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BACKGROUND: Post-operative pancreas fistula (POPF) is a common complication after pancreatoduodenectomy (PD). A Teres Ligamentum (TL)-wrap covering the pancreaticojejunostomy (PJ) is suggested as a potential solution to reduce POPF. The aim of this study was to compare POPF incidence (grade B/C) in patients with or without a TL-wrap.METHODS: A prospective cohort study was performed between January 2019-December 2021. All consecutive patients were included. Patient, tumor and surgical characteristics and postoperative complications were compared in both open and robot-assisted surgery.RESULTS: A total of 118 consecutive patients were included. The first 57 patients were treated without and the following 61 patients with a TL-wrap. There were no statistically significant differences between both groups regarding patient, pre-operative treatment and surgical characteristics. The occurrence of POPF was strongly reduced in the TL-wrap group compared to patients without a TL-wrap (3.3% vs 28.1%, P < 0.001). Also mean length of hospital stay was reduced (11.5 vs 18.8 days, P = 0.030).CONCLUSION: The use of a TL-wrap covering the PJ as addition to the modified Blumgart anastomosis technique is associated with a significantly reduced POPF rate and a reduced length of hospital stay. A TL-wrap is a simple addition to a PJ that may be considered to improve postoperative outcome. This association must be studied more definitively in a randomized controlled trial.

Background There is a transition from wire-guided localization (WGL) of non-palpable breast cancer to other localization techniques. Multiple prospective studies have sought to establish superior clinical outcomes for radioactive-seed localization (RSL), but consistent and congruent evidence is missing. Methods In this study, female patients with breast cancer operated with breast-conserving surgery after tumour localization of a non-palpable breast cancer or ductal carcinoma in situ (DCIS) were included. The cohort was identified from the nationwide Netherlands Breast Cancer Audit conducted between 2013 and 2018. Trends in localization techniques were analysed. Univariable and multivariable analyses were performed to assess the association between the localization technique and the probability of a reoperation. Results A total of 28 370 patients were included in the study cohort. The use of RSL increased from 15.7 to 61.1 per cent during the study years, while WGL decreased from 75.4 to 31.6 per cent. The localization technique used (RSL versus WGL) was not significantly associated with the odds of a reoperation, regardless of whether the lesion was DCIS (odds ratio 0.96 (95 per cent c.i. 0.89 to 1.03; P = 0.281)) or invasive breast cancer (OR 1.02 (95 per cent c.i. 0.96 to 1.10; P = 0.518)). Conclusion RSL is rapidly replacing WGL as the preoperative localization technique in breast surgery. This large nationwide registry study found no association between the type of localization technique and the odds of having a reoperation, thus confirming the results of previous prospective cohort studies.

Background: Data on effectiveness and optimal use of neoadjuvant endocrine therapy (NET) in clinically biopsy-proven node-positive breast cancer is lacking. This study examined the incidence of axillary pathological complete response (pCR) on NET in clinically biopsy-proven node-positive breast cancer patients. Secondary, patient and tumour characteristics, as well as the optimal duration of NET in relation to the occurrence of axillary pCR were investigated.Material and methods: Patients diagnosed with primary hormone receptor positive, HER2 negative breast cancer between 2014 and 2019, with at least one positive axillary lymph node (pathologically proven), treated with NET were selected from the Netherlands Cancer Registry. The incidence of axillary pCR in combination with patient, tumour and treatment characteristics was analysed.Results: In a population of 561 patients, an axillary pCR of 7.3% on NET was observed. Median length of treatment was 8.1 months in the patients without vs. 8.8 months in those with axillary pCR, with no statistically significant difference. A p-value

Background In line with the paradigm to minimize surgical morbidity in patients with primary breast cancer, there is increasing evidence for the safety of a repeat breast-conserving treatment (BCT) of an ipsilateral breast tumour recurrence (IBTR) in selected patients. The conditions for the feasibility of a repeat BCT vary widely in literature. In clinical practice, many physicians have ongoing concerns about the oncological safety and possible toxicity of repeat BCT. Aim To investigate the attitude of Dutch breast surgeons and radiation oncologists towards repeat BCT and to report on their experiences with, objections against and perceived requirements to consider a repeat BCT in case of IBTR. Patients and methods An online survey consisting of a maximum of 26 open and multiple-choice questions about repeat BCT for IBTR was distributed amongst Dutch breast surgeons and radiation oncologists. Results Forty-nine surgeons representing 49% of Dutch hospitals and 20 radiation oncologists representing 70% of Dutch radiation oncology centres responded. A repeat BCT was considered feasible in selected cases by 28.7% of breast surgeons and 55% of radiation oncologists. The most important factors to consider a repeat BCT for both groups were the patient’s preference to preserve the breast and surgical feasibility of a second lumpectomy. Arguments against a repeat BCT were based on the perceived unacceptable toxicity and cosmesis of a second course of radiotherapy. The technique of preference for re-irradiation would be partial breast irradiation (PBI) according to all radiation oncologists. Differentiating between new primary tumours (NPT) and true recurrences (TR) was reported to be done by 57.1% of breast surgeons and 60% of radiation oncologists. The most important reason to differentiate between NPT and TR was to establish prognosis and to consider whether a repeat BCT would be feasible. Conclusion An increasing number of Dutch breast cancer specialists is considering a repeat BCT feasible in selected cases, at the patient’s preference and with partial breast re-irradiation.

