Should we routinely analyze reduction mammaplasty specimens?

Background: Reduction mammaplasty is one of the most common plastic surgery procedures. Preoperative imaging and histopathology protocols vary among countries and institutions. We aimed to analyze the incidence of occult breast cancer and high-risk lesions in reduction mammaplasty specimens. We also analyzed whether patients with abnormal histopathology differed from the study population in terms of demographics. Patients and methods: In total, 918 women who underwent reduction mammaplasty from January 2007 to December 2011 were retrospectively reviewed for demographics, preoperative imaging, further preoperative examinations, pathology reports, and postoperative follow-up. Results: Abnormal histopathological findings were revealed in 88 (10%) patients with a mean age of 49.5 +/- 10.2 years. The incidence of breast cancer was 1.2%, and the incidence of high-risk lesions (atypical ductal and lobular hyperplasia and lobular carcinoma in situ) was 5.5%. Age and specimen weights were significantly higher in patients with abnormal histopathology. Eighty-one percent of patients with abnormal histopathology had normal preoperative imaging revealing two high-risk and two cancer findings. Two patients developed breast cancer in the same breast in which the high-risk lesion was originally detected. Conclusion: Women with abnormal histopathology cannot be sufficiently detected preoperatively. Therefore, histopathological analysis of reduction mammaplasty specimens seems mandatory. Reduction mammaplasty combined with subsequent histopathological examination offers a sufficient chance of detecting cancer and risk-increasing lesions that merits the cost of histopathology. (C) 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Breast Cancer Detection by Preoperative Imaging in Reduction Mammaplasty Patients : A Single Center Study of 918 Patients

Background The role of preoperative imaging and the usability of different imaging modalities is highly variable and controversial in reduction mammaplasty patients. Our study describes the imaging process in a single center in regard to modality selection, age and timing, and of the association between imaging and histopathological findings in reduction mammaplasty specimens. Methods Nine hundred eighteen women, who underwent reduction mammaplasty during 1.1.2007-31.12.2011, were retrospectively reviewed for demographics, preoperative imaging, further preoperative examinations, and pathology reports. Results Preoperative imaging had been conducted for 89.2% (n = 819) of the patients. In 49 (6.0%) patients, suspicious preoperative imaging led to further examinations revealing 2 high-risk lesions (atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS)), and 2 cancers preoperatively. Postoperatively abnormal histopathology specimens were revealed in 88 (10.4%) patients. The incidence of high-risk lesions was 5.5% (n = 47), and the incidence of cancer was 1.2% (n = 10). Preoperative imaging was normal (BI-RADS 1 and BI-RADS 2) in 80.8% of these patients. The sensitivity of the preoperative imaging for cancer detection was 20.0%, and the specificity was 100.0%. Conclusions Preoperative imaging and further examinations do not sufficiently detect malignant or cancer risk-increasing findings. Therefore, histopathological analysis of reduction mammaplasty specimens seems mandatory.Peer reviewe

Liver secretin receptor predicts portoenterostomy outcomes and liver injury in biliary atresia

Biliary atresia (BA) is a chronic neonatal cholangiopathy characterized by fibroinflammatory bile duct damage. Reliable biomarkers for predicting native liver survival (NLS) following portoenterostomy (PE) surgery are lacking. Herein we explore the utility of 22 preidentified profibrotic molecules closely connected to ductular reaction (DR) and prevailing after successful PE (SPE), in predicting PE outcomes and liver injury. We used qPCR and immunohistochemistry in a BA cohort including liver samples obtained at PE (n = 53) and during postoperative follow-up after SPE (n = 25). Of the 13 genes over-expressed in relation to cholestatic age-matched controls at PE, only secretin receptor (SCTR) expression predicted cumulative 5-year NLS and clearance of jaundice. Patients in the highest SCTR expression tertile showed 34–55% lower NLS than other groups at 1–5 years after PE (P = 0.006–0.04 for each year). SCTR expression was also significantly lower [42 (24–63) vs 75 (39–107) fold, P = 0.015] among those who normalized their serum bilirubin after PE. Liver SCTR expression localized in cholangiocytes and correlated positively with liver fibrosis, DR, and transcriptional markers of fibrosis (ACTA2) and cholangiocytes (KRT7, KRT19) both at PE and after SPE. SCTR is a promising prognostic marker for PE outcomes and associates with liver injury in BA

A new breast tomosynthesis imaging method: Continuous Sync-and-Shoot - technical feasibility and initial experience

