Lipedema: What we don't know.

BACKGROUND: Lipedema is a loose connective tissue disease characterized by a disproportionate accumulation of adipose tissue in the limbs of women. Despite its incidence of 10-20%, lipedema is often underdiagnosed and misdiagnosed. OBJECTIVES: This review aims to outline current, available evidence regarding this enigmatic syndrome and gives a synopsis of the subjects that are still unknown. MATERIALS AND METHODS: PubMed and Embase searches were conducted to identify relevant articles on lipedema pathophysiology, clinical presentation, diagnosis, and treatment. RESULTS: Lipedema can be considered a disease of the adipocytes or a circulatory disorder of the lymphatics. The relationship between lymphatics and adipose tissue remains controversial. The clinical distinction between lipedema, lymphedema, phlebolymphedema, and lipolymphedema can be difficult. Diagnoses often coexist, further complicating the diagnosis of lipedema, which is currently made on clinical grounds alone. The value of diagnostic imaging studies is unclear. Liposuction appears to be an effective treatment and significantly improves symptoms. CONCLUSION: Diagnosing lipedema remains a challenge due to its heterogeneous presentation, co-existing diseases, and lack of objective diagnostic imaging. Further directions for research include the effect of excess skin resection surgery on lymphatic drainage.

Oncoplastic Level 2 Mammoplasty for Large DCIS: 5-Year Results.

BACKGROUND: Oncoplastic surgery (OPS) allows wider resections with immediate breast reshaping by mammoplasty. This study reviews our experience with level 2 mammoplasties in patients with histology-proven pure ductal carcinoma in situ (DCIS). METHOD: From a prospectively maintained database of 392 consecutive oncoplastic level 2 mammoplasties, 68 patients presented with pure DCIS. Involved margin rates and locoregional recurrence rates were calculated, with 76 months (0-166 months) median follow-up. RESULTS: The mean pathological tumor size was 34 mm (median 26 mm, range 2-106 mm). The mean resection weight was 191 g (median 131 g, range 40-1150 g). Margins were clear in 58 cases (85.3%) and involved in 10 cases (14.7%). Margins were involved in 1 out of 54 (1.9%) cases with tumor size under 50 mm and in 9 out of 14 (64.3%) cases with tumor size higher than 50 mm (p < 0.001). On multivariable analysis, only tumor size > 50 mm [odds ratio (OR) 95.400; p < 0.001] was independently associated with involved margins. Seven patients had mastectomy. The overall breast conservation rate was 89.4%, and 100% for tumors less than 5 cm. There were three local recurrences. The 5-year cumulative incidence for local recurrence was 5.5% (0-11.5%). CONCLUSIONS: OPS is a safe solution for large DCIS up to 50 mm, with an involved margin rate of only 1.9%, and can thus reduce the mastectomy rate in this group. As margin involvement significantly increases for tumors larger than 5 cm, better preoperative localization and/or wider excisions are necessary in this group.

Baseline factors predicting a response to neoadjuvant chemotherapy with implications for non-surgical management of triple-negative breast cancer.

BACKGROUND: Patients with triple-negative breast cancer (TNBC) and a pathological complete response (pCR) after neoadjuvant chemotherapy may be suitable for non-surgical management. The goal of this study was to identify baseline clinicopathological variables that are associated with residual disease, and to evaluate the effect of neoadjuvant chemotherapy on both the invasive and ductal carcinoma in situ (DCIS) components in TNBC. METHODS: Patients with TNBC treated with neoadjuvant chemotherapy followed by surgical resection were identified. Patients with a pCR were compared with those who had residual disease in the breast and/or lymph nodes. Clinicopathological variables were analysed to determine their association with residual disease. RESULTS: Of the 328 patients, 36·9 per cent had no residual disease and 9·1 per cent had residual DCIS only. Patients with residual disease were more likely to have malignant microcalcifications (P = 0·023) and DCIS on the initial core needle biopsy (CNB) (P = 0·030). Variables independently associated with residual disease included: DCIS on CNB (odds ratio (OR) 2·46; P = 0·022), T2 disease (OR 2·40; P = 0·029), N1 status (OR 2·03; P = 0·030) and low Ki-67 (OR 2·41; P = 0·083). Imaging after neoadjuvant chemotherapy had an accuracy of 71·7 (95 per cent c.i. 66·3 to 76·6) per cent and a negative predictive value of 76·9 (60·7 to 88·9) per cent for identifying residual disease in the breast and lymph nodes. Neoadjuvant chemotherapy did not eradicate the DCIS component in 55 per cent of patients. CONCLUSION: The presence of microcalcifications on imaging and DCIS on initial CNB are associated with residual disease after neoadjuvant chemotherapy in TNBC. These variables can aid in identifying patients with TNBC suitable for inclusion in trials evaluating non-surgical management after neoadjuvant chemotherapy.

