Search

Abstract: Introduction: About 3–10% of breast cancer patients have distant metastases (Stage IV) at initial presentation; standard treatment (in the Netherlands) of these patients consists of palliative systemic therapy. However, retrospective studies have shown an improved survival in patients who received surgery for their primary tumor. The aim of this study was to assess characteristics associated with surgical treatment and to determine the impact on survival in women with stage IV breast cancer. Methods: A cohort of women with a diagnosis of breast cancer and concomitant distant metastases was retrospectively studied. Patient characteristics, treatment and survival distilled from medical files were evaluated using univariate and multivariable analysis. Results: Of 171 patients included in this analysis, 59 underwent surgery. In multivariable analysis lower age, no medication use, lower clinical T-stage and lower grade were associated with receiving surgery. In 21 of the 59 patients (35%) who received surgery it was unknown at the time of surgery that the patient had metastatic disease. Stratified survival analyses showed an association between surgery and improved survival for young patients (HR 0.3; p = 0.02), without comorbidity (HR 0.4; p = 0.002), with no medication use (HR 0.5; p = 0.009), with a small tumor (HR 0.4; p = 0.01), no regional lymph node involvement (HR 0.4; p = 0.01), with positive Estrogen (HR 0.6; p = 0.02) or Progesterone receptor (HR 0.4; p = 0.03) and with only visceral metastases (HR 0.5; p = 0.03). In multivariable analyses, younger patients and patients without comorbidity that received surgery had an increased survival (HR 0.3; p = 0.03 and HR 0.5; p = 0.03, respectively). Conclusion: This study showed that patients with the most favorable profile receive local surgery and that a survival gain for operated patients was seen in young patients and in patients without comorbidity. [Copyright &y& Elsevier]

Purpose: Preoperative partial breast irradiation (PBI) can increase accuracy of target volume definition and decrease irradiated volumes compared with postoperative PBI. In the ABLATIVE trial (NCT02316561), 15 of 36 patients achieved pathologic complete response 6 to 8 months after preoperative PBI and breast-conserving surgery (BCS). We now present the 5-year results., Methods and Materials: The ABLATIVE trial is a Dutch prospective cohort study conducted in 4 hospitals. Women aged ≥50 years with unifocal, nonlobular breast cancer, estrogen receptor-positive, HER2-negative, and a tumor negative sentinel node were treated between 2015 and 2018 with preoperative single-dose PBI followed by BCS after 6 or 8 months. The primary endpoint was pathologic complete response. Secondary endpoints were annually evaluated oncological outcomes, toxicity, cosmetic outcome (assessed by patients and physicians), and quality of life., Results: Thirty-six patients were treated with BCS 6 (n = 15) and 8 (n = 21) months following PBI. Median tumor size was 13 mm (IQR 9-16 mm). After a median follow-up of 5.5 years (IQR, 5.1-6.0), 2 (6%) patients had ipsilateral breast events and 2 (6%) distant metastases. The 5-year overall survival was 94% (95% CI, 87-100). The 5-year cumulative incidence of clinician-reported grade 1/2 breast fibrosis and breast discomfort/pain were 94%/6% and 75%/6%, respectively. The proportion of patients (very) satisfied with the cosmetic results was 89% at baseline and 78% at 5 years. Cosmetic results evaluated using the BCCT.core software were excellent or good in all patients. The 4-year median global quality of life score was 83 (IQR, 67-92), similar to baseline (83; IQR, 75-83; P = .42)., Conclusions: Preoperative single-dose PBI and BCS may be an oncologically safe treatment with mild late toxicity and no decline in cosmetic results and quality of life during 5 years of follow-up. This means that preoperative instead of standard postoperative irradiation has the potential to challenge the current clinical practice., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Breast cancer is the most common cancer in women, and breast reconstruction improves the patient's quality of life. Autologous breast reconstruction provides benefits of natural appearance, feel, and long-term results without implant-associated problems. However, thin patients are not always suitable for standard autologous reconstructions. In these patients, an omental flap could be a useful alternative. The aim of this review was to provide an overview of the literature regarding the clinical outcomes of omental flaps in breast reconstruction., Methods: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the Medline and Embase databases up to November 1, 2023. Study outcomes were type of flap, tissue transfer, cosmetic outcomes, and short- and long-term complications., Results: Eleven studies covering 985 reconstructions in 969 patients were included. The omentum was mostly laparoscopically harvested (88.6%) and a pedicled reconstruction was mostly performed (91.2%). The most commonly reported short-term complications were wound infections at the donor site (5.8%), partial flap necrosis, and fat necrosis. In the long term, epigastric, umbilical and tunnel hernias, and epigastric bulging were observed. Satisfactory cosmetic results were reported by the patients (88.7%) and professionals (80.0%)., Conclusion: Breast reconstruction using an omental flap can be performed in unilateral reconstructions with acceptable donor-site morbidity if laparoscopically harvested. In general, satisfactory cosmetic outcomes were reported and it appears to be a suitable alternative for selected patients who prefer autologous, unilateral breast reconstruction. Further research is necessary to determine the ideal candidates for this reconstruction and the long-term effects of an omentectomy in young patients., (© 2024 The Author(s).)

