Percutaneous radiofrequency ablation of renal cell carcinomas in patients with solitary kidney: 6 years experience

Objective

In this study we attempt to present our clinical experience in RFA under CT-guidance, in patients with renal cell carcinoma in a solitary kidney.

Material and Method

Between October 2000 and June 2005, 18 patients with solitary kidney and renal cell carcinoma underwent percutaneous CT-guided radiofrequency ablation in our institution. Tumors diameter ranged from 1 to 7 cm and there was no evidence of spread beyond the kidney. The RFA-system used was with expandable needle electrode (7 or 9 arrays). Technical success, recurrence and survival rate and complications were accessed. Patients were available for clinical and laboratory evaluation at a mean follow-up time of 31.2 months (range: 12–72 months).

Results

In all cases the electrode was successfully placed at the lesion. The 18 tumors were treated with totally 24 RFA sessions. In small (1–3 cm) exophytic tumors technical success was 85.7%. Residual disease was totally seen in 6/18 tumors which required a 2nd RFA session. The recurrence rate was 11.1% but no recurrence was noticed in tumors less than 3 cm in diameter. No major complications were observed. Serum creatinine values were normal in 17/18 patients till the 3rd-month follow-up. Survival ranged from 12 to 72 months.

Conclusion

RFA is an acceptable alternative for patients with small RCCs in a solitary kidney, which are not ideal candidates for surgical resection as their renal function must be preserved. They have an immediate solution to their clinical problem, under a minimally invasive therapy with no serious complications.     

Isotretinoin therapy induces DNA oxidative damage.

BACKGROUND: Isotretinoin (Iso) is currently indicated for the treatment of cystic acne (CA) and is related to marked teratogenicity. AIM: The aim of the study was to evaluate the relationship between total antioxidant status (TAS) and a serum marker of DNA oxidative damage, 8-hydroxy-2-desoxyguanosine (8-OHdG), in patients on Iso treatment. PATIENTS AND METHODS: Patients with CA (n=18) were evaluated before and 45 days after Iso (0.5 mg/kg per day) treatment and non-diseased controls (n=22) were tested only once. Plasma TAS levels and 8-OHdG were measured spectrophotometrically and with an immunoassay, respectively. Liver biochemical parameters and muscle enzymes were measured on a blood chemistry analyzer. RESULTS: TAS levels were significantly (p<0.0001) lower in patients before treatment (921+/-124 micromol/L) compared with those after treatment (1335+/-93 micromol/L) and in controls (1536+/-126 micromol/L). In contrast, 8-OHdG serum levels were two-fold higher in patients after treatment (0.21+/-0.03 ng/mL) than before treatment (0.11+/-0.02 ng/mL) and three-fold higher than in controls (0.07+/-0.01 ng/mL; p<0.0001). Negative correlations were found between TAS and 8-OHdG (r=-0.754, p<0.0001) in patients before therapy and positive correlations were found between creatine kinase (CK) and 8-OHdG (r=0.488, p<0.001) and liver enzymes after Iso treatment. CONCLUSIONS: High serum levels of 8-OHdG in patients on Iso therapy may be due to a direct effect of Iso on liver, muscle and skin epidermal cells. Regular evaluation of 8-OHdG in sera of patients, especially of women of reproductive age, on Iso treatment could be a sensitive follow-up biomarker of DNA oxidation.     

Developmental and adult phenotyping directly from mutant embryonic stem cells

Tetraploid embryo complementation assay has shown that mouse ES cells alone are capable of supporting embryonic development and adult life of mice. Newly established F(1) hybrid ES cells allow the production of ES cell-derived animals at a high enough efficiency to directly make ES cell-based genetics feasible. Here we report the establishment and characterization of 12 new F(1) hybrid ES cell lines and the use of one of the best (G4) in a gain- and loss-of-function genetic study, where the in vivo phenotypes were assessed directly from ES cell-derived embryos. We found the generation of G4 ES cell-derived animals to be very efficient. Furthermore, even after two consecutive rounds of genetic modifications, the majority of transgenic lines retained the original potential of the parental lines; with 10-40% of chimeras producing ES cell-derived animals/embryos. Using these genetically altered ES cells, this success rate, in most cases, permitted the derivation of a sufficient number of mutants for initial phenotypic analyses only a few weeks after the establishment of the cell lines. Although the experimental design has to take into account a moderate level of uncontrolled damage on ES cell lines, our proof-of-principle experiment provides useful data to assist future designs harnessing the power of this technology to accelerate our understanding of gene function.     

Vessel co‐option is common in human lung metastases and mediates resistance to anti‐angiogenic therapy in preclinical lung metastasis models

