Hygroscopic sonographically detectable clips form characteristic breast and lymph node pseudocysts.

The use of hygroscopic sonographically detectable clips (HSDCs) has dramatically increased during the last years, especially in breast cancer patients who undergo neoadjuvant chemotherapy. The aims of this study are to define the appearance of HSDC sites in histopathological specimens, and to enable pathologists to recognize these sites and differentiate them from other lesions. We examined 124 breast cancer specimens in which the application of HSDCs was documented, 88 breast tissues and 36 lymph nodes, and analyzed the appearance of the clip site in these tissues. The clip site was clearly detected histologically in 79/88 (90%) of the breast specimens and in 29/36 (81%) of lymph node specimens. In most of the specimens, the HSDC site had a specific characteristic appearance of a pseudocyst, lined by layers of epithelioid histiocytes, sometimes with pseudopapillary formation, and with minimal or no fibrosis. This was the appearance in 69 of the breast specimens and in 23 of the lymph node specimens. In other specimens, scarring, scattered foamy macrophages and abundant siderophages were the predominant findings, as usually found in sites of other clips. As non-palpable breast lesions become more frequent, clips play a major role in the treatment of breast cancer, making them an important component of the communication among radiologists, surgeons, pathologists, and oncologists. HSDCs in tissues have a characteristic appearance with an epithelioid component. Pathologists should be able to recognize this finding, differentiate it from other breast lesions and include it in the pathology report.

Detectability of Hygroscopic Clips Used in Breast Cancer Surgery.

Sonographically detectable clips were introduced over the last decade. We retrospectively studied the rate and duration of sonographically detectable clip detectability in patients with breast cancer who had sonographically detectable clips inserted over a 2-year period. Nine of 26 patients had neoadjuvant chemotherapy, with all clips remaining detectable 140 to 187 days after insertion. Six of the 9 had intraoperative sonographic localization, with 1 reoperation (17%). Eleven additional patients with nonpalpable tumors and sonographically detectable clips had intraoperative sonographic localization with 1 reoperation (9%). In 1 patient, a sonographically detectable clip enabled intraoperative identification of a suspicious lymph node. There were no complications or clip migration. Sonographically detectable clips are helpful in breast cancer surgery with and without neoadjuvant chemotherapy, remaining detectable for many months and often averting preoperative localization and scheduling difficulties.

A randomized prospective study of lumpectomy margin assessment with use of MarginProbe in patients with nonpalpable breast malignancies.

BACKGROUND: The presence of tumor cells at the margins of breast lumpectomy specimens is associated with an increased risk of ipsilateral tumor recurrence. Twenty to 30 % of patients undergoing breast-conserving surgery require second procedures to achieve negative margins. This study evaluated the adjunctive use of the MarginProbe device (Dune Medical Devices Ltd, Caesarea, Israel) in providing real-time intraoperative assessment of lumpectomy margins. METHODS: This multicenter randomized trial enrolled patients with nonpalpable breast malignancies. The study evaluated MarginProbe use in addition to standard intraoperative methods for margin assessment. After specimen removal and inspection, patients were randomized to device or control arms. In the device arm, MarginProbe was used to examine the main lumpectomy specimens and direct additional excision of positive margins. Intraoperative imaging was used in both arms; no intraoperative pathology assessment was permitted. RESULTS: In total, 596 patients were enrolled. False-negative rates were 24.8 and 66.1 % and false-positive rates were 53.6 and 16.6 % in the device and control arms, respectively. All positive margins on positive main specimens were resected in 62 % (101 of 163) of cases in the device arm, versus 22 % (33 of 147) in the control arm (p < 0.001). A total of 19.8 % (59 of 298) of patients in the device arm underwent a reexcision procedure compared with 25.8 % (77 of 298) in the control arm (6 % absolute, 23 % relative reduction). The difference in tissue volume removed was not significant. CONCLUSIONS: Adjunctive use of the MarginProbe device during breast-conserving surgery improved surgeons' ability to identify and resect positive lumpectomy margins in the absence of intraoperative pathology assessment, reducing the number of patients requiring reexcision. MarginProbe may aid performance of breast-conserving surgery by reducing the burden of reexcision procedures for patients and the health care system.

