Alterations in Breast Cancer Biomarkers Following Neoadjuvant Therapy

Annals of Surgical Oncology - Biomarker changes in patients with residual disease (RD) after neoadjuvant systemic therapy (NAT) have unclear consequences. This study examined the prevalence of...     

Differential contribution of the factors determining long-term renal function after partial nephrectomy over time

PurposeTo define how much of renal function was determined by the preserved renal parenchymal volume and the ischemic insult during partial nephrectomy (PN) long after surgery.MethodsWe analyzed the data of 530 consecutive patients who had undergone PN. For all patients, renal function was measured preoperatively and again at 3 postoperative months, then annually using ^99mTc-diethylenetriaminepentaacetic acid renal scan. Perioperative variables potentially affecting the long-term ipsilateral glomerular filtration rate (GFR) and their time-varying contribution were assessed using a linear mixed model.ResultsThe mean preoperative ipsilateral GFR was 42.9 ml/min, which decreased by 27.3% at 3 months but began to recover thereafter continuing until 4 years (Δ% GFR at 1, 2, 3, 4, and 5 years: 22.3%, 18.5%, 14.7%, 10.0%, and 9.6%, respectively). Parenchymal volume reduction and ischemic time were significantly associated with postoperative ipsilateral GFR throughout observation period unvarying with time. Diabetes and proteinuria were not significant determinants of ipsilateral function at 3 months but became significant at 5 years. In multivariate analysis regarding recovery slope, volume reduction (β = ?0.026, SE 0.006, P < 0.0001), preoperative ipsilateral GFR (β = ?0.021, SE 0.007, P = 0.0012), proteinuria (β = ?0.942, SE 0.372, P = 0.0116), and diabetes (β = ?0.396, SE 0.197, P = 0.0447) were independently significant.ConclusionIpsilateral renal function continued to improve until 5 years after PN. Parenchymal volume loss was the major determinant and its impact on long-term ipsilateral renal function remained constant while ischemic time affected early GFR reduction with its impact diminishing over time. Patient-related factors including diabetes and proteinuria gained significance over time and became independent determinants of recovery slope.     

A prognostic immune predictor,HLA-DRA,plays diverse roles in non-muscle invasive and muscle invasive bladder cancer

BackgroundThere is an increasing demand for prognostic immune biomarkers of cancer. The prognostic significance of immune markers has been shown for various cancers, but biomarkers of bladder cancer (BCa) have not been fully evaluated. To clarify the role of human leukocyte antigen DR alpha chain (HLA-DRA) in BCa development, we examined expression of HLA-DRA mRNA in tissue samples of non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC).Materials and MethodsTissues of 96 NMIBC, 43 MIBC and 59 controls comprising noncancerous BCa surrounding tissues were used to examine the expression of HLA-DRA gene by real-time polymerase chain reaction. The expression of up-stream genes regulating HLA-DRA were also measured to explain the role of HLA-DRA in BCa.ResultsPatients with high grade NMIBC showed higher expression of HLA-DRA than those with low grade NMIBC (P < 0.05). In addition, NMIBC patients who progressed to MIBC showed high expression of HLA-DRA mRNA. Kaplan-Meier analysis showed that NMIBC patients with low expression of HLA-DRA had better progression-free survival than those with high expression (P = 0.004). Moreover, the expression of genes regulating HLA-DRA varied in NMIBC and MIBC, indicating a different immunoregulation effect of HLA-DRA in both cancers.ConclusionsHigh expression of HLA-DRA in NMIBC patients has implications for patient stratification strategies, as well as for BCa tumor immunology.     

