Diagnostic imaging in lipedema: A systematic review.

BACKGROUND: Diagnosing lipedema remains a challenge due to its heterogeneous presentation, co-existing diseases, and the lack of objective diagnostic imaging. OBJECTIVE: This systematic review aims to outline the currently available diagnostic imaging methods to characterize lipedema in the legs along with their diagnostic performance. METHODS: PubMed, Embase, Google Scholar, Scopus, and Web of Science were searched. The quality assessment of diagnostic accuracy studies (QUADAS) tool was used for quality assessment. RESULTS: Thirty-two studies describing a total of 1154 patients with lipedema were included for final analysis. Features for lipedema have been defined using ultrasound (increased subcutaneous adipose tissue), lymphoscintigraphy (slowing of the lymphatic flow and a frequent asymmetry between the lower extremities), computed tomography (symmetrical bilateral soft tissue enlargement without either skin thickening or subcutaneous edema), magnetic resonance imaging (increased subcutaneous adipose tissue), MR lymphangiography (enlarged lymphatic vessels up to a diameter of 2 mm), and dual-energy X-ray absorptiometry (fat mass in the legs adjusted for body mass index (BMI) ≥ 0.46 or fat mass in the legs adjusted for total fat mass ≥ 0.384). CONCLUSION: The diagnostic performance of currently available imaging modalities for assessing lipedema is limited. Prospective studies are needed to evaluate and compare the diagnostic performance of each imaging modality. Imaging techniques focusing on the pathogenesis of the disease are needed.

Oncological Safety of Oncoplastic Level II Mammoplasties After Neoadjuvant Chemotherapy for Large Breast Cancers: A Matched-Cohort Analysis.

BACKGROUND: Oncoplastic surgery (OPS) has extended the indications for breast-conserving surgery (BCS). Its role in patients with large breast cancers treated with neoadjuvant chemotherapy (NAC) is unclear. This study evaluated the oncological safety of OPS for tumors with partial response after NAC. METHODS: A consecutive series of 65 patients who underwent OPS (study group) after NAC for large breast cancer from January 2004 to July 2018 was compared with 130 matched patients treated by NAC, followed by standard BCS in 65 cases and mastectomy in 65 cases (two case-controlled groups). RESULTS: The mean initial radiological tumor size was 46 mm. Residual pathological tumor size was 22 mm in the OPS cohort, 19 mm in the standard BCS cohort, and 31 mm in the mastectomy cohort (p > 0.05). The mean follow-up was 59 months in the study cohort. Five-year local recurrence rates were 0%, 0%, and 10.5% (0-22%) for the OPS, BCS, and mastectomy cohorts, respectively, while 5-year regional recurrence rates were 4.1% (0-11.1%), 0, and 19.4% (0-35.2%, p > 0.05), respectively. Five-year overall survival was 85.3% for the OPS cohort, 94.1% for the standard BCS cohort (p = 0.194), and 79.9% for the mastectomy cohort (p = 0.165). CONCLUSIONS: OPS is safe after NAC for large breast cancers, and provides excellent local control, identical to that of tumors with a better response, treated by standard BCS. After NAC, OPS can be a valuable treatment option for tumors that did not shrink optimally and would not be suitable for standard BCS.

Predicting the extent of nodal involvement for node positive breast cancer patients: Development and validation of a novel tool.

BACKGROUND: This study aimed to develop an easy to use prediction model to predict the risk of having a total of 1 to 2, ≥3, or ≥4 positive axillary lymph nodes (LNs), for patients with sentinel lymph node (SLN) positive breast cancer. METHODS: Data of 911 SLN positive breast cancer patients were used for model development. The model was validated externally in an independent population of 180 patients with SLN positive breast cancer. RESULTS: Final pathology after ALND showed additional positive LN for 259 (28%) of the patients. A total of 726 (81%) out of 911 patients had a total of 1 to 2 positive nodes, whereas 175 (19%) had ≥3 positive LNs. The model included three predictors: the tumor size (in mm), the presence of a negative SLN, and the size of the SLN metastases (in mm). At external validation, the model showed a good discriminative ability (area under the curve = 0.82; 95% confidence interval = 0.74-0.90) and good calibration over the full range of predicted probabilities. CONCLUSION: This new and validated model predicts the extent of nodal involvement in node-positive breast cancer and will be useful for counseling patients regarding their personalized axillary treatment.