Ipsilateral hemodialysis access after axillary dissection for breast cancer.

Breast cancer survivors who have had axillary lymph node dissection (ALND) and who later develop end-stage renal failure may eventually require hemodialysis access. If veins available for access in the contralateral arm have been exhausted, especially after chemotherapy, the ipsilateral arm will have to be considered for access construction. There are no evidence-based guidelines for lymphedema prevention, but there are sweeping recommendations to avoid physical injury to the ipsilateral limb, including needle puncture, after ALND with or without radiotherapy. Three studies have shown little or no effect of hand surgery in producing or exacerbating lymphedema after ALND. Dialysis access guidelines recommend the use of autogenous accesses over synthetic grafts whenever possible. Three patients after ALND were referred for hemodialysis access construction in our center. Pre-operative duplex ultrasound confirmed that patent veins appropriate for autogenous access construction were only present in the ipsilateral arm. Autogenous arteriovenous fistulas were constructed in the ipsilateral arm in the three patients. All the three entered our access surveillance program and were regularly examined. All had more than 20 lymph nodes removed. One had axillary radiotherapy and anthracycline-based chemotherapy, one had anthracycline-based chemotherapy without axillary radiotherapy and one had neither treatment. The access was established 4-10 years after ALND. No patient developed significant lymphedema at two, 20 and 76 months respectively after access construction, with cannulation for dialysis occurring three times a week. Autogenous hemodialysis access construction does not seem to contribute to lymphedema development after ALND. Physicians and other medical personnel caring for patients with breast cancer should not oppose the use of the ipsilateral arm if it is the only arm with vasculature suitable for autogenous access construction. Recommendations for lymphedema prevention may exaggerate the extent of risk attributable to interventions in the ipsilateral arm.

Hybrid Prepectoral Direct-to-Implant and Autologous Fat Graft Simultaneously in Immediate Breast Reconstruction: A Single Surgeon's Experience with 25 Breasts in 15 Consecutive Cases.

BACKGROUND: The direct-to-implant method depends on the quality of the mastectomy flaps and can be used only when the flaps are adequately perfused. Even though the method was designed to be a definitive reconstruction procedure, it has been associated with an increased likelihood that additional operative revision will be required in order to achieve the expected final cosmetic outcome. The authors describe a hybrid prepectoral direct-to-implant method that combines autologous fat grafting in the superior medial pole with immediate reconstruction. METHODS: In this prospective study, 15 patients (25 reconstructed breasts) underwent simultaneous hybrid prepectoral direct-to-implant reconstruction together with autologous fat grafting performed by a single senior plastic surgeon (Y.G). RESULTS: The mean quantity of autologous fat grafted in the superior medial aspect of the breast was 59.4 ± 12.8 cc. The mean total volume of the hybrid reconstructed breast, including implant and autologous fat graft, was 497.2 ± 89.1 cc. Satisfying final outcomes were achieved in all cases. There were no major complications, although minor complications were observed. CONCLUSIONS: The authors' hybrid approach allows the surgeon to achieve a more satisfying outcome with regard to the cleavage area. It results in a better natural appearance, an improved contour, and reduced upper pole rippling and deflation, with a lower likelihood that an additional operative revision will be required to achieve the desired final aesthetic outcome. The authors believe that their hybrid approach should be implemented as an integral part of the direct-to-implant prepectoral reconstruction procedure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Oncoplastic breast consortium recommendations for mastectomy and whole breast reconstruction in the setting of post-mastectomy radiation therapy.

AIM: Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. METHODS: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. RESULTS: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. CONCLUSIONS: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR.

Resection margins in ultrasound-guided breast-conserving surgery.