Background Despite increasingly effective curative breast-conserving treatment (BCT) regimens for primary breast cancer, patients remain at risk for an ipsilateral breast tumor recurrence (IBTR). With increasing interest for repeat BCT in selected patients with IBTR, a reliable assessment of the size of IBTR is important for surgical planning. Aim The primary aim of this study is to establish the performance in size estimation of XMG, US, and breast MRI in patients with IBTR. The secondary aim is to compare the detection of multifocality and contralateral lesions between XMG and MRI. Patients and methods The sizes of IBTR on mammography (XMG), ultrasound (US), and magnetic resonance imaging (MRI) in 159 patients were compared to the sizes at final histopathology. The accuracy of the size estimates was addressed using Pearson’s coefficient and Bland–Altman plots. Secondary outcomes were the detection of multifocality and contralateral lesions between XMG and MRI. Results Both XMG and US significantly underestimated the tumor size by 3.5 and 4.8 mm, respectively, while MRI provided accurate tumor size estimation with a mean underestimation of 1.1 mm. The sensitivity for the detection of multifocality was significantly higher for MRI compared to XMG (25.5% vs. 5.5%). A contralateral malignancy was found in 4.4% of patients, and in 1.9%, it was detected by MRI only. Conclusion The addition of breast MRI to XMG and US in the preoperative workup of IBTR allows for more accurate size estimation. MRI provides a higher sensitivity for the detection of multifocality compared to XMG.

Objectives To investigate whether breast MRI has comparable diagnostic performance as dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer. Methods Forty-seven patients were included. All had undergone both breast MRI and dedicated axillary MRI, followed by surgery. All included breast MRI exams had complete field of view (FOV) of the axillary region. First, unenhanced T2-weighted (T2W) and subsequent diffusion-weighted (DW) images of both MRI exams were independently analyzed by two breast radiologists using a confidence scale and compared to histopathology. ADC values were measured by two researchers independently. Diagnostic performance parameters were calculated on a patient-by-patient basis. Results T2W breast MRI had the following diagnostic performance: sensitivity of 50.0% and 62.5%, specificity of 92.3%, PPV of 57.1% and 62.5%, NPV of 90.0% and 92.3%, and AUC of 0.72 for reader 1 and 0.78 for reader 2. T2W dedicated axillary MRI had the following diagnostic performance: sensitivity of 37.5% and 62.5%, specificity of 82.1% and 92.3%, PPV of 44.6% and 50.0%, NPV of 87.8% and 91.4%, and AUC of 0.65 for reader 1 and 0.73 for reader 2. In both evaluations, addition of DW images resulted in comparable diagnostic performance. For both breast MRI and dedicated axillary MRI, there was no significant difference between mean ADC values of benign and malignant lymph nodes. Conclusions T2W breast MRI with complete FOV of the axillary region has comparable diagnostic performance as T2W dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer. Optimization of T2W breast MRI protocol by including a complete FOV of the axillary region can, therefore, be recommended in clinical practice. Key Points • Breast MRI with complete field of view of the axillary region has comparable diagnostic performance as dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer. • Optimization of breast MRI protocol by including a complete field of view of the axillary region is recommended in clinical practice. • For both breast MRI and dedicated axillary MRI, DW imaging (including ADC measurements) is of no added value.

The standard of care for patients with an ipsilateral breast tumour recurrence (IBTR) after breast-conserving therapy (BCT) is a salvage mastectomy. However, there is growing interest in the feasibility of repeat BCT for these patients. This systematic review contains the latest insights on BCT options for patients with an IBTR after initial BCT. A PubMed literature search was performed for articles on BCT options for IBTR after primary lumpectomy followed by radiotherapy. Weighted estimates were calculated for 5- and 10-year local control, distant metastasis-free and overall survival rates. Secondary outcomes were toxicity, cosmesis and quality of life. In total, 34 studies were eligible for analysis, of which 5 reported on repeat breast-conserving surgery (BCS) alone, 10 with mixed populations (BCS +/- RT and/or mastectomy), 18 on repeat BCS followed by re irradiation (whole-breast or partial) and one on quality of life. The weighted estimates for 5-year overall survival for repeat BCS and repeat BCS followed by reirradiation were 77% and 87%, respectively. Five-year local control was 76% for repeat BCS alone and 89% for repeat BCS followed by re-irradiation. Grade III-IV toxicity rates after re-irradiation varied from 0 to 21%, whereas the cosmesis was excellent-good in 29-100% of patients and unacceptable in 0-18%. Repeat BCS followed by re-irradiation, with either whole breast or partial breast re-irradiation, seems a feasible alternative to mastectomy in case of IBTR, in selected patients. Toxicity rates are low and the cosmetic outcome is good, but the size and follow-up of the published patient series is limited. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Introduction: Imaging findings can be affected by histopathological characteristics, such as breast cancer subtypes. The aim was to determine whether the diagnostic performance, in particular negative predictive value (NPV), of axillary US differs per subtype of breast cancer.Methods: All patients diagnosed between 2008 and 2016 in our hospital with primary invasive breast cancer and an axillary US prior to axillary surgery were included. Histopathology of axillary surgery specimens served as gold standard. The NPV, sensitivity, specificity, positive predictive value (PPV) and accuracy of the axillary US were determined for the overall population and for each subtype (ER+/PR+HER2-,HER2+, triple negative tumors). The Chi-square test was used to determine the difference in diagnostic performance parameters between the subtypes.Results: A total of 1094 breast cancer patients were included. Of these, 35 were diagnosed with bilateral breast cancer, resulting in 1129 cancer cases. Most common subtype was ER+/PR+HER2- in 858 cases (76.0%), followed by 150 cases of HER2+ tumors (13.3%) and 121 cases of triple negative tumors (10.7%). Sensitivity, specificity and accuracy of axillary US did not significantly differ between the subtypes. There was a significant difference for NPV between triple negative tumors and HER2+ tumors (90.3% vs. 80.2%, p = 0.05) and between HER2+ and ER/PR+HER2- tumors (80.2% vs. 87.2%, p = 0.04).Conclusion: There was no significant difference in the diagnostic performance of axillary US between the subtypes, except for NPV. This was highest in triple negative subtype and lowest in HER2+ tumors. This can be explained by the difference in prevalence of axillary lymph node metastases in our cohort. (C) 2019 Published by Elsevier Ltd.

