Surveillance for low-risk kidney cancer: a narrative review of contemporary worldwide practices.

The management trend of low-risk kidney cancer over the last decade has been from treatment with radical nephrectomy, to use of nephron sparing procedures of partial nephrectomy and ablation, as well as the option of active surveillance (AS). This narrative review aims to summarise the available guidelines related to AS and review the published descriptions of regional practices on the management of low-risk kidney cancer worldwide. A search of PubMed, Google Scholar and Cochrane Library databases for studies published 2010 to June 2020 identified 15 studies, performed between 2000 and 2019, which investigated 13 different cohorts of low-risk kidney cancer patients on AS. Although international guidelines show a level of agreement in their recommendation on how AS is conducted, in terms of patient selection, surveillance strategy and triggers for intervention, cohort studies show distinct differences in worldwide practice of AS. Prospective studies showed general agreement in their predefined selection criteria for entry into AS. Retrospective studies showed that patients who were older, with greater comorbidities, worse performance status and smaller tumours were more likely to be managed with AS. The rate of percutaneous renal mass biopsy varied between studies from 2% to 56%. The surveillance protocol was different across all studies in terms of recommended modality and frequency of imaging. Of the 6 studies which had set indications for intervention, these were broadly in agreement. Despite clear criteria for intervention, patient or surgeon preference was still the reason in 11-71% of cases of delayed intervention across 5 studies. This review shows that AS is being applied in a variety of centres worldwide and that key areas of patient selection criteria and surveillance strategy have large similarities. However, the rate of renal mass biopsy and of delayed intervention varies significantly between studies, suggesting the process of diagnosing malignant SRM and decision making whilst on AS are varying in practice. Further research is needed on the diagnosis and characterisation of incidentally found small renal masses (SRM), using imaging and histology, and the natural history of these SRM in order to develop evidence-based active surveillance protocols.

The utility of automated volume analysis of renal stones before and after shockwave lithotripsy treatment.

This study aimed to evaluate the additional utility of an automated method of estimating volume for stones being treated with shockwave lithotripsy (SWL) using computed tomography (CT) images compared to manual measurement. Utility was assessed as the ability to accurately measure stone burden before and after SWL treatment, and whether stone volume is a better predictor of SWL outcome than stone diameter. 72 patients treated with SWL for a renal stone with available CT scans before and after treatment were included. Stone axes measurement and volume estimation using ellipsoid equations were compared to volume estimation using software using CT textural analysis (CTTA) of stone images. There was strong correlation (r > 0.8) between manual and CTTA estimated stone volume. CTTA measured stone volume showed the highest predictive value (r2 = 0.217) for successful SWL outcome on binary logistic regression analysis. Three cases that were originally classified as 'stone-free with clinically insignificant residual fragments' based on manual axis measurements actually had a larger stone volume based on CTTA estimation than the smallest fragments remaining for cases with an outcome of 'not stone-free'. This study suggests objective measurement of total stone volume could improve estimation of stone burden before and after treatment. Current definitions of stone-free status based on manual measurements of residual fragment sizes are not accurate and may underestimate remaining stone burden after treatment. Future studies reporting on the efficacy of different stone treatments should consider using objective stone volume measurements based on CT image analysis as an outcome measure of stone-free state.

Utility of blood tests in screening for metabolic disorders in kidney stone disease.

OBJECTIVES: To determine the clinical utility of blood tests as a screening tool for metabolic abnormalities in patients with kidney stone disease. SUBJECTS AND METHODS: Clinical and biochemical data from 709 patients attending the Oxford University Hospitals NHS Foundation Trust for assessment and treatment of kidney stones were prospectively collected between April 2011 and February 2017. Data were analysed to determine the utility of serum calcium, parathyroid hormone (PTH), urate, chloride, bicarbonate, potassium and phosphate assays in screening for primary hyperparathyroidism, normocalcaemic hyperparathyroidism, hyperuricosuria, distal renal tubular acidosis (dRTA) and hypercalciuria. RESULTS: An elevated serum calcium level was detected in 2.3% of patients. Further investigations prompted by this finding resulted in a diagnosis of primary hyperparathyroidism in 0.2% of men and 4.6% of women for whom serum calcium was recorded. An elevated serum PTH level in the absence of hypercalcaemia was detected in 15.1% of patients. Of these patients, 74.6% were vitamin D-insufficient; no patients were diagnosed with normocalcaemic hyperparathyroidism. Hyperuricosuria was present in 21.6% of patients and hypercalciuria in 47.1%. Hyperuricaemia was not associated with hyperuricosuria, nor was hypophosphataemia associated with hypercalciuria. No patient was highlighted as being at risk of dRTA using serum chloride and bicarbonate as screening tests. CONCLUSION: This study indicates that individuals presenting with renal calculi should undergo metabolic screening with a serum calcium measurement alone. Use of additional blood tests to screen for metabolic disorders is not cost-effective and may provide false reassurance that metabolic abnormalities are not present. A full metabolic assessment with 24-h urine collection should be undertaken in recurrent stone formers and in those at high risk of future stone disease to identify potentially treatable metabolic abnormalities.