BACKGROUND: Few published studies have shown the benefits of intraoperative ultrasound in avoiding inadequate margins in breast-conserving surgery. The aim of this study is to quantify intraoperative ultrasound margin size and assess its relationship to tumor size, multifocality, palpability, histology, and presence of intraductal component. METHODS: Patients with breast cancer undergoing breast-conserving surgery in whom the operating surgeon visualized the tumor by ultrasound were included. Ultrasound margins measured intraoperatively were prospectively recorded and compared with pathology margins. RESULTS: Forty-five patients with 48 tumors were included. Twenty five patients (56%) had palpable tumors. Pathologic mean tumor size was 1.9 cm [95% confidence interval (CI) 1.6-2.2 cm, range 0.5-4.8 cm]. There was good correlation between closest margins recorded by ultrasound and pathology margins (r = 0.4674, P < 0.0008). Fourteen patients (31%) had margins re-excised intraoperatively, 12 of them in the direction of the closest pathological margin. Three patients (7%), all of whom had intraoperative re-excision, had a second operation for involved margins without residual cancer on pathological examination of the reoperative specimens. Ultrasound margins ≥0.5 cm achieved adequate pathology margins of ≥0.2 cm in 95% of margins. Overestimation of pathology margins by ultrasound measurement was significantly affected by multifocality (P = 0.0473). Tumor size, palpability, invasive lobular histology, and presence of ductal carcinoma in situ (DCIS) did not cause significant overestimation of pathology margins by ultrasound. CONCLUSIONS: Intraoperative ultrasound may help maintain a low level of reoperation after breast-conserving surgery. Ultrasound margins <0.5 cm should be re-excised intraoperatively. Reliability of ultrasound in predicting the closest pathology margins was diminished in patients with multifocal tumors.

Investigation of the Association between Drinking Water Habits and the Occurrence of Women Breast Cancer.

Risk and protective factors for breast cancer (BC) include lifestyle, diet, reproduction, and others. Increased risk for colon cancer was linked with low water intake. The link between water consumption and BC was scarcely studied. We investigated the association between water and fluid consumption and the occurrence of BC in a retrospective case-control study in the Shaare Zedek Medical Center, Jerusalem, in 206 women aged 25-65 years (106 with newly diagnosed BC, and 100 controls). A food frequency questionnaire (FFQ), consumption of water, foods, and beverages, lifestyle, and other risk and protective factors were recorded. The age of women in both groups was comparable ((M ± SD) 52.7 ± 9.8 and 50.6 ± 11.4 years, respectively (p = 0.29)). Women with BC consumed 20.2% less water (M ± SD = 5.28 ± 4.2 and 6.62 ± 4.5 cups/day, respectively, p = 0.02) and 14% less total fluids than controls (M ± SD = 2095 ± 937 mL/day and 2431 ± 1087 mL/day, respectively, p = 0.018). Multiple stepwise logistic regression showed that the differences remained significant both for daily water consumption (p = 0.031, CI = 0.462-0.964) and for total daily liquid intake (p = 0.029, CI = 0.938-0.997). Low water and liquids intake as a risk factor for BC may be related to the younger age of our subjects. The effect of age on the potential role of water intake in decreasing BC risk should be investigated.

Clinical implications of contralateral axillary sentinel lymph nodes.

Extra-axillary sentinel lymph nodes can only be detected if radioactive tracer is used and pre-operative scans are carried out. The presence of metastatic sentinel lymph nodes in most extra-axillary sites will upstage patients if the ipsilateral axillary sentinel lymph node is normal. Paradoxically, the presence of metastatic sentinel lymph nodes in the contralateral axilla has the potential to prevent upstaging to stage IV, but only if detected as a sentinel node at the initial surgery rather than as a systemic recurrence at some later time. We describe a case of bilateral axillary sentinel lymph nodes detected by pre-operative lymphoscintigraphy in a patient with a medial quadrant breast cancer and discuss the possible implications of such a finding.

