Recurrence of breast cancer after reconstruction with macro-textured silicone breast implants: A retrospective cohort study.

BACKGROUND: Recently, old concerns linking silicone breast implants (SBIs) with breast cancer have resurfaced. These concerns apply specifically to the risk of breast cancer recurrence in patients who received breast reconstructions with macro-textured SBIs. In this study, we investigated the effect of breast reconstruction with macro-textured SBIs on long-term oncologic outcomes of breast cancer patients. MATERIALS AND METHODS: We conducted a retrospective cohort study in two large cancer centres in the Netherlands. Patients who had been treated for primary breast cancer between January 1st 2000 and December 31st 2015 were included. Data on treatment and oncologic outcomes were obtained from prospectively maintained institutional and nationwide registries. Patient files were reviewed manually to complement missing information. Missing data was accounted for by multiple imputation by chained equations (MICE). Reconstruction with a macro-textured SBI was analysed as a time-dependent variable. The main outcomes of interest were locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS). Hazard Ratios (HRs) were estimated using multivariable Cox proportional hazard models. RESULTS: Of the 4,695 women who were eligible for inclusion, 2,393 had undergone mastectomy. Of these women, 1,187 (25%) had received breast reconstruction with a macro-textured SBI. Mean follow-up time was 11.5 (SD, 5.0) years. Compared with women who had undergone a simple mastectomy or autologous breast reconstruction, women with an implant-based reconstruction did not differ significantly in LRRFS or DMFS after accounting for various confounding factors (HR 1.27 [95% CI 0.93 - 1.72] and HR 0.94 [95% CI 0.74 - 1.20], respectively). Sensitivity analysis in complete cases of patients and varies subgroup analyses yielded similar results. CONCLUSION: Reassuringly, in this multi-centre cohort study no difference was found in long-term oncologic outcomes between women who had received breast reconstruction with a macro-textured SBI and women who had undergone a simple mastectomy or autologous breast reconstruction.

Strategies to increase survey participation: A randomized controlled study in a population of breast cancer survivors.

BACKGROUND: Data collection by mailing questionnaires to the study population is one of the main research methods in epidemiologic studies. As participation rates are decreasing, easy-to-implement and cost-effective strategies to increase survey participation are needed. In this study, we tested the effect of a pragmatic combination of evidence-based interventions. METHODS: We conducted a two-armed randomized controlled trial, nested in a cohort of breast cancer survivors (n = 1000) in the setting of a health outcomes survey. The intervention arm received a postal pre-notification, a non-monetary incentive (ballpoint with the study logo) and an alternative invitation letter in which several lay-out and textual adjustments were implemented according to behavioural science techniques. The alternative invitation letter also contained a QR-code through which an information video about the study could be accessed. The control arm was invited according to standard practice. Participants had the option to fill-out a questionnaire either on paper or online. A questionnaire with more than 50% of the questions answered classified as participation. RESULTS: Overall participation rate was 62.9%. No significant difference in participation rate was observed between intervention and control arm (64.5% vs 61.3%, Risk Ratio (RR) 1.05, 95% CI [0.96 - 1.16]). Older age at study (>65 vs <51 years), and high socio-economic status (highest vs lowest quartile) were associated with higher participation rates (RR 1.30, 95% CI [1.07 - 1.57] and 1.24, 95% CI [1.09 - 1.42] respectively). In-situ carcinoma compared to invasive cancer and longer interval since treatment were associated with lower participation (RR 0.86, 95% CI [0.74 - 0.99] and RR 0.92, 95% CI [0.87 - 0.99] per 5 year increase, respectively). CONCLUSION: Overall, the combination of four interventions tested in this study did not improve survey participation among breast cancer survivors. The overall participation rate was relatively high, possibly due to the study population of cancer survivors.

Intraoperative frozen section of subareolar tissue in nipple-sparing mastectomy: Towards a less is more approach.

