeat domain expansion causes a gain of function with at least 10 repeats selectively binding PrPSc in a denaturant-resistant complex in the absence of copper ions. Thus, the combination of both a loss and gain of function profoundly influences homomeric interaction behavior of PrP with an expanded octarepeat domain. A multimeric cluster of prion proteins carrying expanded octarepeat domains may therefore capture and incorporate spontaneously arising short-lived PrpSc-like conformers, thereby providing a matrix for their conversion. [ABSTRACT FROM AUTHOR]

Cites the inducement of tumor-specific apoptosis as a globular multimer through apoptin. Formation of noncovalent globular aggregates by recombinant apoptin proteins; Irreversibility of the multimerization; Mapping of the structural motifs responsible for multimerization in vitro.

Investigates how a possible restrictive South African migrant labor policy may affect the survival of households in Swaziland. Information on survey data used in the study; History of foreign labor migration to South Africa; Statistics on income generation.

Chronic kidney disease is a major health concern, and experimental models bridging the gap between animal studies and clinical research are currently lacking. Here, we evaluated precision-cut kidney slices (PCKSs) as a potential model for renal disease. PCKSs were prepared from human cortical tissue obtained from tumor nephrectomies and cultured up to 96 hours. Morphology, cell viability, and metabolic functionality (ie, uridine 5'-diphospho-glucuronosyltransferase and transporter activity) were determined to assess the integrity of PCKSs. Furthermore, inflammatory and fibrosis-related gene expressions were characterized. Finally, to validate the model, renal fibrogenesis was induced using transforming growth factor β1 (TGF-β1). Preparation of PCKSs induced an inflammatory tissue response, whereas long-term incubation (96 hours) induced fibrogenesis as shown by an increased expression of collagen type 1A1 (COL1A1) and fibronectin 1 (FN1). Importantly, PCKSs remained functional for more than 48 hours as evidenced by active glucuronidation and phenolsulfonphthalein uptake. In addition, cellular diversity appeared to be maintained, yet we observed a clear loss of nephrin messenger RNA levels suggesting that our model might not be suitable to study the role of podocytes in renal pathology. Moreover, TGF-β1 exposure augmented fibrosis, as illustrated by an increased expression of multiple fibrosis markers including COL1A1, FN1, and α-smooth muscle actin. In conclusion, PCKSs maintain their renal phenotype during culture and appear to be a promising model to investigate renal diseases, for example, renal fibrosis. Moreover, the human origin of PCKSs makes this model very suitable for translational research. [ABSTRACT FROM AUTHOR]

Although level I evidence is lacking that radical cystectomy (RC) is superior to bladder-preserving therapy (BPT), RC is still advocated as the recommended treatment in patients with nonmetastatic muscle-invasive bladder cancer (MIBC). This study sought to compare the survival of patients with MIBC treated with BPT versus those treated with RC. All patients with nonmetastatic MIBC diagnoses were identified via the population-based Netherlands Cancer Registry. Only patients treated with BPT or RC were included. The primary endpoint was 2-year disease-free survival (DFS), defined as time from start of treatment until locoregional recurrence, distant metastasis, or death. The secondary endpoint was overall survival (OS). Inverse propensity treatment weighting (IPTW) was used based on propensity scores to adjust for baseline differences between treatment groups. Survival was analyzed with Kaplan-Meier and Cox proportional hazards models. A total of 1432 patients were included, of whom 1101 underwent RC and 331, BPT. Median follow-up was 39 months (range, 27-51 months). The IPTW-adjusted 2-year DFS was 61.5% (95% CI, 53.5%-69.6%) with BPT and 55.3% (95% CI, 51.6%-59.1%) with RC, with an adjusted hazard ratio of 0.84 (95% CI, 0.69-1.05). The adjusted 2-year OS for patients treated with BPT versus RC was 74.0% (95% CI, 67.0%-80.9%) versus 66.0% (95% CI, 62.7%-68.8%), respectively, with an adjusted hazard ratio of 0.80 (95% CI, 0.64-0.98). There was no statistically significant difference between the 2-year DFS of patients treated with BPT and RC. We propose that both RC and BPT should be offered as a curative treatment option to eligible patients with nonmetastatic MIBC. [ABSTRACT FROM AUTHOR]