STAG2 as a prognostic biomarker in low-grade non-muscle invasive bladder cancer

ObjectiveImprovements to bladder cancer risk stratification guidelines are needed to better tailor post-operative surveillance and adjuvant therapy to individual patients. We previously identified STAG2 as a commonly mutated tumor suppressor gene in bladder cancer and an independent predictor of progression in NMIBC. Here we test the value of combining STAG2 immunostaining with other risk stratification biomarkers in NMIBC, and as an individual biomarker in MIBC.Materials and MethodsSTAG2 immunohistochemistry was performed on a progressor-enriched cohort of tumors from 297 patients with NMIBC, and on tumors from 406 patients with MIBC from Aarhus University Hospital in Denmark. Survival analysis was performed using Kaplan-Meier survival analysis, the log rank test, and Cox proportional hazards models.ResultsSTAG2-negative low-grade NMIBC tumors were 2.5 times less likely to progress to muscle invasion than STAG2-positive low-grade NMIBC tumors (Log-rank test, P = 0.008). In a composite group of patients with AUA intermediate and high-risk NMIBC tumors, STAG2-negative tumors were less likely to progress (Log-rank test, P = 0.02). In contrast to NMIBC, we show that STAG2 is not useful as a prognostic biomarker in MIBC.ConclusionsSTAG2 immunostaining can be used to subdivide low-grade NMIBC tumors into two groups with substantially different risks of disease progression. Furthermore, STAG2 immunostaining may be useful to enhance NMIBC risk stratification guidelines, though larger cohorts are needed to solidify this conclusion in individual risk groups. STAG2 is not useful as a biomarker in MIBC. Further study of the use of STAG2 immunostaining as a biomarker for predicting the clinical behavior in NMIBC is warranted.     

Computed Tomography Evaluation of Forearm and Hand Muscles in Patients With Distal Radius Fracture

Introduction: Computed tomography (CT) can be used to assess bone status with measurement of Hounsfield unit (HU). The objective of this study was to evaluate whether HU of muscle might be associated with parameters of bone and muscle status. Methods: We reviewed 71 women aged over 50 yr of age who had distal radius fracture and underwent CT evaluation of affected wrist. We assessed HUs of forearm flexor muscles (flexor digitorum superficialis) and thenar muscles and bone HUs at the capitate and the ulnar head. Other parameters included femur neck and lumbar bone mineral density (BMD), upper extremity lean mass, hand grip strength, and muscle fiber cross-sectional area. We performed correlation analyses to determine associations between variables. Results: Thenar and forearm muscle HUs were significantly correlated with each other, but not with other parameters. HUs of the capitate and ulnar head were positively correlated with femur neck and lumbar BMDs and inversely correlated with age. Ulnar head HU was positively correlated hand grip strength. Conclusions: HUs of forearm and thenar muscles did not show significant correlations with bone or muscle parameters, although bone HUs correlated well with bone mineral densities. These results support the opportunistic use of CT for evaluating bone fragility. Clinical usefulness of muscle HU measurement needs further studies.     

Adverse events involving hallux metatarsophalangeal joint implants: Analysis of the United States Food and Drug Administration data from 2010 to 2018

BackgroundThe prevalence of osteoarthritis of the hallux metatarsophalangeal joint (MTPJ) is 1 in 40 people over the age of 50. Surgical treatment options for MTPJ arthritis include joint preservation, joint resurfacing, and arthrodesis. Hallux MTPJ implants have evolved over the past several decades, but are associated with various complications. The aim of this study was to examine the MAUDE database to determine reported adverse events for hallux MTPJ implants.Materials and methodsThe US Food and Drug Administration’s (FDA) Manufacturer and User Facility Device Experience (MAUDE) database was reviewed from 2010 to 2018 to review voluntary reported adverse event reports for approved implants within the United States. We recorded the type of adverse event and excluded duplicate reports and those extracted from already published literature.ResultsAmong 64 reported hallux MTPJ implant adverse events, the most common modes of adverse events were component loosening (34%), infection (14.1%), component fracture (9.4%), inflammation (9.4%), and allergic reaction (7.8%). Regarding implant type, Cartiva SCI had the highest percentage of adverse events (23.4%), followed by Arthrosurface ToeMotion (20.3%), Ascension MGT (12.5%), Arthrosurface HemiCAP® (10.9%), Futura primus (9.4%), and Osteomed Reflexion (6.3%). There was an increase in reported adverse events after 2016. The MAUDE database does not report the total incidence of implant insertion.ConclusionOur study of the MAUDE database demonstrated that component loosening and infection are the most common modes of adverse events for hallux MTPJ implants. Cartiva accounted for one-fourth of the implant-related adverse events during our study period, followed by ToeMotion, and Ascension MGT implants. Continued reporting of adverse events will improve our understanding on short and long-term complications of various hallux MTPJ implants.Level of evidenceLevel IV; Case Series from Large Database Analysis; Treatment Study.     

Double hernia in continuous ambulatory peritoneal dialysis patient

Clinical and Experimental Nephrology -