Predicting shockwave lithotripsy outcome for urolithiasis using clinical and stone computed tomography texture analysis variables.

We aimed to develop and evaluate a statistical model, which included known pre-treatment factors and new computed tomography texture analysis (CTTA) variables, for its ability to predict the likelihood of a successful outcome after extracorporeal shockwave lithotripsy (SWL) treatment for renal and ureteric stones. Up to half of patients undergoing SWL may fail treatment. Better prediction of which cases will likely succeed SWL will help patients to make an informed decision on the most effective treatment modality for their stone. 19 pre-treatment factors for SWL success, including 6 CTTA variables, were collected from 459 SWL cases at a single centre. Univariate and multivariable analyses were performed by independent statisticians to predict the probability of a stone free (both with and without residual fragments) outcome after SWL. A multivariable model had an overall accuracy of 66% on Receiver Operator Curve (ROC) analysis to predict for successful SWL outcome. The variables most frequently chosen for the model were those which represented stone size. Although previous studies have suggested SWL can be reliably predicted using pre-treatment factors and that analysis of CT stone images may improve outcome prediction, the results from this study have not produced a useful model for SWL outcome prediction.

Achieving Health Security and Threat Reduction through Sharing Sequence Data.

With the rapid development and broad applications of next-generation sequencing platforms and bioinformatic analytical tools, genomics has become a popular area for biosurveillance and international scientific collaboration. Governments from countries including the United States (US), Canada, Germany, and the United Kingdom have leveraged these advancements to support international cooperative programs that aim to reduce biological threats and build scientific capacity worldwide. A recent conference panel addressed the impacts of the enhancement of genomic sequencing capabilities through three major US bioengagement programs on international scientific engagement and biosecurity risk reduction. The panel contrasted the risks and benefits of supporting the enhancement of genomic sequencing capabilities through international scientific engagement to achieve biological threat reduction and global health security. The lower costs and new bioinformatic tools available have led to the greater application of sequencing to biosurveillance. Strengthening sequencing capabilities globally for the diagnosis and detection of infectious diseases through mutual collaborations has a high return on investment for increasing global health security. International collaborations based on genomics and shared sequence data can build and leverage scientific networks and improve the timeliness and accuracy of disease surveillance reporting needed to identify and mitigate infectious disease outbreaks and comply with international norms. Further efforts to promote scientific transparency within international collaboration will improve trust, reduce threats, and promote global health security.

A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa.

Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.

Mineralized collagen artificial bone repair material products used for fusing the podarthral joints with internal fixation-a case report.

In this study, we reported a case with collapse and subluxation of metatarsal-cuneiform joint, navicular-cuneiform joint with subluxed the right first metatarsophalangeal joint. The injured medial column was internally fixed with compression arthrodesis. The fusion site was firmed up with BonGold® Bone Sponge and Bone Putty. The prognosis of fused navicular-cuneiform joint and metatarsal-cuneiform joint were examined by X-ray shortly after surgical operation and followed up 2, 4, 6, 9 and 13 weeks after the surgical operation. The medial column was perfectly fused by compression arthrodesis. These results justified and favored the application of mineralized collagen as an excellent alternative to autograft in fusing the podarthral joints with internal fixation.

The Preoperative Assessment and Optimization of Patients Undergoing Major Urological Surgery.

PURPOSE OF REVIEW: Improving patient outcomes from major urological surgery requires not only advancement in surgical technique and technology, but also the practice of patient-centered, multidisciplinary, and integrated medical care of these patients from the moment of contemplation of surgery until full recovery. This review examines the evidence for recent developments in preoperative assessment and optimization that is of relevance to major urological surgery. RECENT FINDINGS: Current perioperative medicine recommendations aim to improve the short-term safety and long-term effectiveness of surgical treatments by the delivery of multidisciplinary integrated medical care. New strategies to deliver this aim include preoperative risk stratification using a frailty index and cardiopulmonary exercise testing for patients undergoing intra-abdominal surgery (including radical cystectomy), preoperative management of iron deficiency and anemia, and preoperative exercise intervention. Proof of the utility and validity for improving surgical outcomes through advances in preoperative care is still evolving. Evidence-based developments in this field are likely to benefit patients undergoing major urological surgery, but further research targeted at high-risk patients undergoing specific urological operations is required.