Aim To evaluate the diagnostic performance for margin assessment of specimen radiography (SR) in breast conserving surgery (BCS) using radioactive I125-seed localization (RSL). Methods The clinical, radiographic and histopathological data of women who underwent BCS after pre-operative RSL with intraoperative SR during nine consecutive years were analyzed. The histological margin and radiographic margin outcomes on SR were compared and results of intraoperative re-excisions were investigated. Results A consecutive series of 448 women with invasive carcinoma (n = 211), ductal carcinoma in situ (DCIS) (n = 79) and a combination of DCIS and invasive carcinoma (n = 158) were included. The median minimal margins for the radiological masses and microcalcifications measured on SR were 14 mm and 11 mm, respectively. Based on a radiological cut-off SR margin value of 1 mm, the overall sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were 21.0%, 95.0%, 26.0%, and 94.0%, respectively. The area under the receiver-operating curve was 0.73. Intraoperative re-excisions based on SR were performed in 31 (6.9%) patients; histopathological examination of the additional excised tissue revealed DCIS or invasive carcinoma in 6 (19.4%) patients. Hence, SR was beneficial for 6/448 patients (1.3%), and unnecessary intraoperative re-excisions were performed in 20/448 patients (4.5%). The number need to treat is 75; this implies that per 75-SR one resection with involved margins is prevented. Conclusion SR has a moderate diagnostic performance for margin involvement using RSL. A more accurate intraoperative margin assessment tool is warranted.

Background: The incidence and clinical significance of multifocality in ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) are unclear. With growing interest in repeat BCT, this information has become of importance. This study aimed to gain insight in the incidence of multifocality in IBTR, to identify patient- and tumor-related predicting factors and to investigate the prognostic significance of multifocality.Methods: Two hundred and fifteen patients were included in this analysis. All had an IBTR after BCT and were treated by salvage mastectomy and appropriate adjuvant therapy. Predictive tumor- and patient-related factors for multifocality in IBTR were identified using X2 test and univariate logistic regression analyses. Prognostic outcomes were calculated using Kaplan Meier analysis and compared using the log rank test.Results: Multifocality was present in 50 (22.9%) of IBTR mastectomy specimens. Axillary positivity in IBTR was significantly associated with multifocality in IBTR. Chest wall re-recurrences occurred more often after multifocal IBTR (14% versus 7% after unifocal IBTR, p = 0.120). Regional re-recurrences did not differ significantly between unifocal and multifocal IBTR (8% vs. 6%, p = 0.773). Distant metastasis after salvage surgery occurred more frequently after multifocal IBTR (15% vs. 24%, p = 0.122). Overall survival was 132 months after unifocal IBTR and 112 months after multifocal IBTR (p = 0.197).Conclusion: The prevalence of multifocality in IBTR is higher than in primary breast cancer. Axillary positivity in IBTR was associated with a multifocal IBTR. Chest wall re-recurrences and distant metastasis were, although not statistically significant, more prevalent after multifocal IBTR. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Objectives To compare standard breast MRI to dedicated axillary ultrasound (with or without tissue sampling) for differentiating between no, limited and advanced axillary nodal disease in breast cancer patients. Methods All patients who underwent breast MRI and dedicated axillary ultrasound between 2009 and 2014 were eligible. Exclusion criteria were recurrent disease, neoadjuvant systemic therapy and not receiving completion axillary lymph node dissection after positive sentinel lymph node biopsy (SLNB). Two radiologists independently reassessed all MRI exams. Axillary ultrasound findings were retrospectively collected. Probability of advanced axillary nodal disease (pN2-3) given clinically node negative (cN0) or limited (cN1) findings was calculated, with corresponding negative predictive value (NPV) to exclude pN2-3 and positive predictive value (PPV) to identify axillary nodal disease. Histopathology served as gold standard. Results A total of 377 cases resulted in 81.4% no, 14.4% limited and 4.2% advanced axillary nodal disease at final histopathology. Probability of pN2-3 given cN0 for breast MRI and axillary ultrasound was 0.7–0.9% versus 1.5% and probability of pN2-3 given cN1 was 11.6–15.4% versus 29.0%. When cN1 on breast MRI was observed, PPV to identify positive axillary nodal disease was 50.7% and 59.0%. Conclusions Evaluation of axillary nodal status on standard breast MRI is comparable to dedicated axillary ultrasound in breast cancer patients. In patients who underwent preoperative standard breast MRI, axillary ultrasound is only required in case of suspicious nodal findings on MRI.