Increased mammographic screening and use of percutaneous image-guided core biopsy in non-palpable breast cancer: impact on surgical treatment.

BACKGROUND: Major efforts are being directed at the early diagnosis of breast cancer. The diagnosis rate of non-palpable tumors is steadily growing as a result of increased screening by mammography. In most patients with non-palpable lesions, percutaneous image-guided biopsies have replaced wire localization with surgical excision for obtaining tissue diagnosis. In recent years the Israel Ministry of Health initiated a mammograpy screening program. Percutaneous image-guided biopsies have also become widely available. OBJECTIVE: To assess the impact of these changes on breast cancer surgical treatment in our hospital. METHODS: The charts of 483 patients operated on in our department for primary breast carcinoma during the years 1997 to mid-2001 were reviewed. Data on the mode of diagnosis, tumor stage, resection margins, and number and types of operations were recorded and analyzed. The term non-palpable tumors relates to tumors necessitating wire localization for surgical excision. RESULTS: The percentage of patients diagnosed with non-palpable tumors rose from 16.2% in 1997 to 47.4% in 2001, with an average size of 2.6 cm for palpable and 1.7 cm for non-palpable tumors. The rate of preoperative diagnosis for non-palpable tumors rose from 6.2% in 1997 to 96.4% in 2001. The rate of involved or very close margins was reduced by 73% in the patient group diagnosed preoperatively as compared to those without a preoperative diagnosis (10.6% vs. 39.4%). Finally, the percentage of patients who had two operations fell from 56.2% in 1997 to 11.1% in 2001. CONCLUSIONS: The mammography screening program in Jerusalem in 1997-2001 was effective in increasing the relative percentage of non-palpable breast cancers with reduced tumor size at diagnosis. The improved availability of preoperative tissue diagnosis in these patients reduced the number of surgical procedures needed.

A prospective, randomized, controlled, multicenter study of a real-time, intraoperative probe for positive margin detection in breast-conserving surgery.

BACKGROUND: This randomized, double-arm trial was designed to study the benefit of a novel device (MarginProbe, Dune Medical Devices, Caesarea, Israel) in intraoperative margin assessment for breast-conserving surgery (BCS) and the associated reduction in reoperations. METHODS: In the device group, the probe was applied to the lumpectomy specimen and additional tissue was excised according to device readings. Study arms were compared by reoperation rates and by correct surgical reaction confirmed by histology. RESULTS: Three hundred patients were enrolled. Device use was associated with improved correct surgical reaction, defined as additional re-excision in all histologically detected positive margins, with tumor within 1 mm of inked margin. The repeat lumpectomy rate was significantly reduced by 56% in the device arm: 5.6% versus 12.7% in the control arm. There were no differences in excised tissue volume or cosmetic outcome. CONCLUSIONS: Intraoperative use of the MarginProbe for positive margin detection is safe and effective in BCS and decreases the rate of repeat operations.

Preoperative lymphatic mapping does not predict the number of axillary sentinel lymph nodes identified during surgery in breast cancer patients.

Sentinel lymph node biopsy (SLNB) has become the standard of care in most centers for axillary staging in patients with early breast cancer. Multiple radioactive nodes are often identified at surgery. The finding of multiple sentinel lymph nodes (SLNs) has been shown to be associated with lower rates of false-negative results in the SLNB procedure, hence the importance of removing and examining all SLNs. Often preoperative lymphatic mapping (PLM) is performed prior to surgery. In this study we examined whether the exact number of SLNs identified during surgery can be accurately predicted by PLM. During the years 2001-2004, 155 patients underwent both PLM and a SLNB in our breast unit. During surgery, an attempt was made to remove all radioactive nodes. The number of axillary radioactive foci found on PLM was compared with the number of radioactive nodes identified during surgery. The average number of sentinel nodes harvested was 2.3 (range 1-9). The average number of radioactive foci identified on PLM was 1.8 (range 0-5). Of the 155 patients, the number of sentinel nodes retrieved in surgery was greater than that found in preoperative mapping in 65 patients (41.9%), equal to that found in preoperative mapping in 60 patients (38.7%), and less than that found in preoperative mapping in 30 patients (19.4%). Thus in most patients, the number of SLNs found on PLM did not reflect the number of SLNs found intraoperatively. Therefore, even when the number of nodes identified on PLM has been reached in surgery, a meticulous search for additional nodes should still be carried out. The number of hot spots in preoperative mapping should serve as a rough indicator of the smallest number of nodes the surgeon should attempt to resect, but not the exact number of nodes expected to be found.