CT Texture Analysis of Ex Vivo Renal Stones Predicts Ease of Fragmentation with Shockwave Lithotripsy.

INTRODUCTION: Understanding the factors affecting success of extracorporeal shockwave lithotripsy (SWL) would improve informed decision-making on the most appropriate treatment modality for an individual patient. Although stone size and skin-to-stone distance do correlate with fragmentation efficacy, it has been shown that stone composition and architecture, as reflected by structural heterogeneity on CT, are also important factors. This study aims to determine if CT texture analysis (CTTA), a novel, nondestructive, and objective tool that generates statistical metrics reflecting stone heterogeneity, could have utility in predicting likelihood of SWL success. MATERIALS AND METHODS: Seven spontaneously passed, intact renal tract stones, were scanned ex vivo using standard CT KUB and micro-CT. The stones were then fragmented in vitro using a clinical lithotripter, after which, chemical composition analysis was performed. CTTA was used to generate a number of metrics that were correlated to the number of shocks needed to fragment the stone. RESULTS: CTTA metrics reflected stone characteristics and composition, and predicted ease of SWL fragmentation. The strongest correlation with number of shocks required to fragment the stone was mean Hounsfield unit (HU) density (r = 0.806, p = 0.028) and a CTTA metric measuring the entropy of the pixel distribution of the stone image (r = 0.804, p = 0.039). Using multiple linear regression analysis, the best model showed that CTTA metrics of entropy and kurtosis could predict 92% of the outcome of number of shocks needed to fragment the stone. This was superior to using stone volume or density. CONCLUSIONS: CTTA metrics entropy and kurtosis have been shown in this experimental ex vivo setting to strongly predict fragmentation by SWL. This warrants further investigation in a larger clinical study for the contribution of CT textural metrics as a measure of stone heterogeneity, along with other known clinical factors, to predict likelihood of SWL success.

In vitro and in vivo enhancement of osteogenic capacity in a synthetic BMP-2 derived peptide-coated mineralized collagen composite.

Enhancement of osteogenic capacity was achieved in a mineralized collagen composite, nano-hydroxyapatite/collagen (nHAC), by loading with synthetic peptides derived from BMP-2 residues 32-48 (P17-BMP-2). Rabbit marrow stromal cells (MSCs) were used in vitro to study cell biocompatibility, attachment and differentiation on the mineralized collagen composite by a cell counting kit, scanning electron microscopy (SEM) and real-time reversed transcriptase-polymerase chain reaction analysis (RT-PCR). Optimal peptide dosage (1.0 µg/mL) was obtained by RT-PCR analysis in vitro. In addition, the relative expression level of OPN and OCN was significantly upregulated on P17-BMP-2/nHAC compared with nHAC. In vitro results of P17-BMP-2 release kinetics demonstrated that nHAC released P17-BMP-2 in a controlled and sustained manner. In the rabbit mandibular box-shaped bone defect model, osteogenic capacity of three groups (nHAC, P17-BMP-2/nHAC, rhBMP-2/nHAC) was evaluated. Compared to the nHAC group, bone repair responses in both P17-BMP-2/nHAC and rhBMP-2/nHAC group implants were significantly improved based on histological analysis. The osteogenic response of the P17-BMP-2/nHAC group was similar to that of the rhBMP-2/nHAC group.

Building International Genomics Collaboration for Global Health Security.

Genome science and technologies are transforming life sciences globally in many ways and becoming a highly desirable area for international collaboration to strengthen global health. The Genome Science Program at the Los Alamos National Laboratory is leveraging a long history of expertise in genomics research to assist multiple partner nations in advancing their genomics and bioinformatics capabilities. The capability development objectives focus on providing a molecular genomics-based scientific approach for pathogen detection, characterization, and biosurveillance applications. The general approaches include introduction of basic principles in genomics technologies, training on laboratory methodologies and bioinformatic analysis of resulting data, procurement, and installation of next-generation sequencing instruments, establishing bioinformatics software capabilities, and exploring collaborative applications of the genomics capabilities in public health. Genome centers have been established with public health and research institutions in the Republic of Georgia, Kingdom of Jordan, Uganda, and Gabon; broader collaborations in genomics applications have also been developed with research institutions in many other countries.