Preoperative differentiation between limited (pN1; 1–3 axillary metastases) and advanced (pN2–3; ≥4 axillary metastases) nodal disease can provide relevant information regarding surgical planning and guiding adjuvant radiation therapy. The aim was to evaluate the diagnostic performance of preoperative axillary ultrasound (US) and breast MRI for differentiation between pN1 and pN2–3 in clinically node-positive breast cancer. A total of 49 patients were included with axillary metastasis confirmed by US-guided tissue sampling. All had undergone breast MRI between 2008–2014 and subsequent axillary lymph node dissection. Unenhanced T2-weighted MRI exams were reviewed by two radiologists independently. Each lymph node on the MRI exams was scored using a confidence scale (0–4) and compared with histopathology. Diagnostic performance parameters were calculated for differentiation between pN1 and pN2–3. Interobserver agreement was determined using Cohen’s kappa coefficient. At final histopathology, 67.3% (33/49) and 32.7% (16/49) of patients were pN1 and pN2–3, respectively. Breast MRI was comparable to US in terms of accuracy (MRI reader 1 vs US, 71.4% vs 69.4%, p = 0.99; MRI reader 2 vs US, 73.5% vs 69.4%, p = 0.77). In the case of 1–3 suspicious lymph nodes, pN2–3 was observed in 30.4% on US (positive predictive value (PPV) 69.6%) and in 22.2–24.3% on MRI (PPV 75.7–77.8%). In the case of ≥4 suspicious lymph nodes, pN1 was observed in 33.3% on US (negative predictive value (NPV) 66.7%) and in 38.5–41.7% on MRI (NPV 58.3–61.5%). Interobserver agreement was considered good (k = 0.73). In clinically node-positive patients, the diagnostic performance of axillary US and breast MRI is comparable and limited for accurate differentiation between pN1 and pN2–3. Therefore, there seems no added clinical value of preoperative breast MRI regarding nodal staging in patients with positive axillary US.

Background: The proportion of elderly women diagnosed with breast cancer is rising. Standard treatment, including axillary staging, is often not given to these patients. This study aimed to investigate reasons to omit any surgical axillary staging or to refrain from completion axillary lymph node dissection (cALND) after positive-sentinel lymph node biopsy (SLNB); so-called "incomplete staging". Furthermore, the impact of incomplete staging on regional control and survival in patients aged 75 or older was evaluated.Methods: A retrospective cohort study was conducted including all primary breast cancer patients aged 75 or older, diagnosed between 2001 and 2008, and documented by the Netherlands Cancer Registry (NCR). Patients with incomplete staging were compared to patients with complete axillary staging. Survival analyses were used to determine the risk of local, regional and distant recurrence and overall survival.Results: In total, 1467 of 2116 (69%) patients were considered eligible, of whom 258 (17.2%) had incomplete axillary staging. For 93 patients, diagnosed in 6 of the 10 hospitals in the NCR-area, examination of clinical records revealed that age, comorbidities and patient preferences were the main reason for omitting complete axillary staging. The 10-year axillary recurrence rate in these 93 patients was 5.2% (95% CI, 0.03-10.1). Of the 77 patients who had died, 64 (83%) died of non-breast-cancer-related causes. No significant difference in overall survival was observed between patients with or without complete axillary staging.Conclusion: This study demonstrates that the omission of complete axillary staging is common in selected elderly breast cancer patients with >= 2 comorbidities, with no apparent impact on regional control and 10-year overall survival. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

AIM: To evaluate diagnostic performance of gadofosveset ( GDF)-enhanced magnetic resonance imaging (MRI) in addition to T2-weighted (T2W) MRI for nodal (re) staging in newly diagnosed breast cancer patients. MATERIALS AND METHODS: Ninety patients underwent axillary T2W-and GDF-MRI. Two radiologists independently scored each lymph node; first on T2W-MRI, subsequently adjusting their score on GDF-MRI. Diagnostic performance parameters were calculated on node-by-node and patient-by-patient validation with histopathology as the reference standard. Furthermore, learning curve analysis for reading GDF-MRI was performed. RESULTS: In patient-by-patient validation, overall reader performances for T2W-and GDF-MRI were similar with area under the receiver operating characteristic curves (AUC) of 0.75 and 0.77 (p = 0.731) for reader 1 and 0.79 and 0.72 (p = 0.156) for reader 2. For node-by-node validation, AUC values of T2W-and GDF-MRI were 0.76 and 0.82 (p = 0.018) and 0.77 and 0.77 (p = 0.998) for reader 1 and 2. The AUC for reader 1 was 0.71 for first one-third of nodes evaluated, improving to 0.80 and 0.95 for the next and last one-third, respectively. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) improved from 38%, 89%, 56%, and 79% to 60%, 93%, 64%, and 92%. The AUC of reader 2 improved from 0.69 to 0.79. CONCLUSION: The present study confirmed that GDF-MRI, in addition to T2W-MRI, has potential as a non-invasive method for nodal (re) staging in breast cancer. (C) 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

The ACOSOG-Z0011-study has resulted in a trend to a more conservative treatment of the axilla for selected sentinel-node-positive patients. However, axillary nodal involvement has always been an important factor for tumor staging and tailoring adjuvant chemotherapy plans. This study evaluates the impact of omitting completion axillary lymph node dissection (cALND) on the administration of adjuvant chemo (-immuno)therapy in Dutch clinical T1-2N0M0 (cT1-2N0M0) sentinel-node-positive breast cancer patients.Data were obtained from the nationwide NABON breast cancer audit. Descriptive analyses were used to demonstrate trends in axillary surgery and adjuvant chemo (-immuno)therapy. Multivariable logistic regression analyses were used to identify factors associated with the prescription of chemo (-immuno)therapy.In this cohort of 4331 patients, the omission of a cALND increased from 34% to 92%, and the administration of chemo (-immuno)therapy decreased from 68% to 55%, between 2011 and 2015 (P 0.001). Patients treated with cALND had an OR of 2.2 for receiving adjuvant chemo (-immuno)therapy compared with SLNB only patients. Lower age, a hormone receptor (HR) status other than HR-positive, HER2-negative, increasing tumor grade and stage, and a lymph node status ≥ pN2 were independently associated with a higher probability of chemo (-immuno)therapy (P 0.05).This study showed that Dutch cT1-2N0M0 sentinel node-positive breast cancer patients treated with cALND had a higher independent probability for receiving adjuvant chemo (-immuno)therapy compared with SLNB only patients, even when corrected for lymph node status and HR-status. Probably, the decisions to administer adjuvant chemo (-immuno)therapy were not only based on guidelines and tumor characteristics, but also on the preferences from physicians and patients.