Background: Centralization of care jeopardizes interns' learning experiences and necessitates educational changes. Here we present the development and evaluation of a structured digital curriculum, offered in addition to the clinical internship, to address these challenges., Methods: The structured digital curriculum was implemented in a the VUmc/Amsterdam UMC surgical internship program in the Netherlands. The curriculum used a modular format built around a skill or clinical condition. Each module included background information, digital elements like e-learnings and interactive vlogs, and self-assessments. From April 1st to June 30th, 2022, we conducted a mixed-methods evaluation comparing interns' experiences between the conventional and digital curriculum through surveys and interviews., Results: Thirty-nine interns (28.1 %) completed the survey, 17 (24.2 %) from the traditional curriculum and 22 (31.9 %) from the structured blended curriculum. Results from the interviews triangulated and complemented survey results. Interns appreciated both curricula (course marks 7.4 ± 2.0 vs. 8.1 ± 1.1, P  = 0.207). The intervention cohort specifically appreciated the structured and comprehensive presentation of available study materials, which resulted in a sense of empowerment., Conclusions: Integrating a structured digital curriculum to support clinical internships provides interns with comprehensive, readily accessible knowledge, refines their understanding of clinical topics, and results in feelings of empowerment. The combination of clinical and digital education ensures adequate exposure to subjects vital for future doctors, even if clinical exposure is limited. Thus, using a structured digital curriculum prepares the intern and helps the internship program to adequately navigate future medical challenges., Key Message: Centralization of care jeopardizes interns' learning experiences and necessitates educational changes. A structured digital curriculum can empower interns in this scenario by providing readily accessible knowledge which refines their understanding of clinical topics., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Published by Elsevier Inc.)

Background: Laparoscopic incisional hernia repair is increasingly performed worldwide and expected to be superior to conventional open repair regarding hospital stay and quality of life (QoL). The INCisional Hernia-Trial was designed to test this hypothesis., Methods: A multicenter parallel randomized controlled open-label trial with a superiority design was conducted in six hospitals in the Netherlands. Patients with primary or recurrent incisional hernias were randomized by computer-guided block-randomization to undergo either conventional open or laparoscopic repair. Primary endpoint was postoperative length of hospital stay in days. Secondary endpoints included QoL, complications, and recurrences. Patients were followed up for at least 5 years., Results: Hundred-and-two patients were recruited and randomized. In total, 88 patients underwent surgery and were included in the intention-to-treat analysis (44 in the open group, 44 in the laparoscopic group). Mean age was 59.5 years, gender division was equal, and BMI was 28.8 kg/m. The trial was concluded early for futility after an unplanned interim analysis, which showed that the hypothesis needed to be rejected. There was no difference in primary outcome: length of hospital stay was 3 (range 1-36) days in the open group and 3 (range 1-12) days in the laparoscopic group (p = 0.481). There were no significant between-group differences in QoL questionnaires on the short and long term. Satisfaction was impaired in the open group. Overall recurrence rate was 19%, of which 16% in the open and 23% in the laparoscopic group (p = 0.25) at a mean follow-up of 6.6 years., Conclusions: In a randomized controlled trial, short- and long-term outcomes after laparoscopic incisional hernia repair were not superior to open surgery. The persisting high recurrence rates, reduced QoL, and suboptimal satisfaction warrant the need for patient's expectation management in the preoperative process and individualized surgical management., Trial Registration: Netherlands Trial Register NTR2808., (© 2023. The Author(s).)