Background Digital breast tomosynthesis (DBT) is gaining popularity in breast imaging. There are several different technical approaches for conducting DBT imaging. Purpose To determine optimal imaging parameters, test patient friendliness, evaluate the initial diagnostic performance, and describe diagnostic advances possible with the new Continuous Sync-and-Shoot method. Material and Methods Thirty-six surgical breast specimens were imaged with digital mammography (DM) and a prototype of a DBT system (Planmed Oy, Helsinki, Finland). We tested the patient friendliness of the sync-and-shoot movement without radiation exposure in eight volunteers. Different imaging parameters were tested with 20 specimens to identify the optimal combination: angular range 30 degrees, 40 degrees, and 60 degrees; pixel binning; Rhodium (Rh) and Silver (Ag) filtrations; and different kV and mAs values. Two breast radiologists evaluated 16 DM and DBT image pairs and rated six different image properties. Imaging modalities were compared with paired t-test. Results The Continuous Sync-and-Shoot method produced diagnostically valid images. Five out of eight volunteers felt no/minimal discomfort, three experienced mild discomfort from the tilting movement of the detector, with the motion being barely recognized. The combination of 30 degrees, Ag filtering, and 2 x 2 pixel binning produced the best image quality at an acceptable dose level. DBT was significantly better in all six evaluated properties (P < 0.05). Mean Dose(DBT)/Dose(DM) ratio was 1.22 (SD = 0.42). Conclusion The evaluated imaging method is feasible for imaging and analysing surgical breast specimens and DBT is significantly better than DM in image evaluation

Treatment and Prognosis of Radiation-Associated Breast Angiosarcoma in a Nationwide Population

Background Radiation-associated angiosarcoma of the breast (RAASB) is an aggressive malignancy that is increasing in incidence. Only a few previous population-based studies have reported the results of RAASB treatment. Methods A search for RAASB patients was carried out in the Finnish Cancer Registry, and treatment data were collected to identify prognostic factors for survival. Results Overall, 50 RAASB patients were identified. The median follow-up time was 5.4 years (range 0.4-15.6), and the 5-year overall survival rate was 69%. Forty-seven (94%) patients were operated on with curative intent. Among these patients, the 5-year local recurrence-free survival, distant recurrence-free survival, and overall survival rates were 62%, 75%, and 74%, respectively. A larger planned surgical margin was associated with improved survival. Conclusions We found that the majority of RAASB patients were eligible for radical surgical management in this population-based analysis. With radical surgery, the prognosis is relatively good.Peer reviewe

Variability of Care and Access to Transplantation for Children with Biliary Atresia Who Need a Liver Replacement

Background & Aims: Biliary atresia (BA) is the commonest single etiology indication for liver replacement in children. As timely access to liver transplantation (LT) remains challenging for small BA children (with prolonged waiting time being associated with clinical deterioration leading to both preventable pre- and post-transplant morbidity and mortality), the care pathway of BA children in need of LT was analyzed—from diagnosis to LT—with particular attention to referral patterns, timing of referral, waiting list dynamics and need for medical assistance before LT. Methods: International multicentric retrospective study. Intent-to-transplant study analyzing BA children who had indication for LT early in life (aged < 3 years at the time of assessment), over the last 5 years (2016–2020). Clinical and laboratory data of 219 BA children were collected from 8 transplant centers (6 in Europe and 2 in USA). Results: 39 patients underwent primary transplants. Children who underwent Kasai in a specialist -but not transplant- center were older at time of referral and at transplant. At assessment for LT, the vast majority of children already were experiencing complication of cirrhosis, and the majority of children needed medical assistance (nutritional support, hospitalization, transfusion of albumin or blood) while waiting for transplantation. Severe worsening of the clinical condition led to the need for requesting a priority status (i.e., Peld Score exception or similar) for timely graft allocation for 76 children, overall (35%). Conclusions: As LT currently results in BA patient survival exceeding 95% in many expert LT centers, the paradigm for BA management optimization and survival have currently shifted to the pre-LT management. The creation of networks dedicated to the timely referral to a pediatric transplant center and possibly centralization of care should be considered, in combination with implementing all different graft type surgeries in specialist centers (including split and living donor LTs) to achieve timely LT in this vulnerable population

Variability of Care and Access to Transplantation for Children with Biliary Atresia Who Need a Liver Replacement

Background & Aims: Biliary atresia (BA) is the commonest single etiology indication for liver replacement in children. As timely access to liver transplantation (LT) remains challenging for small BA children (with prolonged waiting time being associated with clinical deterioration leading to both preventable pre- and post-transplant morbidity and mortality), the care pathway of BA children in need of LT was analyzed-from diagnosis to LT-with particular attention to referral patterns, timing of referral, waiting list dynamics and need for medical assistance before LT. Methods: International multicentric retrospective study. Intent-to-transplant study analyzing BA children who had indication for LT early in life (aged < 3 years at the time of assessment), over the last 5 years (2016-2020). Clinical and laboratory data of 219 BA children were collected from 8 transplant centers (6 in Europe and 2 in USA). Results: 39 patients underwent primary transplants. Children who underwent Kasai in a specialist -but not transplant- center were older at time of referral and at transplant. At assessment for LT, the vast majority of children already were experiencing complication of cirrhosis, and the majority of children needed medical assistance (nutritional support, hospitalization, transfusion of albumin or blood) while waiting for transplantation. Severe worsening of the clinical condition led to the need for requesting a priority status (i.e., Peld Score exception or similar) for timely graft allocation for 76 children, overall (35%). Conclusions: As LT currently results in BA patient survival exceeding 95% in many expert LT centers, the paradigm for BA management optimization and survival have currently shifted to the pre-LT management. The creation of networks dedicated to the timely referral to a pediatric transplant center and possibly centralization of care should be considered, in combination with implementing all different graft type surgeries in specialist centers (including split and living donor LTs) to achieve timely LT in this vulnerable population.Peer reviewe