Purpose: An elevated serum prostate-specific antigen (PSA) level cannot distinguish between local-regional recurrences and the presence of distant metastases after treatment with curative intent for prostate cancer. With the advent of salvage treatment such as cryotherapy, it has become important to localize the site of recurrence (local or distant). In this study, the potential of (11)C-choline positron emission tomography (PET) to identify site of recurrence was investigated in patients with rising PSA after external-beam radiotherapy (EBRT). Methods and Materials: Seventy patients with histologically proven prostate cancer treated with EBRT and showing biochemical recurrence as defined by American Society for Therapeutic Radiology and Oncology consensus statement and 10 patients without recurrence underwent a PET scan using 400 MBq (11)C-choline intravenously. Biopsy-proven histology from the site of suspicion, findings with other imaging modalities, clinical follow-up and/or response to adjuvant therapy were used as comparative references. Results: None of the 10 patients without biochemical recurrence had a positive PET scan. Fifty-seven of 70 patients with biochemical recurrence (median PSA 9.1 ng/mL; mean PSA 12.3 ng/mL) showed an abnormal uptake pattern (sensitivity 81%). The site of recurrence was only local in 41 of 57 patients (mean PSA 11.1 ng/mL at scan), locoregionally and/or distant in 16 of 57 patients (mean PSA 17.7 ng/mL). Overall the positive predictive value and negative predictive value for (11)C-choline PET scan were 1.0 and 0.44 respectively. Accuracy was 84%. Conclusions: (11)C-choline PET scan is a sensitive technique to identify the site of recurrence in patients with PSA relapse after EBRT for prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract: The prion protein, PrP, exists in several stable conformations, with the presence of one conformation, PrPSc, associated with transmissible neurodegenerative diseases. Targeting PrP by high-affinity ligands has been proven to be an effective way of preventing peripheral prion infections. Here, we have generated bacterially expressed single chain fragments of the variable domains (scFv) of a monoclonal antibody in Escherichia coli, originally raised against purified PrPSc that recognizes both PrPC and PrPSc. This scFv fragment had a dissociation constant (K D) with recombinant PrP of 2nM and cleared prions in ScN2a cells at 4nM, as demonstrated by a mouse prion bioassay. A peptide corresponding to the complementarity determining region 3 of the heavy chain (CDR3H) selectively bound PrPSc but had lost antiprion activity. However, synthesis and application of an improved peptide mimicking side chain topology of CDR3H while exhibiting increased protease resistance, a retro-inverso d-peptide of CDR3H, still bound PrPSc and reinstated antiprion activity. We conclude that (1) scFvW226 is so far the smallest polypeptide with bioassay confirmed antiprion activity, and (2) differential conformation specificity and bioactivity can be regulated by orchestrating the participation of different CDRs. [Copyright &y& Elsevier]

The chicken anemia virus-derived protein Apoptin induces apoptosis specifically in human tumor and transformed cells and not in normal, untransformed cells. The cell killing activity correlates with a predominantly nuclear localization of Apoptin in tumor cells, whereas in normal cells, it is detected mainly in cytoplasmic structures. To explore the role of nuclear localization for Apoptin-induced cell death in tumor cells, we employed a mutagenesis strategy. First, we demonstrated that the C terminus of Apoptin contains a bipartite-type nuclear localization signal. Strikingly, further investigation showed that Apoptin contains two different domains that induce apoptosis independently, and for both domains, we found a strong correlation between localization and killing activity. Using inhibitors, we ruled out the involvement of de novo gene transcription and translation and further showed that Apoptin itself does not have any significant transcriptional repression activity, suggesting that Apoptin exerts its effects in the nucleus by some other method. To determine whether nuclear localization is sufficient to enable Apoptin to kill normal, untransformed cells, we expressed fulllength Apoptin fused to a heterologous nuclear localization signal in these cells. However, despite its nuclear localization, no apoptosis was induced, which suggests that nuclear localization per se is not sufficient for Apoptin to become active. These studies increase our understanding of the molecular pathway of Apoptin and may also shed light on the mechanism of cellular transformation. [ABSTRACT FROM AUTHOR]