BACKGROUND: Nipple preservation contributes to aesthetic outcome and quality of life in women undergoing Skin-Sparing Mastectomy (SSM) with immediate breast reconstruction for the treatment of breast cancer. Intraoperative Frozen Section (IFS) has been advocated to facilitate conversion from Nipple-Sparing Mastectomy (NSM) to SSM in cases with positive subareolar margins. This study investigated the application of IFS at our comprehensive cancer centre. METHODS: In this single-centre retrospective study, for all patients who underwent therapeutic NSM with IFS from 2000 to 2021 pathological reports, patient- and tumour characteristics were retrieved. RESULTS: In total 640 women were included in whom 662 intended NSMs with IFS had been performed. Sensitivity and specificity of frozen section compared with definitive histopathology were 75.2% and 98.5% respectively. In six women with a false positive result, the nipple had been removed. In 16 out of 32 women with a false negative result, the nipple was excised in a second procedure. In total 115 nipples were resected. In 40% of these nipples, no residual disease was detected. DISCUSSION: IFS is a moderately sensitive and highly specific diagnostic tool to detect positive subareolar margins. An alternative approach is to omit frozen section but take intraoperative biopsies of the sub areolar margin, which are postoperatively analysed with definitive formalin-fixed paraffin-embedded histopathology. This allows for shared decision making regarding nipple excision in cases where minimal disease is found in subareolar tissue or cases with an indication for post-mastectomy radiotherapy.

Historical Cohort of Severe Congenital Neutropenia in Iran: Clinical Course, Laboratory Evaluation, Treatment, and Survival.

INTRODUCTION: Severe congenital neutropenia (SCN) is one of the primary immunodeficiency diseases developed by genetic alterations. Mutations in several genes including HAX-1 , G6PC3 , jagunal , and VPS45 account for autosomal recessive SCN. PATIENTS AND METHODS: Patients with SCN registered in the Iranian Primary Immunodeficiency Registry and referred to our clinic at the Children's Medical Center were reviewed. RESULTS: Thirty-seven eligible patients with a mean age of 28.51 ± 24.38 months at the time of diagnosis were included. Nineteen cases had consanguineous parents and 10 cases had confirmed or unconfirmed positive family history. The most prevalent infectious symptoms were oral infections followed by respiratory infections. We identified HAX-1 mutation in 4, ELANE mutation in 4 cases, G6PC3 mutation in 1, and WHIM syndrome in 1 case. Other patients remained genetically unclassified. After the median follow-up of 36 months from the time of diagnosis, the overall survival was 88.88%. The mean event-free survival was 185.84 months (95% CI: 161.02, 210.66). DISCUSSION: Autosomal recessive SCN is more common in countries with high rates of consanguinity like Iran. The genetic classification was possible only for a few patients in our study. This might suggest that there are other autosomal recessive genes causative of neutropenia that have yet to be described.

The Areola study: design and rationale of a cohort study on long-term health outcomes in women with implant-based breast reconstructions.

BACKGROUND: Implant-based breast reconstructions contribute considerably to the quality of life of breast cancer patients. A knowledge gap exists concerning the potential role of silicone breast implants in the development of so-called "breast implant illness" (BII) and autoimmune diseases in breast cancer survivors with implant-based reconstructions. BII is a constellation of non-specific symptoms reported by a small group of women with silicone breast implants. METHODS: The Areola study is a multicenter retrospective cohort study with prospective follow-up aiming to assess the risk of BII and autoimmune diseases in female breast cancer survivors with and without silicone breast implants. In this report, we set out the rationale, study design, and methodology of this cohort study. The cohort consists of breast cancer survivors who received surgical treatment with implant-based reconstruction in six major hospitals across the Netherlands in the period between 2000 and 2015. As a comparison group, a frequency-matched sample of breast cancer survivors without breast implants will be selected. An additional group of women who received breast augmentation surgery in the same years will be selected to compare their characteristics and health outcomes with those of breast cancer patients with implants. All women who are still alive will be invited to complete a web-based questionnaire covering health-related topics. The entire cohort including deceased women will be linked to population-based databases of Statistics Netherlands. These include a registry of hospital diagnostic codes, a medicines prescription registry, and a cause-of-death registry, through which diagnoses of autoimmune diseases will be identified. Outcomes of interest are the prevalence and incidence of BII and autoimmune diseases. In addition, risk factors for the development of BII and autoimmune disorders will be assessed among women with implants. DISCUSSION: The Areola study will contribute to the availability of reliable information on the risks of BII and autoimmune diseases in Dutch breast cancer survivors with silicone breast implants. This will inform breast cancer survivors and aid future breast cancer patients and their treating physicians to make informed decisions about reconstructive strategies after mastectomy. REGISTRATION: This study is registered at ClinicalTrials.gov on June 2, 2022 (NCT05400954).

