Management of phyllodes breast tumors

Phyllodes tumors are a rare distinctive fibroepithelial tumors of the breast and their management continues to be questioned. The aim of our study was to examine the treatment and outcome of 165 patients with phyllodes tumors and to review the options for surgical management. This is a retrospective study of 165 patients who presented to the Institut Curie between January 1994 and November 2008 for benign, borderline or malignant phyllodes tumors. The median follow-up was 12.65 months [range 0-149.8]. The median age at diagnosis was 44 years [range 17-79]. One hundred and sixty patients (97%) had breast-conserving treatment, of whom 3 patients (1.8%) had oncoplastic breast surgery. Younger women had a significantly higher chance of having a benign phyllodes tumor (p = 0.0001) or a tumor of small size (p < 0.0001). Histologic examination showed 114 benign (69%), 37 borderline (22%) and 14 malignant tumors (9%). The median tumor size was 30 mm [range 5-150]. The tumor margins were considered incomplete (< 10 mm) in 46 out of 165 cases (28%) with 52% revision surgery. Only the tumor grade was a significant risk factor for incomplete tumor margins (p = 0.005). Fifteen patients developed local recurrence (10%) and two, metastases. In univariate analysis, the histologic grade (p = 0.008), and tumor size (p = 0.02) were significative risk factors for local recurrence with an accentuated risk for "borderline" tumors and tumors of large size.).Similar results were obtained using multivariate analysis (p = 0.07). The mainstay of treatment for phyllodes tumors remains excision with a safe surgical margin, taking advantage breast conserving surgery where amenable. For borderline or malignant phyllodes tumors or in cases of local tumor recurrence, mastectomy, and immediate breast reconstruction may become the preferred option. Genetic analysis will potentially supplement classical histologic examination in order to improve our management of these tumors. The role of adjuvant treatments is unproven and must be considered on a case-by-case basis.     

Vascular renal anatomy and the ureteropelvic junction: preoperative multidetector CT scanning with split-bolus injection as a predictor of laparoscopic findings

PURPOSE: To compare multidetector CT scan (MDCT) results with intraoperative findings in the detection of an inferior-pole pedicle crossing the ureteropelvic junction. PATIENTS AND METHODS: Over the 2-year study period, 35 patients receiving laparoscopic pyeloplasty underwent preoperative investigation with a novel MDCT protocol in order to detect crossing vessels. Postprocessing, including maximum intensity projection, volume-rendering technique, and multiplanar reconstruction, was used in addition to standard axial views. RESULTS: All the arteries found during laparoscopic surgery were detected by MDCT, but one radiologic false-positive was noted at the beginning of the series. Seven veins were not detected with MDCT. In the only case featuring an isolated inferior-pole vein, the aberrant vessel was identified by MDCT. CONCLUSION: Multidetector CT scanning is a highly accurate way of providing all the information necessary preoperatively concerning renal parenchymal anomalies, urinary stones, and collecting system and vessel anatomy. It helps physicians make appropriate therapeutic decisions and gives surgeons information about what they can expect during laparoscopic procedures.     

Induced adiposity and adipocyte hypertrophy in mice lacking the AMP-activated protein kinase-alpha2 subunit

AMP-activated protein kinase (AMPK) is considered as a cellular energy sensor that regulates glucose and lipid metabolism by phosphorylating key regulatory enzymes. Despite the major role of adipose tissue in regulating energy partitioning in the organism, the role of AMPK in this tissue has not been addressed. In the present study, we subjected AMPKalpha2 knockout (KO) mice to a high-fat diet to examine the effect of AMPK on adipose tissue formation. Compared with the wild type, AMPKalpha2 KO mice exhibited increased body weight and fat mass. The increase in adipose tissue mass was due to the enlargement of the preexisting adipocytes with increased lipid accumulation. However, we did not observe any changes in adipocyte marker expression, such as peroxisome proliferator-activated receptor-gamma, CCAAT/enhancer-binding protein alpha (C/EBPalpha) and adipocyte fatty acid-binding protein (aFABP/aP2), or total cell number. Unlike impaired glucose homeostasis observed on normal diet feeding, when fed a high-fat diet AMPKalpha2 KO mice did not show differences in glucose tolerance and insulin sensitivity compared with wild-type mice. Our results suggest that the increase in lipid storage in adipose tissue in AMPKalpha2 KO mice may have protected these mice from further impairment of glucose homeostasis that normally accompanies high-fat feeding. Our study also demonstrates that lack of AMPKalpha2 subunit may be a factor contributing to the development of obesity.     

Functional quality of life following open valve surgery in high-risk octogenarians

Abstract Aim: The aim of this study was to determine the midterm functional quality of life in octogenarians after open valvular surgery. Methods: One hundred and eighty‐five consecutive patients above age 80 had valvular surgery with or without coronary artery bypass grafting (CABG). Using the Karnofsky Performance score and Barthel Index, patients were evaluated for functional autonomy, living disposition, and leisure activity by a single telephone interview. Subgroup analysis was performed on the 49 cases of isolated aortic valve replacement (AVR). Results: Mean age of octogenarians undergoing valvular surgery was 82.7 years (range 80 to 92 years). Actuarial survival at one and three years was 71% and 59%, respectively, for the entire group, compared to 84% and 71%, respectively, for isolated AVRs. After a mean follow‐up of 38 months there were 110 survivors (59.5%). Among survivors, 66% were autonomous, 26% semiautonomous, and 8% deemed dependent. Seventy‐two percent were living at home, 19% in a residence, and 9% in a supervised nursing facility. Over 90% of patients pursued leisure activities in the social, cognitive, and physical domains. Conclusions: Valvular surgery in high‐risk octogenarians, can be performed with acceptable mortality rates, and provide patients with functional autonomy and an excellent quality of life. (J Card Surg 2012;27:408‐414)     

Trends of lymphadenectomy in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy

Introduction

To evaluate temporal trends in the delivery and extent of lymphadenectomy (LND) in radical nephroureterectomy (RNU) performed in upper tract urothelial carcinoma (UTUC) patients.