In patients with prostate cancer who have a high risk of pelvic nodal disease, the use of elective whole pelvis radiotherapy is still controversial. Two large, randomised, controlled trials (RTOG 9413 and GETUG-01) did not show a benefit of elective whole pelvis radiotherapy over prostate-only radiotherapy. In 2020, the POP-RT trial established the role of elective whole pelvis radiotherapy in patients who have more than a 35% risk of lymph node invasion (known as the Roach formula). POP-RT stressed the importance of patient selection. In patients with cN1 (clinically node positive) disease or pN1 (pathologically node positive) disease, the addition of whole pelvis radiotherapy to androgen deprivation therapy significantly improved survival compared with androgen deprivation therapy alone, as shown in large, retrospective studies. This patient population might increase in the future because use of the more sensitive prostate-specific membrane antigen PET-CT will become the standard staging procedure. Additionally, the SPORTT trial suggested a benefit of whole pelvis radiotherapy in biochemical recurrence-free survival in the salvage setting. A correct definition of the upper field border, which should include the bifurcation of the abdominal aorta, is key in the use of pelvic radiotherapy. As a result of using modern radiotherapy technology, severe late urinary and intestinal toxic effects are rare and do not seem to increase compared with prostate-only radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: In patients with open tibial fractures, bone and wound infections are associated with an increased hospital length of stay and higher costs. The infection risk increases with the use of implants. Innovations to reduce this risk include antibiotic-coated implants. This study models whether the use of a gentamicin-coated intramedullary tibial nail is cost-effective for trauma centers managing patients with a high risk of infection.Efficacy: Absolute infection risk and relative risk reduction, by fracture grade, for antibiotic-coated nails compared to standard nails for patients with open tibial fractures were estimated based on the results of a meta-analysis, which assessed the additional benefit of locally-administered prophylactic antibiotics in open tibia fractures treated with implants. The observed efficacy of antibiotic-coated nails in reducing infections was applied in an economic model.Methods: The model compared infection rates, inpatient days, theatre usage and costs in high risk patients, with a Gustilo-Anderson (GA) grade III open fracture, for two patient cohorts from a trauma center perspective, with a 1-year time horizon. In one cohort all GAIII patients received a gentamicin-coated nail whilst GAI and GAII patients received a standard nail. All patients in the comparator cohort received a standard nail. Four European trauma centers provided patient-level data (n=193) on inpatient days, procedures and related costs for patients with and without infections.Results: Using the gentamicin-coated nail in patients at high risk of infection (GAIII) was associated with 75% lower rate of infection and cost savings (€477 - €3.263) for all included centers; the higher cost of the implant was offset by savings from fewer infections, inpatient days (-26%) and re-operations (-10%). This result was confirmed by extensive sensitivity analyses.Conclusions: Analyses demonstrated that infection rates and total costs for in-hospital treatment could be potentially reduced by 75% and up to 15% respectively, by using a gentamicin-coated nail in patients at high risk of infection. Fewer infections, reduced inpatient days and re-operations may be potentially associated with use of antibiotic-coated implants. Results are sensitive to the underlying infection risk, with greatest efficacy and cost-savings when the coated implant is used in high risk patients. [ABSTRACT FROM AUTHOR]