Breast conserving surgery for extensive DCIS using multiple radioactive seeds.

BACKGROUND AND OBJECTIVES: Breast conserving surgery (BCS) can be challenging for large regions of ductal carcinoma in situ (DCIS), resulting in high rates of positive resection margins. Radioactive seed localization (RSL) using multiple radioactive iodine (125I) seeds can be used to bracket extensive DCIS (eDCIS). The goal of this study was to retrospectively compare the use of a single or multiple 125I seeds in RSL to enable BCS in patients with eDCIS. METHODS: All patients with eDCIS (area of ≥3.0 cm) who underwent either single or multiple-seed RSL between January 2008 and December 2016 were included. Patient, tumor and surgery characteristics were compared between both groups. Primary outcome measures were positive resection margin and re-operation rates. RESULTS: Respectively 48 and 58 patients with eDCIS underwent single- and multiple-seed RSL and subsequent BCS. The rate of positive resection margin (focal and more than focal) with single-seed RSL was 47.9%, compared to 29.3% with multiple-seed RSL (p = 0.06). The re-operation rate was 39.6% with single-seed RSL and 20.7% in the multiple-seed RSL group (p = 0.05). CONCLUSION: Multiple-seed RSL enables bracketing of large areas of DCIS, with the potential to decrease the high rate of positive resection margins in this patient group.

A prospective randomized study comparing centrifugation and sedimentation for fat grafting in breast reconstruction.

BACKGROUND: Fat grafting is an efficient method to correct large volumetric defects after mastectomy. There is an ongoing debate regarding the best method of processing the harvested fat before fat grafting. This study aimed to introduce a new MRI model and to compare two fat processing techniques measuring the gain in soft tissue thickness after fat grafting to the chest wall. METHODS: Fifty-one mastectomy patients (one double sided), who required delayed implant reconstruction, with poor skin conditions were proposed fat grafting prior to implant reconstruction. At the time of fat grafting, patients were randomly assigned to centrifugation or sedimentation of the aspirated fat. The trial was undertaken in a single-center private practice setting. The gain in soft tissue thickness of the chest wall was measured using an MRI model, with 12 predefined points for measurement. Two MRIs were performed, one prior to fat grafting and one 8 weeks thereafter. The radiologist was blinded to the fat graft processing method used. RESULTS: Seven cases were excluded because they did not complete their second MRI. The analyses were thus based on 44 patients (one double sided). Centrifugation was performed in 21 cases and sedimentation in 24 cases. The mean gain in soft tissue thickness was +7.0 mm in the centrifugation group and +8.8 mm in the sedimentation group (p = .268). The mean operative time was 88 min in the centrifugation group and 78 min in the sedimentation group (p = .11). There were no adverse events for any of the patients. CONCLUSIONS: We developed a simple and reproducible MRI model to objectively measure and evaluate different fat processing techniques prior to fat grafting. At a median time of 8 weeks after one session of fat grafting, there was no benefit of centrifugation over sedimentation.

A prospective validation study of sentinel lymph node biopsy in multicentric breast cancer: SMMaC trial.

BACKGROUND: Multicentric breast cancer is often considered a contra-indication for sentinel lymph node (SLN) biopsy due to concerns with sensitivity and false negative rate. To assess SLN feasibility and accuracy in multicentric breast cancer, the multi-institutional SMMaC trial was conducted. METHODS: In this study 30 patients with multicentric breast cancer and a clinically negative axilla were prospectively included. Periareolar injection of radioisotope and blue dye was administered. In all patients SLN biopsy was validated by back-up completion axillary lymph node dissection. RESULTS: the SLN was successfully identified in 30 of 30 patients (identification rate 100%). The incidence of axillary metastases was 66.7% (20/30). The false negative rate was 0% (0/20) and the sensitivity was 100% (20/20). The negative predictive value was 100% (10/10). CONCLUSION: SLN biopsy in multicentric breast cancer seems feasible and accurate and should therefore be considered in patients with multicentric breast cancer and clinically negative axilla.

Discordance between number of scintigraphic and perioperatively identified sentinel lymph nodes and axillary tumour recurrence.