Background: Coronavirus disease 2019 (COVID-19) patients can develop pulmonary fibrosis (PF), which is associated with impaired outcome. We assessed specific leukocytic transcriptome profiles associated with PF and the influence of early dexamethasone (DEXA) treatment on the clinical course of PF in critically ill COVID-19 patients., Methods: We performed a pre-post design study in 191 COVID-19 patients admitted to the Intensive Care Unit (ICU) spanning two treatment cohorts: the pre-DEXA- (n = 67) and the DEXA-cohort (n = 124). PF was identified based on radiological findings, worsening of ventilatory parameters and elevated circulating PIIINP levels. Longitudinal transcriptome profiles of 52 pre-DEXA patients were determined using RNA sequencing. Effects of prednisone treatment on clinical fibrosis parameters and outcomes were analyzed between PF- and no-PF-patients within both cohorts., Results: Transcriptome analyses revealed upregulation of inflammatory, coagulation and neutrophil extracellular trap-related pathways in PF-patients compared to no-PF patients. Key genes involved included PADI4, PDE4D, MMP8, CRISP3, and BCL2L15. Enrichment of several identified pathways was associated with impaired survival in a external cohort of patients with idiopathic pulmonary fibrosis. Following prednisone treatment, PF-related profiles reverted towards those observed in the no-PF-group. Likewise, PIIINP levels decreased significantly following prednisone treatment. PF incidence was 28% and 25% in the pre-DEXA- and DEXA-cohort, respectively (p = 0.61). ICU length-of-stay (pre-DEXA: 42 [29-49] vs. 18 [13-27] days, p < 0.001; DEXA: 42 [28-57] vs. 13 [7-24] days, p < 0.001) and mortality (pre-DEXA: 47% vs. 15%, p = 0.009; DEXA: 61% vs. 19%, p < 0.001) were higher in the PF-groups compared to the no-PF-groups within both cohorts. Early dexamethasone therapy did not influence these outcomes., Conclusions: ICU patients with COVID-19 who develop PF exhibit upregulated coagulation, inflammation, and neutrophil extracellular trap-related pathways as well as prolonged ICU length-of-stay and mortality. This study indicates that early dexamethasone treatment neither influences the incidence or clinical course of PF, nor clinical outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Preoperative instead of standard postoperative partial breast irradiation (PBI) after breast-conserving surgery (BCS) has the advantage of reducing the irradiated breast volume, toxicity, and number of radiotherapy sessions and can allow tumor downstaging. In this review, we assessed tumor response and clinical outcomes after preoperative PBI., Patients and Methods: We conducted a systematic review of studies on preoperative PBI in patients with low-risk breast cancer using the databases Ovid Medline, Embase.com, Web of Science (Core Collection), and Scopus (PROSPERO registration CRD42022301435). References of eligible manuscripts were checked for other relevant manuscripts. The primary outcome measure was pathologic complete response (pCR)., Results: A total of eight prospective and one retrospective cohort study were identified (n = 359). In up to 42% of the patients, pCR was obtained and this increased after a longer interval between radiotherapy and BCS (0.5-8 months). After a maximum median follow-up of 5.0 years, three studies on external beam radiotherapy reported low local recurrence rates (0-3%) and overall survival of 97-100%. Acute toxicity consisted mainly of grade 1 skin toxicity (0-34%) and seroma (0-31%). Late toxicity was predominantly fibrosis grade 1 (46-100%) and grade 2 (10-11%). Cosmetic outcome was good to excellent in 78-100% of the patients., Conclusions: Preoperative PBI showed a higher pCR rate after a longer interval between radiotherapy and BCS. Mild late toxicity and good oncological and cosmetic outcomes were reported. In the ongoing ABLATIVE-2 trial, BCS is performed at a longer interval of 12 months after preoperative PBI aiming to achieve a higher pCR rate., (© 2023. The Author(s).)

Background: Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients., Methods: The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy., Discussion: This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6-8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients., Trial Registration: The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722)., (© 2023. The Author(s).)

Data management in transmural care is complex. Without digital innovations like Health Information Exchange (HIE), patient information is often dispersed and inaccessible across health information systems between hospitals. The extent of information loss and consequences remain unclear. We aimed to quantify patient information availability of referred oncological patients and to assess its impact on unnecessary repeat diagnostics by observing all oncological multidisciplinary team meetings (MDTs) in a tertiary hospital. During 84 multidisciplinary team meetings, 165 patients were included. Complete patient information was provided in 17.6% (29/165, CI = 12.3-24.4) of patients. Diagnostic imaging was shared completely in 52.5% (74/141, CI = 43.9-60.9), imaging reports in 77.5% (100/129, CI = 69.2-84.2), laboratory results in 55.2% (91/165, CI = 47.2-62.8), ancillary test reports in 58.0% (29/50, CI = 43.3-71.5), and pathology reports in 60.0% (57/95, CI = 49.4-69.8). A total of 266 tests were performed additionally, with the main motivation not previously performed followed by inconclusive or insufficient quality of previous tests. Diagnostics were repeated unnecessarily in 15.8% (26/165, CI = 10.7-22.4) of patients. In conclusion, patient information was provided incompletely in majority of referrals discussed in oncological multidisciplinary team meetings and led to unnecessary repeat diagnostics in a small number of patients. Additional research is needed to determine the benefit of Health Information Exchange to improve data transfer in oncological care.