Variability of Care and Access to Transplantation for Children with Biliary Atresia Who Need a Liver Replacement

Background & Aims: Biliary atresia (BA) is the commonest single etiology indication for liver replacement in children. As timely access to liver transplantation (LT) remains challenging for small BA children (with prolonged waiting time being associated with clinical deterioration leading to both preventable pre- and post-transplant morbidity and mortality), the care pathway of BA children in need of LT was analyzed—from diagnosis to LT—with particular attention to referral patterns, timing of referral, waiting list dynamics and need for medical assistance before LT. Methods: International multicentric retrospective study. Intent-to-transplant study analyzing BA children who had indication for LT early in life (aged < 3 years at the time of assessment), over the last 5 years (2016–2020). Clinical and laboratory data of 219 BA children were collected from 8 transplant centers (6 in Europe and 2 in USA). Results: 39 patients underwent primary transplants. Children who underwent Kasai in a specialist -but not transplant- center were older at time of referral and at transplant. At assessment for LT, the vast majority of children already were experiencing complication of cirrhosis, and the majority of children needed medical assistance (nutritional support, hospitalization, transfusion of albumin or blood) while waiting for transplantation. Severe worsening of the clinical condition led to the need for requesting a priority status (i.e., Peld Score exception or similar) for timely graft allocation for 76 children, overall (35%). Conclusions: As LT currently results in BA patient survival exceeding 95% in many expert LT centers, the paradigm for BA management optimization and survival have currently shifted to the pre-LT management. The creation of networks dedicated to the timely referral to a pediatric transplant center and possibly centralization of care should be considered, in combination with implementing all different graft type surgeries in specialist centers (including split and living donor LTs) to achieve timely LT in this vulnerable population

Compressive stress-mediated p38 activation required for ER alpha plus phenotype in breast cancer

Breast cancer is now globally the most frequent cancer and leading cause of women's death. Two thirds of breast cancers express the luminal estrogen receptor-positive (ER alpha + ) phenotype that is initially responsive to antihormonal therapies, but drug resistance emerges. A major barrier to the understanding of the ER alpha-pathway biology and therapeutic discoveries is the restricted repertoire of luminal ER alpha + breast cancer models. The ER alpha + phenotype is not stable in cultured cells for reasons not fully understood. We examine 400 patient-derived breast epithelial and breast cancer explant cultures (PDECs) grown in various three-dimensional matrix scaffolds, finding that ER alpha is primarily regulated by the matrix stiffness. Matrix stiffness upregulates the ER alpha signaling via stress-mediated p38 activation and H3K27me3-mediated epigenetic regulation. The finding that the matrix stiffness is a central cue to the ER alpha phenotype reveals a mechanobiological component in breast tissue hormonal signaling and enables the development of novel therapeutic interventions. Subject terms: ER-positive (ER + ), breast cancer, ex vivo model, preclinical model, PDEC, stiffness, p38 SAPK. Reliable luminal estrogen receptor (ER alpha+) breast cancer models are limited. Here, the authors use patient derived breast epithelial and breast cancer explant cultures grown in several extracellular matrix scaffolds and show that ER alpha expression is regulated by matrix stiffness via stress-mediated p38 activation and H3K27me3-mediated epigenetic regulation.Peer reviewe

Incidence of Isolated Biliary Atresia during the COVID Lockdown in Europe: Results from a Collaborative Project by RARE-Liver

Background: Biliary atresia (BA) is a rare cholangiopathy where one of the proposed aetiological mechanisms is an infectious viral trigger. Coronavirus disease-19 (COVID) lockdown restrictions were implemented to reduce the transmission of infections. Strictness of lockdown varied across European countries. This study aimed to investigate if there was an association between strictness of lockdown and change in isolated BA (IBA) incidence in Europe. Methods: We approached European centres involved in the European Reference Network RARE-LIVER. We included IBA patients born between 2015 and June 2020. We calculated the number of IBA patients born per centre per month. The Stringency Index (SI) was used as lockdown strictness indicator. The association between percentage change of mean number of IBA patients born per month and the SI was assessed. Results: We included 412 IBA patients from thirteen different centres. The median number of patients per month did not change: 6 (1–15) pre-lockdown and 7 (6–9) during lockdown (p = 0.34). There was an inverse association between SI and percentage change in IBA (B = -0.73, p = 0.03). Median age at Kasai portoenterostomy (days) did not differ between time periods (51 (9–179) vs. 53 (19–126), p = 0.73). Conclusion: In this European study, a stricter COVID-lockdown was seemingly accompanied by a simultaneous larger decrease in the number of IBA patients born per month in the lockdown. Results should be interpreted with caution due to the assumptions and limitations of the analysis