Disappearing renal calculus.

We present a case of a renal calculus treated solely with antibiotics which has not been previously reported in the literature. A man with a 17 mm lower pole renal calculus and concurrent Escherichia coli urine infection was being worked up to undergo percutaneous nephrolithotomy. However, after a course of preoperative antibiotics the stone was no longer seen on retrograde pyelography or CT imaging.

Efficacy of the lithotripsy in treating lower pole renal stones.

Use of extracorporeal lithotripsy is declining in North America and many European countries despite international guidelines advocating it as a first-line therapy. Traditionally, lithotripsy is thought to have poor efficacy at treating lower pole renal stones. We evaluated the success rates of lithotripsy for lower pole renal stones in our unit. 50 patients with lower pole kidney stones ≤15 mm treated between 3/5/11 and 19/4/12 were included in the study. Patients received lithotripsy on a fixed-site Storz Modulith SLX F2 lithotripter according to a standard protocol. Clinical success was defined as stone-free status or asymptomatic clinically insignificant residual fragments (CIRFs) ≤3 mm at radiological follow-up. The mean stone size was 7.8 mm. The majority of stones (66 %) were between 5 and 10 mm. 28 % of stones were between 10 and 15 mm. For solitary lower pole stones complete stone clearance was achieved in 63 %. Total stone clearance including those with CIRFs was achieved in 81 % of patients. As expected, for those with multiple lower pole stones the success rates were lower: complete clearance was observed in 39 % and combined clearance including those with CIRFs was 56 %. Overall, complete stone clearance was observed in 54 % of patients and clearance with CIRFs was achieved in 72 % of patients. Success rate could not be attributed to age, stone size or gender. Our outcome data for the treatment of lower pole renal stones (≤15 mm) compare favourably with the literature. With this level of stone clearance, a non-invasive, outpatient-based treatment like lithotripsy should remain the first-line treatment option for lower pole stones. Ureteroscopy must prove that it is significantly better either in terms of clinical outcome or patient satisfaction to justify replacing lithotripsy.

Marked changes in body composition following neoadjuvant chemotherapy for oesophagogastric cancer.

BACKGROUND & AIMS: Patients with sarcopenia [reduced fat free mass (FFM)] have a higher incidence of chemotherapy-related toxicity and decreased survival. As there are no such data in patients with oesophagogastric cancer (OGC), this study investigated changes in body composition in OGC patients receiving neoadjuvant chemotherapy (NAC). METHODS: OGC patients who had CT scans before and after NAC were studied. CT images at the L3 vertebral level were analysed using SliceOmatic(®) software to derive estimates of FFM and fat mass (FM). Comparisons were made between pre- and post-NAC CT images. Data are reported as mean ± SD. RESULTS: Forty-seven patients (34 male) aged 63 ± 12 years were studied and 79% completed their course of NAC. The interval between CT scans was 107 ± 27 days. The proportion of patients with sarcopenia increased from 57% pre-NAC to 79% post-NAC (p = 0.046). During NAC there were significant reductions in estimated FFM and FM (2.9 ± 4.7 kg, p < 0.0001 and 1.3 ± 3.2 kg, p = 0.007, respectively). No association was demonstrated between loss of FFM and non-completion of NAC, increased hospital stay or mortality. CONCLUSIONS: In patients with OGC commencing NAC, sarcopenia was present in 57%. NAC was associated with further reductions in FFM and an increase in the proportion of patients becoming sarcopenic.

A prospective randomised study comparing oral 13C-bicarbonate tracer technique versus indirect calorimetry for measurement of energy expenditure in adults.