Background: Wire-guided localization (WGL) of early breast cancer can be facilitated using multiple wires, which is called bracketing wire-guided localization (BWL). The primary aim of this study is to compare BWL and conventional WGL regarding minimization of resection volumes without compromising margin status. Secondly, BWL is evaluated as an alternative method for intraoperative ultrasound (US) guidance in poorly definable breast tumors on US., Patients and Methods: In this retrospective cohort study, patients with preoperatively diagnosed breast cancer undergoing wide local excision between January 2016 and December 2018 were analyzed. Patients with multifocal disease or neoadjuvant treatment were excluded from this study. Optimal resection with minimal healthy breast tissue removal was assessed using the calculated resection ratio (CRR)., Results: BWL was performed in 17 (9%) patients, WGL in 44 (22%), and US in 139 (70%). The rate of negative margins was comparable in all 3 groups. The CRR was significantly smaller for BWL (0.6) than WGL (1.3) in tumors larger than 1.5 cm. Additionally, BWL (0.8) led to smaller CRRs than US (1.7). This could be explained by the high number of small tumors (≤ 1.5 cm) in the US group for which greater CRRs are obtained than for large tumors (> 1.5 cm) (1.9 vs. 1.4; P = .005)., Conclusion: For breast tumors larger than 1.5 cm, BWL achieves more optimal resection volumes without compromising margin status compared with WGL. Moreover, BWL seems a suitable alternative to US in patients with poorly ultrasound-visible breast tumors and patients with a small tumor in a (large) breast., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Real-time assessment of excised tissue may help to improve surgical results in breast tumor surgeries. Here, as a step towards this purpose, the potential of second and third harmonic generation (SHG, THG) microscopy is explored. SHG and THG are nonlinear optical microscopic techniques that do not require labeling of tissue to generate 3D images with intrinsic depth-sectioning at sub-cellular resolution. Until now, this technique had been applied on fixated breast tissue or to visualize the stroma only, whereas most tumors start in the lobules and ducts. Here, SHG/THG images of freshly excised unprocessed healthy human tissue are shown to reveal key breast components-lobules, ducts, fat tissue, connective tissue and blood vessels, in good agreement with hematoxylin and eosin histology. DNA staining of fresh unprocessed mouse breast tissue was performed to aid in the identification of cell nuclei in label-free THG images. Furthermore, 2- and 3-photon excited auto-fluorescence images of mouse and human tissue are collected for comparison. The SHG/THG imaging modalities generate high quality images of freshly excised tissue in less than a minute with an information content comparable to that of the gold standard, histopathology. Therefore, SHG/THG microscopy is a promising tool for real-time assessment of excised tissue during surgery., (© 2019 The Authors. Journal of Biophotonics published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction and Hypothesis: Abnormal postvoid residual volumes (PVRV) after delivery are common in daily clinical practice. By using an automatic scanning device, unnecessary catheterizations can be prevented. The aim of this study was to determine the accuracy of PVRV after vaginal delivery measured by an automatic scanning device through a comparison with transurethral catheterization., Materials and Methods: This prospective observational equivalence study was performed in patients who delivered vaginally between June 2012 and May 2017 in three teaching hospitals in The Netherlands. After the first spontaneous void after delivery, postvoid residual volume (PVRV) was measured with a portable automatic scanning device (BladderScan® BVI 9400). Directly afterward, it was measured by catheterization. Correlation between measurements was calculated using Spearman's correlation coefficient and agreement plot. The primary outcome was to validate the correlation between the BladderScan® compared with the gold standard of transurethral catheterization., Results: Data of 407 patients was used for final analysis. Median PVRV as measured by BladderScan® was 380 ml (± 261-0-999 ml) and by catheterization was 375 ml (± 315-1800 ml). Mean difference between measurements was -12.9 ml (± 178 ml). There was a very good correlation between methods (Spearman's rho = 0.82, p < 0.001). Using a cut-ff value of >500 ml, specificity and sensitivity were 85.4 and 85.6%, respectively., Conclusions: The BladderScan® (BVI 9400) measures PVRV precisely and reliably after vaginal delivery and should be preferred over catheterization.