Methods

We evaluated a multi institutional collaborative database composed by 1512 consecutive patients diagnosed with UTUC treated with RNU between 1990 and 2016. Year of surgery were grouped in five periods: 1990–1996, 1997–2002, 2003–2007, 2008–2012 and 2013–2016. Data about LND were available for all patients and numbers of nodes removed and positive were reported by dedicate uropathologists. The Mann–Whitney and Chi square tests were used to compare the statistical significance of differences in medians and proportions, respectively.

Results

Five hundred forty-five patients (36.0%) received a concomitant LND while 967 (64.0%) did not; 41.9% of open RNU patients received a concomitant LND compared to 24.4% of laparoscopic RNU patients. The rate of concomitant LND increased with time in the overall, laparoscopic and open RNU patients (all p?<?0.03). Patients treated with open RNU also had an increasing likelihood to receive an adequate concomitant LND (p?<?0.001) while those undergoing a laparoscopic approach did not (p?=?0.1). Patients treated with concomitant LND had a median longer operative time of 20 min (p?=?0.01). There were no differences in perioperative outcomes and complications between patients who received a concomitant LND and those who did not (p?>?0.1).

Conclusion

Although an increased trend was observed, most patients treated with RNU did not receive LND. Surgeons using a laparoscopic RNU were less likely to perform a concomitant LND, and when done, they remove less nodes.

     

Quantitative in vivo islet potency assay in normoglycemic nude mice correlates with primary graft function after clinical transplantation

Reliable assays are critically needed to monitor graft potency in islet transplantation (IT). We tested a quantitative in vivo islet potency assay (QIVIPA) based on human C-peptide (hCP) measurements in normoglycemic nude mice after IT under the kidney capsule. QIVIPA was initially tested by transplanting incremental doses of human islets. hCP levels in mice were correlated with the number of transplanted islet equivalents (r(2) = 0.6, P<0.01). We subsequently evaluated QIVIPA in eight islet preparations transplanted in type 1 diabetic patients. Conversely to standard criteria including islet mass, viability, purity, adenosine triphosphate content, or glucose stimulated insulin secretion, hCP in mice receiving 1% of the final islet product was correlated to primary graft function (hCP increase) after IT (r(2)=0.85, P<0.01). QIVIPA appears as a reliable test to monitor islet graft potency, applicable to validate new methods to produce primary islets or other human insulin secreting cells.     

Overexpression of FKBP51 in idiopathic myelofibrosis regulates the growth factor independence of megakaryocyte progenitors

Idiopathic myelofibrosis (IMF) is a chronic myeloproliferative disorder characterized by megakaryocyte hyperplasia and bone marrow fibrosis. Biologically, an autonomous megakaryocyte growth and differentiation is noticed, which contributes to the megakaryocyte accumulation. To better understand the molecular mechanisms involved in this spontaneous growth, we searched for genes differentially expressed between normal megakaryocytes requiring cytokines to grow and IMF spontaneously proliferating megakaryocytes. Using a differential display technique, we found that the immunophilin FKBP51 was 2 to 8 times overexpressed in megakaryocytes derived from patients' CD34(+) cells in comparison to normal megakaryocytes. Overexpression was moderate and confirmed in 8 of 10 patients, both at the mRNA and protein levels. Overexpression of FKBP51 in a UT-7/Mpl cell line and in normal CD34(+) cells induced a resistance to apoptosis mediated by cytokine deprivation with no effect on proliferation. FKBP51 interacts with both calcineurin and heat shock protein (HSP)70/HSP90. However, a mutant FKBP51 deleted in the HSP70/HSP90 binding site kept the antiapoptotic effect, suggesting that the calcineurin pathway was responsible for the FKBP51 effect. Overexpression of FKBP51 in UT-7/Mpl cells induced a marked inhibition of calcineurin activity. Pharmacologic inhibition of calcineurin by cyclosporin A mimicked the effect of FKBP51. The data support the conclusion that FKBP51 inhibits apoptosis through a calcineurin-dependent pathway. In conclusion, FKBP51 is overexpressed in IMF megakaryocytes and this overexpression could be, in part, responsible for the megakaryocytic accumulation observed in this disorder by regulating their apoptotic program.     

Backward masking during rapid serial visual presentation affects the amplitude but not the latency of the P3 event‐related potential

Masking of the first target in the attentional blink (AB) paradigm increases the magnitude of the AB relative to when the first target is not masked. We examined the underlying causes of this effect in an experiment in which a single target was presented in a rapid visual serial presentation stream. The P3 to the target was isolated by subtracting infrequent target category trials from frequent target category trials. The item immediately trailing the target (i.e., the mask) was present in the masked condition and replaced by a blank screen in the not‐masked condition, reproducing conditions known to modulate the AB. Masking the target significantly reduced the amplitude of the target‐locked P3 but had no effect on P3 latency. Results are discussed in relation to previous findings in the AB literature.