Background Several trials are presently randomizing clinically node-negative breast cancer patients treated with breast-conserving therapy (BCT) to sentinel lymph node biopsy (SLNB) or watchful waiting. We aimed to investigate the elective radiation dose at the sentinel lymph node (SLN) site while evaluating two techniques for SLN localization, in breast cancer patients treated with lumpectomy and three-dimensional (3D) whole-breast radiotherapy. Methods The SLN site of consecutive Tis-2N0 breast cancer patients undergoing lumpectomy and forward intensity-modulated whole-breast radiotherapy was determined by the location of the hotspot on preoperative single-photon emission computed tomography (SPECT)/computed tomography (CT) and by a surgical clip placed at the removed SLN(s) during SLNB. The radiation dose at the SLN site was subsequently determined on the postoperative radiotherapy planning CT. An elective radiation dose to the SLN site was defined as at least 95 % of the breast dose. Results Of the 42 included patients, the mean percentage of the breast dose on the SLN site was 90 % (standard deviation 26, range 7–132, median 99), with a non-significant difference between the two techniques (surgical clip or SPECT/CT) (p = 0.608). In 32/42 patients (76 %) the SLN site received an elective radiation dose. Conclusions A surgical clip placed at the removed SLN(s) during SLNB proved to be an adequate method of determining the radiation dose at the SLN site when compared with using SPECT/CT. With the use of 3D radiotherapy, the site of the SLN is treated with an elective radiation dose in the majority of patients who are treated with BCT.

Purpose: To provide a systematic review and meta-analysis of studies investigating sentinel lymph node biopsy after neoadjuvant systemic therapy in pathologically confirmed node positive breast cancer patients.Methods: Pubmed and Embase databases were searched until June 19th, 2015. All abstracts were read and data extraction was performed by two independent readers. A random-effects model was used to pool the proportion for identification rate, false-negative rate (FNR) and axillary pCR with 95% confidence intervals. Subgroup analyses affirmed potential confounders for identification rate and FNR.Results: A total of 997 abstracts were identified and eventually eight studies were included. Pooled estimates were 92.3% (90.8-93.7%) for identification rate, 15.1% (12.7-17.6%) for FNR and 36.8% (34.2-39.5%) for axillary pCR. After subgroup analysis, FNR is significantly worse if one sentinel node was removed compared to two or more sentinel nodes (23.9% versus 10.4%, p = 0.026) and if studies contained clinically nodal stage 1-3, compared to studies with clinically nodal stage 1-2 patients (21.4 versus 13.1%, p = 0.049). Other factors, including single tracer mapping and the definition of axillary pCR, were not significantly different.Conclusion: Based on current evidence it seems not justified to omit further axillary treatment in every clinically node positive breast cancer patients with a negative sentinel lymph node biopsy after neoadjuvant systemic therapy. (C) 2015 Elsevier Ltd. All rights reserved.

Purpose To evaluate the diagnostic performance of unenhanced axillary T2-weighted and diffusion-weighted (DW) magnetic resonance (MR) imaging for axillary nodal staging in patients with newly diagnosed breast cancer, with node-by-node and patient-by-patient validation. Materials and Methods Institutional review board approval and informed consent were obtained. Fifty women (mean age, 60 years; range, 22-80 years) underwent high-spatial-resolution axillary 3.0-T T2-weighted imaging without fat suppression and DW imaging (b = 0, 500, and 800 sec/mm2), followed by either sentinel lymph node biopsy (SLNB) or axillary lymph node dissection. Two radiologists independently scored each lymph node on a confidence level scale from 0 (benign) to 4 (malignant), first on T2-weighted MR images, then on DW MR images. Two researchers independently measured the mean apparent diffusion coefficient (ADC) of each lymph node. Diagnostic performance parameters were calculated on the basis of node-by-node and patient-by-patient validation. Results With respective node-by-node and patient-by-patient validation, T2-weighted MR imaging had a specificity of 93%-97% and 87%-95%, sensitivity of 32%-55% and 50%-67%, negative predictive value (NPV) of 88%-91% and 86%-89%, positive predictive value (PPV) of 60%-70% and 62%-75%, and area under the receiver operating characteristic curve (AUC) of 0.78 and 0.80-0.88, with good interobserver agreement (kappa = 0.70). The addition of DW MR imaging resulted in lower specificity (59%-88% and 50%-84%), higher sensitivity (45%-64% and 75%-83%), comparable NPV (89% and 90%-91%), lower PPV (23%-42% and 34%-60%), and lower AUC (0.68-0.73 and 0.70-0.86). ADC measurement resulted in a specificity of 63%-64% and 61%-63%, sensitivity of 41% and 67%, NPV of 85% and 85%-86%, PPV of 18% and 35%-36%, and AUC of 0.54-0.58 and 0.69-0.74, respectively, with excellent interobserver agreement (intraclass correlation coefficient, 0.83). Conclusion Dedicated high-spatial-resolution axillary T2-weighted MR imaging showed good specificity on the basis of node-by-node and patient-by-patient validation, with good interobserver agreement. However, its NPV is still insufficient to substitute it for SLNB for exclusion of axillary lymph node metastasis. DW MR imaging and ADC measurement were of no added value. (c) RSNA, 2014.