Serpentinization, or the aqueous alteration of ultramafic rocks, results in challenging environments for life in continental sites due to the combination of extremely high pH, low salinity and lack of obvious electron acceptors and carbon sources. Nevertheless, certain Betaproteobacteria have been frequently observed in such environments. Here we describe physiological and genomic features of three related Betaproteobacterial strains isolated from highly alkaline (pH 11.6) serpentinizing springs at The Cedars, California. All three strains are obligate alkaliphiles with an optimum for growth at pH 11 and are capable of autotrophic growth with hydrogen, calcium carbonate and oxygen. The three strains exhibit differences, however, regarding the utilization of organic carbon and electron acceptors. Their global distribution and physiological, genomic and transcriptomic characteristics indicate that the strains are adapted to the alkaline and calcium-rich environments represented by the terrestrial serpentinizing ecosystems. We propose placing these strains in a new genus 'Serpentinomonas'.

Background: The number of elderly women with breast cancer is increasing and will become a major health concern. However, little is known about the optimal treatment for this age group. The aim of this study was to describe time trends for the overall Dutch breast cancer cohort with an emphasis on differences between young and elderly patients., Methods: All adult female patients diagnosed in 1995-2005 were selected from the Netherlands Cancer Registry. Relative excess risks for death (adjusted for stage, histology, treatment, and grade) were estimated using a multivariate generalized linear model with a Poisson distribution, based on collapsed relative survival data, using exact survival times., Results: Overall, 127,805 patients were included. Treatment of patients aged ≥75 years changed significantly over time: they received less surgery, more adjuvant hormonal treatment and chemotherapy, and more hormonal treatment without surgery. In contrast to younger patients, the relative survival did not improve significantly over time for elderly patients. With increasing age, the observed-expected death ratio decreased to almost 1.0., Conclusion: Survival for elderly patients with breast cancer did not improve significantly. Observed-expected death ratios in the elderly are close to 1, indicating that excess mortality is low. Elderly patients with breast cancer have a higher risk for overtreatment and undertreatment, with a delicate therapeutic balance between breast cancer survival gain and potential toxicities. To improve breast cancer survival in the elderly, a critical reappraisal is needed of costs and benefits of hormonal as well as other treatments, and better selection of patients who can benefit from available therapies is warranted.

Anaerobic consortia obtained from a wide variety of environments were tested for oxidizing several ecologically significant substrates with the humic model compound, anthraquinone-2,6-disulfonate (AQDS), as terminal electron acceptor. All the substrates, including hydrogen, acetate, propionate, methanol and lactate, were completely or partially converted to methane when bicarbonate was the only electron acceptor available. Addition of AQDS (20 mM) to the cultures prevented methanogenesis in most cases and AQDS reduction became the preferred pathway. AQDS was shown to be toxic for methanogenesis and this effect played an important role in enabling quinone-respiring bacteria to outcompete methanogens. Furthermore, AQDS respiration is thermodynamically more favorable than methanogenesis. All the consortia evaluated were capable of oxidizing hydrogen linked to the reduction of AQDS. Most inocula tested were also able to oxidize acetate and lactate in the same way. When methanol was provided as an electron donor competition between methanogenesis and acetogenesis occurred. Acetate accumulated from the latter process was responsible for quinone respiration. These results suggest that quinone-respiring bacteria are ubiquitous and that quinones in humus may significantly contribute to carbon cycling process by serving as a terminal electron acceptor for the anaerobic microbial oxidation of a wide variety of ecologically important substrates.

The capacity of anaerobic granular sludge for oxidizing phenol and p-cresol under anaerobic conditions was studied. Phenol and p-cresol were completely converted to methane when bicarbonate was the only terminal electron acceptor available. When the humic model compound, anthraquinone-2,6-disulfonate, was included as an alternative electron acceptor in the cultures, the oxidation of the phenolic compounds was coupled to the reduction of the model humic compound to its corresponding hydroquinone, anthrahydroquinone-2,6-disulfonate. These results demonstrate for the first time that the anaerobic degradation of phenolic compounds can be coupled to the reduction of quinones as terminal electron acceptor.