Intraoperative palpation for clinically suspicious axillary sentinel lymph nodes reduces the false-negative rate of sentinel lymph node biopsy in breast cancer.

Axillary sentinel lymph node biopsy (SLNB) is widely used to identify the first lymph node draining breast tumors. When the sentinel lymph node is free of metastasis, axillary dissection is avoided because the rest of the nodes are expected to be negative as well. A false-negative rate of 5% is considered acceptable. In the case of a false-negative SLNB, adjuvant local and systemic treatments might be suboptimal. We assessed the effect of intraoperative axillary palpation for clinically suspicious lymph nodes that are not otherwise detected by radioactive tracer or blue dye on the false-negative rate of SLNB in breast cancer patients. Our prospective database of patients having surgery for primary invasive breast cancer and who had a SLNB from 2000 to 2004 was reviewed. Only patients with clinically negative nodes preoperatively were included. The procedure included preoperative injection of radiotracer, with dye injection as backup, and intraoperative palpation of the axilla for suspicious lymph nodes that were not radioactive or blue. Of the 290 patients, 89 (30.7%) had sentinel node involvement by tumor. Seven patients had clinically suspicious nodes identified solely by palpation and not by tracer, in addition to sentinel lymph nodes detected by tracer. In five of the seven patients, the nodes harbored metastasis. In four of these five patients (4.5% of the 89 patients with axillary involvement), the palpable nodes were the only ones involved. A generous axillary incision and systematic palpation of the axilla reduces the false-negative rate and should be a part of the SLNB procedure.

The "Sentinel Chain": a new concept for prediction of axillary node status in breast cancer patients.

BACKGROUND AND OBJECTIVES: More than half the breast cancer patients with positive sentinel lymph nodes (SLN) do not harbor additional metastases in non-sentinel nodes (NSN). The aim of this study was to identify a subgroup of patients with positive SLNs and negative NSNs, on the basis of tumor involvement patterns in multiple radioactive nodes. METHODS: Between 2000 and 2004, 290 patients with primary invasive breast cancer and clinically negative axillary nodes had a SLN biopsy in our breast unit. Radiotracer was identified intraoperatively in the axilla. All radioactive nodes were removed and radioactivity was measured in each node extracorporeally. Nodes were ranked according to radioactivity, constituting a "Sentinel Chain", and the histopathological status of each node was reported. The different metastatic involvement patterns of the Sentinel Chain were correlated with the metastatic status of the NSNs after axillary dissection. Information was charted in a prospective database. RESULTS: Of 290 patients, 216 (74.5%) had multiple radioactive nodes. Ninety patients (31%) had SLN metastases. Fifty patients had multiple ranked radioactive nodes and positive SLNs. Twenty-five of these patients had a sequential involvement pattern, with tumor-bearing high radioactivity nodes, and uninvolved low-radioactivity nodes. In the 23 of these 25 patients who had axillary dissection, NSN involvement was detected in only one patient (4.3%), whereas in 24 patients with other involvement patterns of the Sentinel Chain, NSN involvement reached 54.2% (p<0.001). CONCLUSION: Tumor-free status of NSN may be predicted using the Sentinel Chain concept in some breast cancer patients with positive SLNs.