Patient Selection for Clinical Trials Eliminating Surgery for HER2-Positive Breast Cancer Treated with Neoadjuvant Systemic Therapy.

BACKGROUND: Patients with epidermal growth factor receptor 2-positive (HER2+) breast cancer and pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) may be candidates for nonoperative clinical trials if residual invasive and in situ disease are eradicated. METHODS: This study analyzed 280 patients with clinical T1-2N0-1 HER2+ breast cancer who underwent NST followed by surgical resection to determine key characteristics of patients with pCR in the breast and lymph nodes compared with those with residual disease. RESULTS: Of the 280 patients, 102 (36.4%) had pCR in the breast and lymph nodes after NST, and 50 patients (17.9%) had residual ductal carcinoma in situ (DCIS) in the breast only. For 129 patients (46.1%), DCIS was present on the pretreatment biopsy, and NST failed to eradicate the DCIS component in 64.3%. Patients with residual disease were more likely to have hormone receptor-positive (HR+) tumors than those with negative tumors (73.4% vs. 50.8%; p < 0.0001). Radiologic response (odds ratio [OR], 5.62; p = 0.002) and HR+ status (OR, 2.56; p < 0.0001) were predictive of residual disease. Combined imaging methods after NST had a sensitivity of 97.1% and a negative predictive value of 70.6% for detection of residual disease. Patients with invasive disease and DCIS shown on the pretreatment core biopsy were less likely than those without DCIS to achieve pCR in the breast (31% vs. 43%; p = 0.038). CONCLUSION: The study results delineate and identify unique characteristics associated with HER2+ breast cancers that are important in selecting patients for inclusion in clinical trials assessing nonoperative management after NST, and the low negative predictive value of imaging mandates image-guided biopsy for selection.

Incidence and Outcome of Breast Biopsy Procedures During Follow-up After Treatment for Breast Cancer.

Importance: No comprehensive data are available regarding the frequency of breast biopsies performed during follow-up of treatment for invasive breast cancer. Objective: To determine how often patients treated for breast cancer require breast biopsies during follow-up. Design, Setting, and Participants: This nationwide population-based cohort study included 41 510 patients 64 years or younger in a commercial insurance database and 80 369 patients 66 years or older in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were diagnosed with incident invasive breast cancer (stages I-III) from January 1, 2000, through December 31, 2011. Diagnosis and procedural codes were used to identify biopsy rates during follow-up. Data were analyzed from March 3 through October 3, 2017. Main Outcomes and Measures: Cumulative incidence and adjusted risk of breast biopsy and subsequent breast cancer treatment were calculated using the Kaplan-Meier method and Cox proportional hazards regression. All statistical tests were 2 sided. Results: Among the 121 879 patients in the study population, 5- and 10-year overall incidences of breast biopsy were 14.7% and 23.4%, respectively, in the commercial insurance cohort and 11.8% and 14.9%, respectively, in the SEER-Medicare cohort. The 5-year estimated incidence of breast biopsy was higher among women treated with brachytherapy (24.0% in the commercial insurance and 25.0% in the SEER-Medicare cohorts) than among those treated with whole-breast irradiation (16.7% in the commercial insurance and 15.1% in the SEER-Medicare cohorts) and persisted after multivariate adjustment in the commercial insurance (hazard ratio [HR], 1.53; 95% CI, 1.38-1.70; P < .001) and SEER-Medicare (HR, 1.76; 95% CI, 1.63-1.91; P < .001) cohorts. Adjuvant chemotherapy use (HR, 1.31; 95% CI, 1.25-1.37; P < .001) and patient age (>85 vs 66-69 years; HR, 0.40; 95% CI, 0.36-0.44; P < .001) in the SEER-Medicare cohort and endocrine therapy in the commercial insurance (HR, 0.88; 95% CI, 0.82-0.93; P < .001) and SEER-Medicare (HR, 0.91; 95% CI, 0.85-0.97; P = .002) cohorts were independently associated with biopsy. After unilateral mastectomy, the estimated 5-year contralateral breast biopsy rates were 10.4% and 7.7% in the commercial insurance and SEER-Medicare cohorts, respectively. Of the patients with breast biopsy, 1239 of 4158 patients (29.8%) in the commercial insurance cohort and 2258 of 9747 patients (23.2%) in the SEER-Medicare cohort underwent subsequent cancer treatment. Conclusions and Relevance: These data on the need for breast biopsies during follow-up and subsequent treatments from a large cohort of women with commercial insurance and Medicare can be used in the context of therapy-planning discussions and survivorship expectations for patients with breast cancer.

