Prognostic role of ERCC1 protein expression in upper tract urothelial carcinoma following radical nephroureterectomy with curative intent

Background

Excision repair cross-complementing 1 (ERCC1) has been associated with outcomes of urothelial carcinoma of the bladder, but was not yet studied in upper tract urothelial carcinoma (UTUC). The aim of this study was to assess the prognostic role of ERCC1 expression in a large international cohort of UTUC patients.

Methods

Immunohistochemical ERCC1 expression was evaluated in 716 UTUC patients who underwent radical nephroureterectomy with curative intent. ERCC1 was considered positive when the H-score was >1.0. Associations with overall survival and cancer-specific survival were assessed using univariable and multivariable Cox models.

Results

ERCC1 was expressed in 303 tumors (42.3 %) and linked with the presence of tumor necrosis (16.2 vs. 10.4 %, p = 0.023), but not with any other clinical or pathological variable. ERCC1 status did not predict cancer-specific survival and overall survival on both univariable (p = 0.70 and 0.32, respectively) and multivariable analyses (p = 0.48 and 0.33, respectively).

Conclusions

ERCC1 is expressed in a significant proportion of UTUC and is linked with tumor necrosis, but its expression appears not to be associated with prognosis following radical nephroureterectomy.

     

Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children

CD31(+)CD45RA(+)RO(-) lymphocytes contain high numbers of T cell receptor circle (TREC)-bearing T cells; however, the correlation between CD31(+)CD4(+) lymphocytes and TREC during aging and under lymphopenic conditions has not yet been sufficiently investigated. We analyzed TREC, telomere length and telomerase activity within sorted CD31(+) and CD31(-) CD4(+) lymphocytes in healthy individuals from birth to old age. Sorted CD31(+)CD45RA(+)RO(-) naive CD4(+) lymphocytes contained high TREC numbers, whereas CD31(+)CD45RA(-)RO(+) cells (comprising < or =5% of CD4(+) cells during aging) did not contain TREC. CD31(+) overall CD4(+) cells remained TREC rich despite an age-related tenfold reduction from neonatal (100 : 1000) to old age (10 : 1000). Besides a high TREC content, CD31(+)CD45RA(+)RO(-)CD4(+) cells exhibited significantly longer telomeres and higher telomerase activity than CD31(-)CD45RA(+)RO(-)CD4(+) cells, suggesting that CD31(+)CD45RA(+)RO(-)CD4(+) cells represent a distinct population of naive T cells with particularly low replicative history. To analyze the value of CD31 in lymphopenic conditions, we investigated six children after allogeneic hematopoietic stem cell transplantation (HSCT). Reemerging overall CD4(+) as well as naive CD45RA(+)RO(-)CD4(+) cells predominantly expressed CD31 and correlated well with the recurrence of TREC 5-12 months after HSCT. Irrespective of limitations in the elderly, CD31 is an appropriate marker to monitor TREC-rich lymphocytes essentially in lymphopenic children after HSCT.     

Prise en charge d’un patient adulte atteint de mucoviscidose

The authors describe the case report of a patient with cystic fibrosis. The nutritional management is discussed during the different stages of disease treatment and progression.     

Advances in computational modeling approaches of pituitary gonadotropin signaling

Introduction: Pituitary gonadotropins play an essential and pivotal role in the control of human and animal reproduction within the hypothalamic–pituitary–gonadal (HPG) axis. The computational modeling of pituitary gonadotropin signaling encompasses phenomena of different natures such as the dynamic encoding of gonadotropin secretion, and the intracellular cascades triggered by gonadotropin binding to their cognate receptors, resulting in a variety of biological outcomes.

Areas covered: The authors provide an overview of the historical and ongoing issues in modeling and data analysis related to gonadotropin secretion in the field of both physiology and neuroendocrinology. They mention the different mathematical formalisms involved, their interest and limits. They also discuss open statistical questions in signal analysis associated with key endocrine issues and review recent advances in the modeling of the intracellular pathways activated by gonadotropins, which yields promising development for innovative approaches in drug discovery.