During recent years, an increasing number of patients with ipsilateral breast tumor recurrence (IBTR) and previous axillary surgery have undergone repeat sentinel lymph node biopsy (rSLNB). The influence of axillary nodal status on prognosis for IBTR patients remains unclear. This study aimed to evaluate the technical success rate, follow-up assessment, and prognostic value of rSLNB for patients with IBTR. A systematic search conducted in MEDLINE, Embase, and the Cochrane Library up to July 2017 included all studies on rSLNB in IBTR. A total of 34 articles describing 1761 patients were identified. A repeat sentinel lymph node (rSLN) was successfully harvested from 64.3% of the patients with IBTR, and the rate was significantly higher for the patients who had a previous SLNB than for those who had a previous axillary lymph node dissection (ALND) (75.7% vs. 46.1%; P

To evaluate patterns of care in axillary surgery for Dutch clinical T1-4N0M0 (cT1-4N0M0) breast cancer patients and to assess the effect of the American College for Surgeons Oncology Group (ACOSOG)-Z0011 and After Mapping of the Axilla: Radiotherapy Or Surgery (AMAROS) trial on axillary surgery patterns in Dutch cT1-2N0M0 sentinel node positive breast cancer patients.Since publication of the ACOSOG-Z0011 and AMAROS trial, omitting a completion axillary lymph node dissection (cALND) in sentinel node positive breast cancer patients is proposed in selected patients.Data were obtained from the nationwide Nationaal Borstkanker Overleg Nederland breast cancer audit. Descriptive analyses were used to demonstrate trends in axillary surgery. Multivariable logistic regression analyses were used to identify factors associated with the omission of cALND in cT1-2N0M0 sentinel node-positive breast cancer patients.Between 2011 and 2015 in cT1-4N0M0 breast cancer patients, the use of sentinel lymph node biopsy as definitive axillary staging increased from 72% to 93%, and (c)ALND as definitive axillary staging decreased from 24% to 6% (P0.001). The use of cALND decreased from 75% to 17% in cT1-2N0 sentinel node-positive patients (P0.001). Earlier year of diagnosis, lower age, primary mastectomy, invasive lobular subtype, increasing tumor grade, and treatment in a nonteaching hospital were associated with a lower probability of omitting cALND (P0.001).This study shows a trend towards less extensive axillary surgery in Dutch cT1-T4N0M0 breast cancer patients; illustrated by an overall increase of sentinel lymph node biopsy and decrease in cALND. Despite this trend, particularly noticed in cT1-2N0 sentinel node-positive patients after publication of the ACOSOG-Z0011 and AMAROS trial, variations in patterns of care in axillary surgery are still present.

Background Between 20% and 42% of patients with clinically node-positive breast cancer achieve a pathologic complete response (pCR) of axillary lymph nodes after neoadjuvant chemotherapy or immunotherapy, or both, (chemo[immuno]therapy). Hypothetically, axillary lymph node dissection (ALND) may be safely omitted in these patients. This study aimed to develop a model for predicting axillary pCR in these patients. Patients and Methods We retrospectively identified patients with clinically node-positive breast cancer who were treated with neoadjuvant chemo(immuno)therapy and ALND between 2005 and 2012 in 5 hospitals. Patient and tumor characteristics, neoadjuvant chemo(immuno)therapy regimens, and pathology reports were extracted. Binary logistic regression analysis was used to predict axillary pCR with the following variables: age, tumor stage and type, hormone receptor and human epidermal growth factor receptor 2 (HER2) status, and administration of taxane and trastuzumab. The model was internally validated by bootstrap resampling. The overall performance of the model was assessed by the Brier score and the discriminative performance by receiver operating characteristic (ROC) curve analysis. Results A model was developed based on 291 patients and was internally validated with a scaled Brier score of 0.14. The area under the ROC curve of this model was 0.77 (95% confidence interval [CI], 0.71-0.82). At a cutoff value of predicted probability ≥ 0.50, the model demonstrated specificity of 88%, sensitivity of 43%, positive predictive value (PPV) of 65%, and negative predictive value (NPV) of 75%. Conclusion This prediction model shows reasonable accuracy for predicting axillary pCR. However, omitting axillary treatment based solely on the nomogram score is not justified. Further research is warranted to noninvasively identify patients with axillary pCR.

Background Results in breast cancer research are reported using study endpoints. Most are composite endpoints (such as locoregional recurrence), consisting of several components (for example local recurrence) that are in turn composed of specific events (such as skin recurrence). Inconsistent endpoint selection and definition might lead to unjustified conclusions when comparing study outcomes. This study aimed to determine which locoregional endpoints are used in breast cancer studies, and how these endpoints and their components are defined. Methods PubMed was searched for breast cancer studies published in nine leading journals in 2011. Articles using endpoints with a local or regional component were included and definitions were compared. Results Twenty-three different endpoints with a local or regional component were extracted from 44 articles. Most frequently used were disease-free survival (25 articles), recurrence-free survival (7), local control (4), locoregional recurrence-free survival (3) and event-free survival (3). Different endpoints were used for similar outcomes. Of 23 endpoints, five were not defined and 18 were defined only partially. Of these, 16 contained a local and 13 a regional component. Included events were not specified in 33 of 57 (local) and 27 of 50 (regional) cases. Definitions of local components inconsistently included carcinoma in situ and skin and chest wall recurrences. Regional components inconsistently included specific nodal sites and skin and chest wall recurrences. Conclusion Breast cancer studies use many different endpoints with a locoregional component. Definitions of endpoints and events are either not provided or vary between trials. To improve transparency, facilitate trial comparison and avoid unjustified conclusions, authors should report detailed definitions of all endpoints.