Long-term Results After Oncoplastic Surgery for Breast Cancer: A 10-year Follow-up.

OBJECTIVE: The aim of this study was to evaluate the long-term oncologic outcome after oncoplastic surgery (OPS). BACKGROUND: OPS combines wide tumor excision with reduction mammoplasty techniques thus extending breast conserving surgery to large tumors that might else be proposed a mastectomy. Little data are available about the oncologic results for breast conserving surgery of these larger tumors. METHODS: From January 2004 until March 2016, a total of 350 oncoplastic breast reductions were prospectively entered into a database. Patients were included if their breast reshaping included a reduction mammoplasty with skin excision (Level 2 oncoplastic techniques). RESULTS: Histologic subtypes were: invasive ductal carcinoma in 219 cases (62.6%), ductal carcinoma in situ (DCIS) in 88 cases (25.1%), and invasive lobular carcinoma in 43 (12.3%) cases. Seventy-three of the invasive cancers (27.9%) received neoadjuvant chemotherapy. The mean resection weight was 177 grams. The mean pathological tumor size was 26 mm (range 0-180 mm) and varied from 23 mm (4-180 mm) for invasive cancers to 32 mm (0-100 mm) for DCIS. Specimen margins were involved in 12.6% of the cases; 10.5% of invasive ductal, 14.7% of DCIS, and 20.9% of invasive lobular. The overall breast conservation rate was 92% and varied from 87.4% for DCIS to 93.5% for the invasive cancers. Thirty-one patients (8.9%) developed one or more postoperative complications, inducing a delay in postoperative treatments in 4.6% of patients. The median follow up was 55 months. The cumulative 5-year incidences for local, regional, and distant recurrences were 2.2%, 1.1%, and 12.4%, respectively. CONCLUSIONS: Oncoplastic breast reductions allow wide resections with free margins and can be used for large cancers as an alternative to mastectomy.

Multimodality Imaging for Evaluating Response to Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: Neoadjuvant chemotherapy is becoming the standard of care for patients with locally advanced breast cancer. Conventional imaging modalities used for the assessment of tumor response to neoadjuvant chemotherapy rely on changes in size or morphologic characteristics and, therefore, are inherently limited. CONCLUSION: Functional imaging technologies evaluate vascular, metabolic, biochemical, and molecular changes in cancer cells and have a unique ability to detect specific biologic tumor markers, assess therapeutic targets, predict early response to neoadjuvant chemotherapy, and guide individualized cancer therapy.

Breast Cancer Clinical Trials: Past Half Century Moving Forward Advancing Patient Outcomes.

Clinical trials in breast cancer have contributed immensely to the advancements of modern multimodal breast cancer treatment. Due to improved screening methods and more effective biologic-based tailored systemic therapies, the extent of surgery necessary for local and systemic control of disease is decreasing. Sequential trials for ductal carcinoma in situ (DCIS) have changed the management of this disease and are culminating in randomized active surveillance studies in an effort potentially to prevent overtreatment of low- and intermediate-grade disease. For patients with initial node-positive disease, clipping and marking of the biopsy-proven nodal metastases before the start of neoadjuvant chemotherapy can allow for selective node dissection based on the axillary response. With the current advances in primary systemic therapy, feasibility trials are beginning to investigate the potential of nonoperative therapy for invasive cancers with percutaneously documented pathologic complete response. This article presents a review and update on landmark clinical trials related to DCIS, the extent of axillary surgery in node-positive disease, and the integration of systemic therapy with local therapy.

Selective elimination of breast cancer surgery in exceptional responders: historical perspective and current trials.