Organ-sparing treatment has become the standard of curative cancer treatment for many tumor types. For patients with muscle invasive bladder cancer (MIBC), radical cystectomy (RC) is still the recommended treatment according to both the American Urological Association and the European Association of Urology guidelines. An attempted RCT between RC and bladder sparing therapy (BST) failed due to low accrual and noncompliance. A large prospective comparative study is the best alternative to compare outcomes between modalities. We hypothesized that the two-year disease-free survival (DFS) with BST is equal to the DFS with RC in selected patients with non-metastasized MIBC. All patients diagnosed with MIBC between November 2017 and November 2019 were identified via the population-based Netherlands Cancer Registry. Detailed clinical data was retrieved by consulting medical files. Only patients treated with BST or RC were included. BST was defined as patients treated with concurrent chemoradiation (CRT) or external beam radiation followed by brachytherapy (BT). The primary endpoint was DFS, defined as free from muscle invasive locoregional recurrence, distant metastasis or death. Secondary endpoint was overall survival (OS). Two-year follow-up (FU) data were collected Survival was analyzed with a Cox proportional hazards model, we present the crude results in this abstract. Time was defined from treatment start to first event. Patients were censored at end of FU if alive or at last contact if lost to follow-up. A total of 1429 patients were included, 1100 underwent RC, 283 concurrent CRT and 44 BT. Median follow-up was 22 months (range: 1-43 months). Patients treated by RC and BST had similar DFS with a crude HR 0.96 (95%CI 0.78-1.16). The 2-year DFS for patients treated by RC, concurrent CRT or BT was 56% (95%CI 53-60%), 56% (95%CI 50-63%) and 67% (95%CI 52-82%) respectively. After a median time of 15.8 months, salvage cystectomy was performed in 21 patients (6,4%) of which 17 in the CRT and 4 in the BT group. The 2-year OS for patients treated with RC, concurrent CRT or BT was 63.8% (95%CI 61-67%), 68.3% (95%CI 62-74%) and 85.9% (95%CI 75-96%) respectively. The crude HR for OS was 0.84, 95%CI 0.66-1.05, (p=0.14) for RC vs CRT and 0.40 95%CI 0.17-0.77(p=0.015) for RC vs BT. Our study is limited by the inherent biases of observational data. At two years, DFS did not significantly differ between patients treated with BST and RC. We conclude that after appropriate selection BST leads to similar DFS rates compared to RC. Nevertheless, these results should be interpreted with care, as the treatment groups were not yet matched for case-mix variables. The results of this study can be used to aid patients and physicians to choose the modality best tailored to their individual preferences. [ABSTRACT FROM AUTHOR]

Background: Both disrupted-in-schizophrenia 1 (DISC1) and dysbindin have been identified as schizophrenia candidate genes in independent genetic linkage studies. The proteins have been assigned distinct subcellular locations and functions. We investigated whether both proteins converge into a common pathway specific for schizophrenia or mental diseases. Methods: DISC1 and dysbindin were expressed as recombinant proteins with or without a fluorescent protein-tag in human or mouse neuroblastoma cells and as recombinant proteins in E. coli. Postmortem brains of patients with mental diseases from the Stanley Research Medical Institute''s Consortium Collection were used to demonstrate molecular interactions in biochemically purified protein fractions. Results: First, upon overexpression in neuroblastoma cells, DISC1 formed aggresomes that recruited homologous soluble C-terminal DISC1 fragment or heterologous dysbindin. Domains involved in binding could be mapped to DISC1 (316-597) and dysbindin (82-173), indicating a specific interaction. In addition, recruitment was demonstrated when externally added, purified DISC1 aggresomes penetrated recipient cells after coincubation. Second, a direct interaction between soluble DISC1 protein and dysbindin was demonstrated in a cell free system using E. coli-expressed proteins. Third, co-aggregation of DISC1 and dysbindin was demonstrated in postmortem brains for a subgroup of cases with chronic mental disease but not healthy control subjects. Conclusions: A direct interaction of soluble and insoluble DISC1 protein with dysbindin protein demonstrates convergence of so far considered independent mental disease genes by direct molecular interaction. Our findings highlight protein aggregation and recruitment as a biological mechanism in mental disease. [Copyright &y& Elsevier]

Summary: Hereditary nonpolyposis colorectal cancer, or Lynch syndrome, is responsible for 2–3% of all colorectal cancers. Lynch syndrome is also associated with a high risk of extracolonic cancers, including endometrial, stomach, small bowel, pancreas, biliary tract, ovary, urinary tract, brain, and skin cancer. In this Review, we discuss the risks, surveillance tests, and guidelines for the management of extracolonic tumours associated with Lynch syndrome. For all types of extracolonic cancer, evidence supporting surveillance is scarce. A benefit of surveillance is evident only for endometrial cancer, where transvaginal ultrasound and endometrial sampling detect tumours in early stages. Surveillance is generally recommended for urinary tract and gastric cancer, especially in families with more than one member with these types of cancer. For the other types of cancer, surveillance is typically not recommended. Prophylactic hysterectomy and bilateral salpingo-oophorectomy should be considered for women with Lynch syndrome who are past childbearing age, especially during surgery for colorectal cancer. No data show efficacy of chemopreventive drugs in reducing the risk of extracolonic cancers for patients with Lynch syndrome. [Copyright &y& Elsevier]