BACKGROUND: In breast cancer, sentinel node biopsy is considered the standard method to assess the lymph node status of the axilla. Preoperative identification of sentinel lymph nodes (SLN) is performed by injecting a radioactive tracer, followed by lymphoscintigraphy. In some patients there is a discrepancy between the number of lymphoscintigraphically identified sentinel nodes and the number of nodes found during surgery. We hypothesized that the inability to find peroperatively all the lymphoscintigraphically identified sentinel nodes, might lead to an increase in axillary recurrence because of positive SLNs not being removed. METHODS: Patients who underwent sentinel node biopsy between January 2000 and July 2010 were identified from a prospectively collected database. The number of lymphoscintigraphically and peroperatively identified sentinel nodes were reviewed and compared. Axillary recurrences were scored. RESULTS: 1368 patients underwent a SLN biopsy. Median follow up was 58.5 months (range 12-157). Patient and tumour characteristics showed no significant differences. In 139 patients (10.2%) the number of radioactive nodes found during surgery was less than preoperative scanning (group 1) and in 89.8% (N = 1229) there were equal or more peroperative nodes identified than seen lymphoscintigraphically (group 2). In group 1, 0/139 patients (0%) developed an axillary recurrence and in the second group this was 25/1229 (2.0%) respectively. No significant difference between groups regarding axillary recurrence, sentinel node status and distant metastasis was found. CONCLUSION: Axillary recurrence rate is not influenced by the inability to remove all sentinel nodes during surgery that have been identified preoperatively by scintigraphy.

Evaluation of the benefit of routine intraoperative frozen section analysis of sentinel lymph nodes in breast cancer.

Aims. Intraoperative analysis of the sentinel lymph node (SLN) by frozen section (FS) allows for immediate axillary lymph node dissection (ALND) in case of metastatic disease in patients with breast cancer. The aim of this study is to evaluate the benefit of intraoperative FS, with regard to false negative rate (FNR) and influence on operation time. Materials and Methods. Intraoperative analysis of the SLN by FS was performed on 628 patients between January 2005 and October 2009. Patients were retrospectively studied. Results. FS accurately predicted axillary status in 525 patients (83.6%). There were 78 true positive findings (12.4%), of which there are 66 macrometastases (84.6%), 2 false positive findings (0.3%), and 101 false negative findings (16.1%), of which there are 65 micrometastases and isolated tumour cells (64.4%) resulting in an FNR of 56.4%. Additional operation time of a secondary ALND after wide local excision and SLNB is 17 minutes, in case of ablative surgery 35 minutes. The SLN was negative in 449 patients (71.5%), making their scheduled operation time unnecessary. Conclusions. FS was associated with a high false negative rate (FNR) in our population, and the use of telepathology caused an increase in this rate. Only 12.4% of the patients benefited from intraoperative FS, as secondary ALND could be avoided, so FS may be indicated for a selected group of patients.

Assessment of the Memorial Sloan-Kettering Cancer Center nomogram to predict sentinel lymph node metastases in a Dutch breast cancer population.

AIM: Sentinel lymph node (SLN) biopsy is an accepted alternative to axillary lymph node dissection to assess the axillary tumour status in breast cancer patients. Memorial Sloan-Kettering Cancer Center (MSKCC) developed a nomogram to predict the likelihood of SLN metastases in breast cancer patients. Nomogram performance was tested on a Dutch population. METHODS: Data of 770 breast cancer patients who underwent successful SLN biopsy were collected. SLN metastases were present in 222 patients. A receiver operating characteristic (ROC) curve was drawn and the area under the curve was calculated to assess the discriminative ability of the MSKCC nomogram. A calibration plot was drawn to compare actual versus nomogram-predicted probabilities. RESULTS: The area under the ROC curve for the predictive nomogram was 0.67 (95% confidence interval 0.63-0.72) as compared to 0.75 in the original population. The nomogram was well-calibrated in the Dutch population. CONCLUSIONS: In a Dutch population, the MSKCC nomogram estimated risk of sentinel node metastases in breast cancer patients well (i.e. calibration) with reasonable discrimination (area under ROC curve). Nomogram performance on core needle biopsy data has to be evaluated prospectively.

Meta-analysis of predictive factors for non-sentinel lymph node metastases in breast cancer patients with a positive SLN.

AIMS: A meta-analysis was performed to identify the clinicopathological variables most predictive of non-sentinel node (NSN) metastases when the sentinel node is positive. METHODS: A Medline search was conducted that ultimately identified 56 candidate studies. Original data were abstracted from each study and used to calculate odds ratios. The random-effects model was used to combine odds ratios to determine the strength of the associations. FINDINGS: The 8 individual characteristics found to be significantly associated with the highest likelihood (odds ratio >2) of NSN metastases are SLN metastases >2mm in size, extracapsular extension in the SLN, >1 positive SLN, ≤1 negative SLN, tumour size >2cm, ratio of positive sentinel nodes >50% and lymphovascular invasion in the primary tumour. The histological method of detection, which is associated with the size of metastases, had a correspondingly high odds ratio. CONCLUSIONS: We identified 8 factors predictive of NSN metastases that should be recorded and evaluated routinely in SLN databases. These factors should be included in a predictive model that is generally applicable among different populations.