Objective To analyse bilateral differences in the cross-sectional area of the internal mammary artery (IMA) and vein (IMV) in breast cancer patients compared to healthy controls. Materials and methods On 135 breast MRIs the cross-sectional areas of the IMA and IMV were measured on the left and right side in the second and third intercostal space (ICS) by two independent readers. Differences were analysed using a linear mixed model. Results In the healthy control group (n = 91) no significant differences between the cross-sectional areas of the IMA and IMV were observed. Both readers reported a mean adjusted difference of 0.12 mm2 (p = 0.298) and 0.21 mm2 (p = 0.058) for the IMA in the second ICS. In the malignancy group (n = 44) the cross-sectional area was significantly larger on the malignancy side compared to the contralateral side. The largest difference in the IMA was measured in the second ICS with a mean adjusted difference for reader 1 of 1.37 mm2 (p < 0.001) and for reader 2 of 0.81 mm2 (p = 0.003). Conclusions The vascular cross-sectional area of internal mammary vessels was significantly different on the side with breast cancer compared to the contralateral side. This difference was not observed in healthy controls. Main messages MRI has become an important imaging modality in the diagnostic workup of breast cancer. In healthy persons no significant difference in the size of the left and right IMA is observed. A significant enlargement of the IMA on the malignant side occurs in most patients.

Objective To provide a systematic review of studies comparing the diagnostic performance of noninvasive techniques and axillary lymph node dissection in the identification of initially node positive patients with pathological complete response of axillary lymph nodes to neoadjuvant systemic therapy. Methods PubMed and Embase databases were searched until May 21st, 2014. First, duplicate studies were eliminated. Next, study abstracts were read by two readers to assess eligibility. Studies were selected based on predefined inclusion criteria. Of these, data extraction was performed by two readers independently. Results Of the 987 abstracts that were considered for inclusion, four were eligible for final analysis, which included a total of 572 patients. The diagnostic performance of clinical examination, axillary ultrasound, breast MRI, whole body 18 F-FDG PET-CT, and a prediction model to identify patients with pathological complete response were investigated. Studies were often limited by small sample size. Furthermore, systemic therapy regimens and definitions of clinical and pathological complete response were variable, refraining further pooling of data. The reported positive predictive value of different techniques to identify patients with axillary pathological complete response after neoadjuvant systemic therapy varied between 40% and 100%. Conclusion At present, there is no accurate noninvasive restaging technique able to identify patients with complete axillary response after neoadjuvant systemic therapy.

OBJECTIVES: To assess whether MRI can exclude axillary lymph node metastasis, potentially replacing sentinel lymph node biopsy (SLNB), and consequently eliminating the risk of SLNB-associated morbidity.METHODS: PubMed, Cochrane, Medline and Embase databases were searched for relevant publications up to July 2014. Studies were selected based on predefined inclusion and exclusion criteria and independently assessed by two reviewers using a standardised extraction form.RESULTS: Sixteen eligible studies were selected from 1,372 publications identified by the search. A dedicated axillary protocol [sensitivity 84.7 %, negative predictive value (NPV) 95.0 %] was superior to a standard protocol covering both the breast and axilla simultaneously (sensitivity 82.0 %, NPV 82.6 %). Dynamic, contrast-enhanced MRI had a lower median sensitivity (60.0 %) and NPV (80.0 %) compared to non-enhanced T1w/T2w sequences (88.4, 94.7 %), diffusion-weighted imaging (84.2, 90.6 %) and ultrasmall superparamagnetic iron oxide (USPIO)- enhanced T2*w sequences (83.0, 95.9 %). The most promising results seem to be achievable when using non-enhanced T1w/T2w and USPIO-enhanced T2*w sequences in combination with a dedicated axillary protocol (sensitivity 84.7 % and NPV 95.0 %).CONCLUSIONS: The diagnostic performance of some MRI protocols for excluding axillary lymph node metastases approaches the NPV needed to replace SLNB. However, current observations are based on studies with heterogeneous study designs and limited populations.MAIN MESSAGES: • Some axillary MRI protocols approach the NPV of an SLNB procedure. • Dedicated axillary MRI is more accurate than protocols also covering the breast. • T1w/T2w protocols combined with USPIO-enhanced sequences are the most promising sequences.

Several independent randomized controlled trials are initiated to investigate whether sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients with negative axillary ultrasound findings, who are treated with breast conserving therapy. A consequence of omitting sentinel lymph node biopsy is absence of pathological lymph node status information. We aimed to investigate the impact of omitting sentinel lymph node biopsy on adjuvant systemic treatment recommendations. Data from all consecutive patients with invasive breast cancer and negative axillary ultrasound findings treated with breast conserving therapy and sentinel lymph node biopsy between 2008 and 2012 were collected from a prospective database. Two methods, Adjuvant! Online and the Dutch breast cancer guideline 2012, were used to determine the adjuvant systemic treatment recommendations of every patient. At first, each patient was considered to be lymph node negative, and secondly the patients’ true pathological lymph node status was used. A total of 303 patients were consecutively included. Pathological lymph node status was pN0 in 72.3 %, pN0(i+) in 12.9 %, pN1mi+ in 5.6 %, pN1 in 7.3 %, and pN2 in 2.0 % of the patients. The decision to recommend adjuvant systemic treatment changed due to the pathological lymph node status in 1.0 % of the patients (3/303) when using Adjuvant! Online and in 3.6 % (11/303) when using the 2012 Dutch breast cancer guideline. The impact of the pathological lymph node status on adjuvant systemic treatment recommendations in clinically node negative breast cancer patients with negative axillary ultrasound findings treated with breast conserving therapy is limited. The safety of omitting the sentinel lymph node biopsy should be confirmed by the initiated randomized controlled trials.