With improvements in chemotherapy regimens, targeted therapies, and our fundamental understanding of the relationship of tumor subtype and pathologic complete response (pCR), there has been dramatic improvement in pCR rates in the past decade, especially among triple-negative and human epidermal growth factor receptor 2-positive breast cancers. Rates of pCR in these groups of patients can be in the 60 % range and thus question the paradigm for the necessity of breast and nodal surgery in all cases, particularly when the patient will be receiving adjuvant local therapy with radiotherapy. Current practice for patients who respond well to neoadjuvant chemotherapy (NCT) is often to proceed with the same breast and axillary procedures as would have been offered women who had not received NCT, regardless of the apparent clinical response. Given these high response rates in defined subgroups among exceptional responders it is appropriate to question whether surgery is now a redundant procedure in their overall management. Further, definitive radiation without surgical resection with or without systemic therapy has been proven effective for several other malignant disease sites including some stages of esophageal, anal, laryngeal, prostate, cervical, and lung carcinoma. The main impediments for potential elimination of surgery have been the fact that prior and current standard and functional breast imaging methods are incapable of accurate prediction of residual disease and that integrating percutaneous biopsy of the breast primary and nodes following NCT may circumvent this issue. This article highlights historical attempts at omission of surgery following NCT in an earlier era, the current status of breast and nodal imaging to predict residual carcinoma, and ongoing and planned trials designed to identify appropriate patients who might be selected for clinical trials designed to test the safety of selected elimination of breast cancer surgery in percutaneous image-guided biopsy-proven exceptional responders to NCT.

Is SLN Biopsy Alone Safe in SLN Positive Breast Cancer Patients?

The Z0011 trial demonstrated no difference in overall survival (OS) and locoregional recurrence in breast cancer patients with a positive sentinel lymph node (SLN) randomized to axillary lymph node dissection (ALND) or no further surgery. The aim of this study was to evaluate locoregional recurrence in a nonrandomized group of SLN positive patients, in whom cALND was not performed, that were retrospectively categorized by the Z0011 eligibility criteria. From two hospital breast cancer databases consisting of 656 consecutive SLN positive breast cancer patients, 88 patients, who did not undergo cALND, were identified. This population was categorized by the Z0011 inclusion criteria (e.g., eligible versus ineligible) and the groups were compared. Thirty-four patients (38.6%) were retrospectively eligible for omitting cALND according to the Z0011 criteria and 54 (61.4%) were not. The median number of SLNs removed in both groups was 1 (range 1-5). The number of positive SLNs did not differ between the groups. Tumor size was slightly larger in the ineligible group (21 mm versus 19 mm) and 76% of patients in the ineligible group underwent a mastectomy. At a median follow-up of 26 months (range 1-84 months), one axillary recurrence was observed in the ineligible group versus 0 in the eligible group. Axillary recurrence was low, even in patients who did not meet the Z0011 inclusion criteria. Future trials that randomize Z0011 ineligible patients are needed to investigate long-term results.

A simple risk score to predict the presence of non-sentinel lymph node metastases in breast cancer patients with a positive sentinel node.

BACKGROUND: Historically, completion axillary lymph node dissection (cALND) is recommended in sentinel lymph node (SLN)-positive patients. However, the high rate of negative non-sentinel nodes (NSNs) in cALND and the reported low axillary recurrence rates have led to a more conservative approach. A risk score was developed to identify a patient's individual risk for NSN metastases. METHODS: Data of 182 SLN-positive patients who underwent cALND were used for risk score development. The risk score, consisting of pathological tumor size (≤ 20/>20 mm), lymphovascular invasion (no/yes), extracapsular extension (no/yes), size of metastases (≤ 2/>2 mm), and number of positive SLNs (1/>1), was subsequently validated on an external population (n = 180). RESULTS: The area under the receiver operating characteristic curve was 0.78 (95 % CI 0.71-0.85) in the original population and 0.78 (95 % CI 0.70-0.85) in the validation population. Based on the predicted risk for positive NSNs, three groups were defined: low risk (≤ 20 %), intermediate risk (21-50 %), and high risk (>50 %). In total, 88 patients met the Z0011 inclusion criteria and none of them had a high predicted risk. Of the 199 non-Z0011 patients, 67 (33.7 %) had low risk, 96 (48.2 %) had intermediate risk, and 36 (18.1 %) had high risk. CONCLUSION: A simple risk score, integrating just five clinicopathological variables, was developed that may assist in individual decision making regarding ALND in SLN-positive patients outside of the Z0011 trial.

Progressive respiratory distress due to neck mass.

The present report describes the case of an 80-year-old woman who presented at the emergency department with progressive respiratory distress caused by a massive anterior neck mass with tracheal deviation and compression. A CT scan showed diffuse enlargement of the thyroid gland. The patient underwent a left-sided hemithyroidectomy. Pathology unexpectedly revealed a primary thyroid lymphoma. Treatment with prednisone and vincristine was initiated to reduce tumour size and preserve the airway, resulting in rapid volume reduction and airway expansion. Primary thyroid lymphoma is a rare entity that requires adequate diagnosis and rapid initiation of treatment to reduce tumour volume and to prevent airway compromise.