Validation of a nomogram to predict the risk of nonsentinel lymph node metastases in breast cancer patients with a positive sentinel node biopsy: validation of the MSKCC breast nomogram.

BACKGROUND: Completion axillary lymph node dissection (ALND) remains the standard of care for patients with disease-positive sentinel lymph nodes (SLN). However, approximately two-thirds will have no additional disease-positive nodes. To identify the patient's individual risk for non-SLN metastases, the Memorial Sloan-Kettering Cancer Center (MSKCC) developed a nomogram. METHODS: The records of 182 breast cancer patients who underwent SLN and ALND were selected. Serial hematoxylin and eosin (HE) analysis and immunohistochemistry were routinely performed on each sentinel node. For application of the nomogram, the detection method was assigned in two ways: for all metastases visible by serial HE, the method of detection was scored as "serial HE" (method 1), independent of the tumor size, and by a combination of size and staining method (method 2); so macrometastasis were scored as detected by routine HE, micrometastasis by serial HE, and isolated tumor cells by immunohistochemistry. A receiver operating characteristic curve (ROC) was drawn, and the area under the curve was calculated to assess the discriminative power of the nomogram. RESULTS: The area under the ROC was .71 (range, .64-.79) according to method 1 and .75 (range, .67-.88) according to method 2. CONCLUSIONS: Because the variable "method of detection" in the MSKCC nomogram is a surrogate for SLN metastasis size, the size category of the SLN metastasis can be used in applying the nomogram to patients in whom the SLN histologic analysis is performed by a much different procedure than that used to develop the MSKCC nomogram. This results in an improved predictive accuracy.

The value of sentinel lymph node biopsy in ductal carcinoma in situ (DCIS) and DCIS with microinvasion of the breast.

AIM: Ductal carcinoma in situ (DCIS) refers to the preinvasive stage of breast carcinoma and should not give axillary metastases. Its diagnosis, however, is subject to sampling errors. The role of sentinel lymph node biopsy (SLNB) in management of DCIS or DCISM (with microinvasion) remains unclear. The purpose of this study was to review our experience with SLNB in DCIS and DCISM. METHODS: A review of 51 patients with a diagnosis of DCIS (n=45) or DCISM (n=6), who underwent SLNB and a definitive breast operation between January 1999 and December 2006, was performed. RESULTS: In 10 patients (19.6%) definitive histology revealed an invasive carcinoma. SLN (micro)metastases were detected in 5 out of 51 patients, of whom 2 had a preoperative diagnosis of grade III DCIS and 3 of DCISM. Three patients (75%) had micrometastases (< 2 mm) only. In 2 patients, histopathology demonstrated a macrometastasis (> 2 mm). All 5 patients underwent axillary dissection. No additional positive axillary lymph nodes were found. CONCLUSIONS: In case of a preoperative diagnosis of grade III DCIS or a grade II DCIS with comedo necrosis and DCIS with microinvasion, an SLNB procedure has to be considered because in almost 20% of the patients an invasive carcinoma is found after surgery. In this case the SLNB procedure becomes less reliable after a lumpectomy or ablation has been performed. SLN (micro)metastases were detected in nearly 10% of the patients. The prognostic significance of individual tumour cells remains unclear.

The prognostic value of abnormal findings on radiographic swallowing studies after total laryngectomy.

Pharyngocutaneous fistulae are a common complication after total laryngectomy. Our study evaluates the correlation of postoperative radiographic swallowing studies and clinical symptoms. We also propose a grading system to classify leaks radiographically. The records of 45 patients who underwent total laryngectomy were retrospectively reviewed. All patients had a radiographic swallowing study (RSS) on or around the tenth postoperative day. A grading system was developed to classify radiographic findings (grade 0-5). Twenty-two patients had an abnormal RSS (grade 2-5). Three patients (13.6%) had clinical signs of impending fistula whereas radiography showed moderate leakage (grade 3) in one patient and a pharyngocutaneous fistula (grade 5) in two. The other 19 patients with radiographically demonstrated leakage had no clinical signs of anastomotic complications. After total laryngectomy, radiography may reveal anastomotic complications of varying severity. The grading system used in this study enabled us to objectively classify the radiological abnormalities on swallowing studies. Because most radiographic leakages were clinically silent and not all clinically apparent fistula were radiographically visible in our study, the role of routine postoperative radiographic swallowing studies in the absence of clinical signs or fistula remains unclear.