Background: New insights show that an axillary lymph node dissection (ALND) may not always be indicated for metastases detected by ultrasound (pathologically proven). This study investigated whether axillary ultrasound accurately predicts pN0, pN1 and pN2-pN3 status. Methods: Data were retrospectively collected from all consecutive patients with invasive breast cancer who underwent (primary) surgery between 2008 and 2012. False negative percentages and negative predictive values (NPVs) for sonographic nodal staging were calculated for all patients and again for cT1 -2 patients treated by breast conserving therapy (BCT). Results: A total of 577 axillary ultrasounds were included. After negative ultrasound findings (cN0), pathology showed pN2-pN3 disease in 4.4% of these cases, with an NPV of 95.5% (93.4-97.1%). When cN1 (1-3 suspicious nodes) was predicted, pathology showed pN2-pN3 disease in 41.2%, with an NPV of 58.5% (44.2-71.5%). In the subgroup of patients with cT1-2 breast cancer that were treated by BCT, pathology showed pN2 -pN3 disease in 2.3% after negative ultrasound findings (cN0), with an NPV of 97.7% (94.9-99.0%). When cN1 was predicted (n = 12), pathology showed pN2-pN3 disease in 50.0%, with an NPV of 50.0% (22.3 -77.9%). A direct ALND was performed in these 12 cN1 cases; pathology showed six patients with pN1 (three patients with one and three with two macrometastases) and six with pN2-pN3 disease (4, 5, 11, 13, 16 or 22 macrometastases, respectively). Conclusion: In conclusion, a negative axillary ultrasound generally excludes the presence of pN2-pN3 disease. An axillary ultrasound cannot accurately differentiate between pN1 and pN2-pN3. It could be argued that the standard performance of an axillary ultrasound in breast cancer patients is questionable; multidisciplinary discussion could guide decisions on the use of axillary ultrasound for the individual patient.

OBJECTIVES: The objectives of this study were to evaluate whether the axillary lymph nodes show enhancement on magnetic resonance imaging (MRI) after gadofosveset administration, to assess the time to peak enhancement, and to determine the diagnostic performance of gadofosveset-enhanced MRI for axillary nodal staging. MATERIALS AND METHODS: Ten women whose conditions had been diagnosed with invasive breast cancer (>2 cm) underwent both nonenhanced and gadofosveset-enhanced 3-dimensional T1-weighted axillary MRI. Signal intensity of the axillary lymph nodes and different adjacent tissues was measured, and relative signal intensity (rSI) was calculated. A Wilcoxon signed rank test was used to compare results of rSI between different time intervals. A radiologist evaluated all lymph nodes with regard to size, morphologic features, and gadofosveset uptake. All MRI-depicted lymph nodes were matched with the lymph nodes that were removed during surgery. Nodal status was investigated by a pathologist. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of gadofosveset-enhanced MRI for axillary lymph node staging were calculated. RESULTS: After contrast administration, a significant signal increase was observed in the lymph nodes (P < 0.05). When compared with muscle or fat, rSI of the lymph nodes demonstrated a significant postcontrast peak enhancement between 11 minutes and 30 seconds and 20 minutes and 50 seconds (P < 0.05). A total of 152 lymph nodes were harvested during sentinel lymph node biopsy or axillary lymph node dissection, of which 116 were matched with the lymph nodes that were depicted on MRI. Histopathological examination resulted in 21 macrometastases and 8 micrometastases. Using contrast-enhanced MRI, 20 lymph nodes were rated as true positive; 83 as true negative; 4 as false positive; and 9 as false negative. This resulted in an overall node-by-node sensitivity, specificity, PPV, and NPV of 69%, 95%, 83%, and 90%, respectively. If the micrometastases were excluded from the analysis, MRI showed a sensitivity of 86% and a specificity of 94%. Calculated PPV and NPV were 75% and 97%, respectively. CONCLUSIONS: The axillary lymph nodes show enhancement on MRI after gadofosveset administration, with a peak enhancement between 11 minutes and 30 seconds and 20 minutes and 50 seconds. Diagnostic performance of gadofosveset-enhanced axillary lymph node imaging in patients with breast cancer is promising, but further studies need to confirm these results.

Summary Introduction: The rib-sparing technique to access the internal mammary vessels for microanastomosis is the current practice in our hospital nowadays. This study is performed to analyse the best intercostal space to expose those vessels. Patients and methods: Magnetic resonance imaging (MRI) of the chest wall of 133 women was evaluated. The Schwabegger classification (representing the anatomical variation), the intercostal space between ribs two, three and four, and the surface of the internal mammary artery and veins in the second and third intercostal space were determined on multiplanar reconstructed T2-weighted images. Results: In more than half of the cases, the anatomy followed Schwabegger variation two; one lateral artery and one medial vein were symmetrical. If a second vein was present, the bifurcation was most commonly in the third intercostal space. The second intercostal space above the mammary vessels was significantly wider than the third one. The surface of the artery and vein(s) was significantly larger in the second intercostal space. Conclusion: In most clinical situations, the second intercostal space is most likely the best approach to the internal mammary vessels for microanastomosis using a rib-sparing technique because of wider intercostal space and larger artery and vein. a 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by