Anti‐angiogenic therapies have shown limited efficacy in the clinical management of metastatic disease, including lung metastases. Moreover, the mechanisms via which tumours resist anti‐angiogenic therapies are poorly understood. Importantly, rather than utilizing angiogenesis, some metastases may instead incorporate pre‐existing vessels from surrounding tissue (vessel co‐option). As anti‐angiogenic therapies were designed to target only new blood vessel growth, vessel co‐option has been proposed as a mechanism that could drive resistance to anti‐angiogenic therapy. However, vessel co‐option has not been extensively studied in lung metastases, and its potential to mediate resistance to anti‐angiogenic therapy in lung metastases is not established. Here, we examined the mechanism of tumour vascularization in 164 human lung metastasis specimens (composed of breast, colorectal and renal cancer lung metastasis cases). We identified four distinct histopathological growth patterns (HGPs) of lung metastasis (alveolar, interstitial, perivascular cuffing, and pushing), each of which vascularized via a different mechanism. In the alveolar HGP, cancer cells invaded the alveolar air spaces, facilitating the co‐option of alveolar capillaries. In the interstitial HGP, cancer cells invaded the alveolar walls to co‐opt alveolar capillaries. In the perivascular cuffing HGP, cancer cells grew by co‐opting larger vessels of the lung. Only in the pushing HGP did the tumours vascularize by angiogenesis. Importantly, vessel co‐option occurred with high frequency, being present in >80% of the cases examined. Moreover, we provide evidence that vessel co‐option mediates resistance to the anti‐angiogenic drug sunitinib in preclinical lung metastasis models. Assuming that our interpretation of the data is correct, we conclude that vessel co‐option in lung metastases occurs through at least three distinct mechanisms, that vessel co‐option occurs frequently in lung metastases, and that vessel co‐option could mediate resistance to anti‐angiogenic therapy in lung metastases. Novel therapies designed to target both angiogenesis and vessel co‐option are therefore warranted. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

How far are associations between child,family and community factors and child psychopathology informant‐specific and informant‐general?

Background:  Assessments of child psychopathology commonly rely on multiple informants, e.g., parents, teachers and children. Informants often disagree about the presence or absence of symptoms, reflecting reporter bias, situation-specific behaviour, or random variation in measurement. However, few studies have systematically tested how far correlates of child psychopathology differ between informants.
Methods:  Parents, teachers and children in the 1999 British Child and Adolescent Mental Health Survey ( n =  4,525, ages 11–15 years) completed the Strengths and Difficulties Questionnaire. Multiple source regression models tested the extent to which child, family, school and neighbourhood characteristics were differentially associated with the three informants' reports. The 2004 British Child and Adolescent Mental Health Survey ( n =  3,438, ages 11–15 years) was used for replication.
Results:  Almost all significant correlates of child mental health were differentially related to parent, teacher and child ratings of adjustment. Parental distress, parent-rated family functioning, and child physical health problems were most strongly associated with parent ratings. Child ability and attainment, socio-economic factors, and school and neighbourhood disadvantage were more strongly associated with teacher and parent rated mental health than with children's own ratings. Gender differences in externalising problems were most pronounced for teacher ratings, and least so for child ratings; the opposite held true for emotional problems. Effect sizes for combined latent scores fell near the upper end of the range of effect sizes estimated for the three individual informants. Results showed good replication across the two samples.
Conclusions:  The study highlights that there is substantial variation across informants in the links between associated factors and child psychopathology.     

Weight gain in gestational diabetes: the effect of treatment modality

Objective: To evaluate treatment effectiveness (diet alone, insulin or glyburide) on maternal weight gain in gestational diabetes (GDM).

Methods: GDM patients were treated with diet alone, insulin or glyburide. Weight gain was stratified into: prior to GDM diagnosis, from diagnosis to delivery and total pregnancy weight gain. Good glycemic control was defined as mean blood glucose ≤105?mg/dl and obesity as Body Mass Index (BMI)?≥?30?kg/m², overweight BMI 25–29?kg/m² and normal <?25?kg/m².

Results: Total weight gain was similar in all the treatment groups. Two-thirds of weight gain occurred prior to diagnosis (diet 85%, insulin 67% and glyburide 78%). Post-diagnosis, patients on diet alone gained less weight than those on insulin or glyburide (p?<?0.001); insulin-treated patients showed greater weight gain than glyburide-treated patients (p?<?0.001). Patients on diet with good glycemic control showed less weight gain after diagnosis than patients on insulin or glyburide (2.8?±?13, 6.6?±?10, 5.2?±?7.9 lbs, respectively, p?<?0.02). Poorly-controlled patients, regardless of treatment, had similar patterns of weight gain throughout pregnancy.

Conclusion: Patterns of maternal weight gain in GDM pregnancies are associated with treatment modality and level of glycemic control.     

An association between variants in the IGF2 gene and Beckwith-Wiedemann syndrome: interaction between genotype and epigenotype

Beckwith-Wiedemann syndrome (BWS) is a fetal overgrowth disorder involving the deregulation of a number of genes, including IGF2 and CDKN1C, in the imprinted gene cluster on chromosome 11p15.5. In sporadic BWS cases the majority of patients have epimutations in this region. Loss of imprinting of the IGF2 gene is frequently observed in BWS, as is reduced CDKN1C expression related to loss of maternal allele-specific methylation (LOM) of the differentially methylated region KvDMR1. The causes of epimutations are unknown, although recently an association with assisted reproductive technologies has been described. To date the only genetic mutations described in BWS are in the CDKN1C gene. In order to screen for other genetic predispositions to BWS, the conserved sequences between human and mouse differentially methylated regions (DMRs) of the IGF2 gene were analyzed for variants. Four single nucleotide polymorphisms (SNPs) were found in DMR0 (T123C, G358A, T382G and A402G) which occurred in three out of 16 possible haplotypes: TGTA, CATG and CAGA. DNA samples from a cohort of sporadic BWS patients and healthy controls were genotyped for the DMR0 SNPs. There was a significant increase in the frequency of the CAGA haplotype and a significant decrease in the frequency of the CATG haplotype in the patient cohort compared to controls. These associations were still significant in a BWS subgroup with KvDMR1 LOM, suggesting that the G allele at T382G SNP (CAGA haplotype) is associated with LOM at KvDMR1. This indicates either a genetic predisposition to LOM or interactions between genotype and epigenotype that impinge on the disease phenotype.