BACKGROUND AND AIMS: Accurate assessment of energy expenditure (EE) is important in guiding nutritional therapy but current methods are unsatisfactory. This study compared the oral 13C-bicarbonate tracer (BT) technique using the IRIS® system (Wagner, Germany) against indirect calorimetry (IC, ventilated-hood) to measure CO2 output (VCO2) and thus estimate EE. METHODS: Ten overnight-fasted healthy male volunteers were randomised to studies at rest or mild exercise in a crossover manner. During each study BT-IRIS® and IC were used simultaneously to measure VCO2 and thus EE. Participants ingested a drink labelled with 50mg 13C-bicarbonate and breath samples were collected every 5 min for 180 min and analysed using IRIS®. Bland-Altman plots were used to assess agreement between the two techniques in measurements of VCO2 (L/day) and estimates of EE (kJ/day). RESULTS: Mean ± SE age and BMI of participants were 21.1 ± 1.1 yrs and 23.6 ± 0.6 kg/m2. Both at rest and exercise, there was small bias but overall poor agreement between the two techniques as evident by the wide 95% limits of agreement in measurements of VCO2 and EE: rest VCO2 (bias 1.4, SD 93, 95% limits of agreement -180 to 183), rest EE (-8.3, 1830, -3595 to 3578), exercise VCO2 (49.3, 66.1, -80.4 to 178.9) and exercise EE (1083, 1944, -2727 to 4893). Furthermore, there was also evidence of systematic error in these measurements. CONCLUSION: Prior to clinical application, further optimisation of the BT-IRIS® system should be undertaken, given the poor agreement with IC in measuring VCO2 and estimating EE.

Reducing post-surgical adhesions utilizing a drug-enhanced device: sodium carboxymethylcellulose aqueous gel/poly(p-dioxanone) and Tranilast.

Post-surgical adhesion formation has numerous deleterious side effects in a wide variety of surgical settings. Physical barriers used together with laparoscopy were developed to reduce tissue trauma seen with open procedures. However, despite surgeons' meticulous techniques and the use of such barriers, adhesion formation remains a serious clinical problem, creating complications that cost the health care system over $1 billion annually. Our laboratories have combined a previously marketed drug, Tranilast, with a sodium carboxymethylcellulose (NaCMC) gel in a sustained release formulation using poly(p-dioxanone) (PDO) to provide a locally delivered medicated device that significantly reduces adhesions. This paper describes the preparation of the gel and the sustained release formulation, its key physical properties, and its sustained release kinetics. Pre-clinical data on inhibition of adhesion formation by the sustained release poly(p-dioxanone)/sodium carboxymethylcellulose/Tranilast drug enhanced device are also presented.

Reduction of post-surgical adhesion formation with tranilast.

BACKGROUND: Preclinical studies using the rabbit sidewall and double uterine horn models were used to assess time and dose response of tranilast delivered via subcutaneous pump, p.o., or as an intraperitoneal bolus in viscoelastic gels as well as an intraperitoneal biodegradable poly(p-dioxanone) fiber in reducing adhesions compared to vehicle controls. MATERIALS AND METHODS: New Zealand white rabbits underwent laparotomy followed by: 1) uterine horn abrasion and peripheral devascularization or 2) cecal abrasion and sidewall deperitonealization. Tranilast treatment using various vehicles and dosages was compared to vehicle alone versus no treatment. Animals were euthanized after 7 to 21 days. Adhesion formation was assessed by two independent observers. RESULTS: There were reductions in adhesion formation when drug was delivered topically, but oral drug alone was not effective. When tranilast was given preoperatively, oral drug added to the adhesion reduction of intraperitoneal administered drug. Tranilast in a viscoelastic carrier as well as in a biodegradable fiber was effective at reducing adhesions in the double uterine horn model. The slow release of tranilast from a biodegradable rod produced overall the best results. There were no safety issues. CONCLUSION: Tranilast was effective in reducing adhesions when given in a variety of vehicles in different rabbit models of adhesion formation. Overall, the sustained intraperitoneal delivery of tranilast from biodegradable fibers was the most suitable for clinical testing.

Mutagenesis and repair by low doses of alpha radiation in mammalian cells.

Low doses of alpha radiation in basements have been causally implicated in lung cancer. Previous studies have concentrated on high dose effects, for which no significant repair was found. In the present study, the methodology for measuring mutation by quantitating mitotic breaks and gaps was found to be applicable to G2-phase Chinese hamster ovary cells irradiated with 10-50 cGy of alpha radiation. The mutation yield in such cells closely resembles that of gamma irradiation. Caffeine, which inhibits repair, produces the same straight line increase of alpha and gamma mutation yields plotted against the dose. In the absence of caffeine, the repair of alpha radiation lesions is almost twice as great as for gamma radiation. Mitotic index changes substantiate these interpretations. It is proposed that the higher ion density associated with alpha radiation may result in fewer lesions being missed by the repair processes. The quantitation of chromosomal lesions for G2 cells exposed to low doses of alpha radiation, gamma radiation, or chemical mutagens in the presence and absence of caffeine is a rapid and reproducible methodology. Protection from mutational disease in a fashion similar to the use of sanitation for infectious disease appears practical.