[Silicone breast implants: the importance of nuanced reporting]. / Siliconen borstimplantaten.

Silicone breast implants (SBIs) are frequently discussed in the media. Reporting on this topic is commonly characterised by sensationalism and a lack of nuance. SBIs have been linked to autoimmune disease and the controversial disease entity 'breast implant illness'. However, convincing evidence for this association is lacking because nearly all studies examining this association suffer from methodological weaknesses. Among the well-described long-term adverse effects of SBIs are implant ruptures, capsular contractures and the exceptionally rare breast implant-associated large cell lymphoma of the breast (BIA-ALCL). SBIs contribute significantly to the quality of life of many breast cancer patients and women with cosmetic implants. Any potential adverse effect of SBIs must therefore always be carefully weighed against the benefits of SBI-based procedures. In this consideration, evidence based on sound methodology is of vital importance. Oversimplified reporting based on deficient research leads to undue alarm among women with breast implants.

Liquid biopsy in esophageal cancer: a case report of false-positive circulating tumor DNA detection due to clonal hematopoiesis.

Circulating tumor DNA (ctDNA) analysis is a promising non-invasive technique for active surveillance after chemoradiotherapy for locally advanced resectable esophageal carcinoma. In other malignancies false-positive results in ctDNA analysis have been reported due to clonal hematopoiesis. In this case, we present a 66-year-old male who had adenocarcinoma of the gastroesophageal junction for which he received neoadjuvant chemoradiotherapy and underwent a transhiatal esophagectomy. Postoperatively our patient received follow-up with ctDNA analysis using next generation sequencing (NGS) and droplet digital PCR (ddPCR). This case report illustrates a number of the current challenges in ctDNA diagnostics in esophageal carcinoma. Firstly, the TP53 c.524G>A; p.R175H mutation that was found in preoperative tumor biopsies became detectable in ctDNA only after distant metastases had already been confirmed by clinical symptoms and standard imaging- and biopsy techniques. Secondly our patient repeatedly had false-positive outcomes of ctDNA analysis. Genomic analysis of white blood cells revealed that the origin of these discordant mutations lies in clonal hematopoiesis. Failure to detect TP53 c.524G>A; p.R175H in cell-free DNA (cfDNA) is most likely due to the amount of ctDNA in the cfDNA fraction being below the limit of detection for NGS and ddPCR analyses. Clinicians should be aware of the possibility of finding mutations originating from clonal hematopoiesis when using ctDNA analysis during active surveillance for esophageal carcinoma. We recommend correlation of mutations in cfDNA with mutations in tumor biopsies.

Congenital neutropenia and primary immunodeficiency diseases.

Neutropenia is a dangerous and potentially fatal condition that renders patients vulnerable to recurrent infections. Its severity is commensurate with the absolute count of neutrophil granulocytes in the circulation. In paediatric patients, neutropenia can have many different aetiologies. Primary causes make up but a small portion of the whole and are relatively unknown. In the past decades, a number of genes has been discovered that are responsible for congenital neutropenia. By perturbation of mitochondrial energy metabolism, vesicle trafficking or synthesis of functional proteins, these mutations cause a maturation arrest in myeloid precursor cells in the bone marrow. Apart from these isolated forms, congenital neutropenia is associated with a multiplicity of syndromic diseases that includes among others: oculocutaneous albinism, metabolic diseases and bone marrow failure syndromes. Congenital neutropenia is a primary immunodeficiency disease that is associated with recurrent bacterial infections, auto-inflammatory and auto-immune phenomena, haematological malignancy and neuro-psychiatric manifestations. The aim of this review is to give a comprehensive overview of the most recent literature concerning the clinical, aetiological and genetic features of congenital neutropenia and the syndromes in which it might be encountered.