Expert opinion: The greatest challenge to be tackled in computational modeling of pituitary gonadotropin signaling is the embedding of gonadotropin signaling within its natural multi-scale environment, from the single cell level, to the organic and whole HPG level. The development of modeling approaches of G protein-coupled receptor signaling, together with multicellular systems biology may lead to unexampled mechanistic understanding with critical expected fallouts in the therapeutic management of reproduction.     

Longitudinal cohort study on preoperative pain as a risk factor for chronic postoperative inguinal pain after groin hernia repair at 2-year follow-up

Hernia - To assess the rate of late chronic postoperative inguinal pain (CPIP) after groin hernia repair in patients with different categories of preoperative VRS (Verbal Rating Scale) pain and to...     

MRI-targeted biopsy for detecting prostate cancer: have the guidelines changed our practices and our prostate cancer detection rate?

International Urology and Nephrology - In our center, until 2018, MRI-targeted biopsy was underused. Since January 2018, we systematically performed MRI-targeted biopsy for suspicious...     

Does surgical approach influence mid- to long-term patient-reported outcomes after primary total hip replacement? A comparison of the 3 main surgical approaches

BackgroundThe most effective surgical approach to total hip replacement (THR) remains controversial. Most studies that have compared approaches have reported only short-term outcome data. It is therefore unclear in the literature if a particular surgical approach offers long-term advantages. The aim of this study was to determine the effect of the 3 main surgical approaches to THR on patient-reported outcomes 5 years after surgery.MethodsAll patients who underwent a THR for osteoarthritis or osteonecrosis between 2008 and 2012 by an anterior, posterior or lateral approach at The Ottawa Hospital in Ontario, Canada, were included in the study. All preoperative and postoperative scores for the Hip Disability and Osteoarthritis Outcome Score (HOOS) and Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) questionnaires were recorded. Analysis of covariance was used to study the relationship between the amount of change in scores on the HOOS and WOMAC subscales (dependent variables) and the surgical approach. The confounding factors of age, sex, American Society of Anesthesiologists (ASA) class, Charnley classification and body mass index were included in the analysis.ResultsThere were 138 patients (37.6%) in the posterior approach group, 104 (28.3%) in the lateral approach group and 125 (34.1%) in the anterior approach group. There were no significant differences among the 3 groups in terms of Charnley classification, body mass index, sex, ASA class, surgical side and preoperative functional scores. We did not observe any significant differences in the amount of change in the scores for HOOS and WOMAC subscales among the 3 groups. There were also no differences in the final postoperative scores.ConclusionOur findings suggest that the choice of surgical approach in primary THR surgery without revision has no influence on functional outcomes and quality of life after 5 years. Further studies are needed to assess how patient age and sex may influence the functional outcome of individual surgical approaches.     

Diagnostic markers of postoperative morbidity after laparoscopic Roux-en-Y gastric bypass for obesity

Purpose

The main objective of this study was to detect subacute complications that can arise from laparoscopic Roux-en-Y gastric bypass and take a rational approach to manage these complications.

Methods

A prospective observational study was performed from November 2010 to December 2012. All patients undergoing gastric bypass surgery for morbid obesity were included in this study. Patients with complications before day 5 were excluded from the study. Clinical and laboratory data (C-reactive protein, leukocyte count) at postoperative day 5, 30-day morbidity, were recorded. The diagnostic value of C-reactive protein (CRP) and leukocytes were determined by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.

Results

One hundred and twenty-six patients were included. The overall incidence of 30-day morbidity was 8.7 %, and anastomotic leakage rate was 3.2 %. C-reactive protein at postoperative day 5 was a good predictor of complications (AUC was 0.862 (95 % CI [0.76; 0.96]; p?<?0.001) and anastomotic leakage (AUC was 0.863 (95 % CI [0.66; 1]; p?=?0.014). A CRP cutoff level of 136 mg/l at postoperative day 5 yielded a specificity of 95.5 % and a sensitivity of 57.1 % for the detection of postoperative complications. The negative predictive value was 94.6 %. A CRP level of 136 mg/l at day 5 was significantly associated with postoperative morbidity.

Conclusions

C-reactive protein dosage at postoperative day 5 is a relevant predictor of postoperative complications permitting to select patients at risk. Radiological examination and close monitoring could be restricted to patients with CRP level exceeding 136 mg/l.